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Sample records for potential oral delivery

  1. Evaluating the potential of cubosomal nanoparticles for oral delivery of amphotericin B in treating fungal infection

    Directory of Open Access Journals (Sweden)

    Yang Z

    2014-01-01

    Full Text Available Zhiwen Yang,1,3 Meiwan Chen,2 Muhua Yang,1 Jian Chen,1 Weijun Fang,1 Ping Xu11Department of Pharmacy, Songjiang Hospital Affiliated The First People's Hospital, Shanghai Jiao Tong University, Shanghai, 2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, 3Shanghai Songjiang Hospital Affiliated Nanjing Medical University, Nanjing, People's Republic of ChinaAbstract: The oral administration of amphotericin B (AmB has a major drawback of poor bioavailability. The aim of this study was to investigate the potential of glyceryl monoolein (GMO cubosomes as lipid nanocarriers to improve the oral efficacy of AmB. Antifungal efficacy was determined in vivo in rats after oral administration, to investigate its therapeutic use. The human colon adenocarcinoma cell line (Caco-2 was used in vitro to evaluate transport across a model of the intestinal barrier. In vivo antifungal results showed that AmB, loaded in GMO cubosomes, could significantly enhance oral efficacy, compared against Fungizone®, and that during a 2 day course of dosage 10 mg/kg the drug reached effective therapeutic concentrations in renal tissue for treating fungal infections. In the Caco-2 transport studies, GMO cubosomes resulted in a significantly larger amount of AmB being transported into Caco-2 cells, via both clathrin- and caveolae-mediated endocytosis, but not macropinocytosis. These results suggest that GMO cubosomes, as lipid nanovectors, could facilitate the oral delivery of AmB.Keywords: glyceryl monoolein cubosomes, oral delivery, amphotericin B, antifungal activity, absorption mechanism

  2. Potential of insulin nanoparticle formulations for oral delivery and diabetes treatment.

    Science.gov (United States)

    Wong, Chun Y; Al-Salami, Hani; Dass, Crispin R

    2017-10-28

    Nanoparticles have demonstrated significant advancements in potential oral delivery of insulin. In this publication, we review the current status of polymeric, inorganic and solid-lipid nanoparticles designed for oral administration of insulin. Firstly, the structure and physiological function of insulin are examined. Then, the efficiency and shortcomings of insulin nanoparticle are discussed. These include the susceptibility to digestive enzyme degradation, instability in the acidic pH environment, poor mucus diffusion and inadequate permeation through the gastrointestinal epithelium. In order to optimise the nanocarriers, the following considerations, including polymer nature, surface charge, size, polydispersity index and morphology of nanoparticles, have to be taken into account. Some novel designs such as chitosan-based glucose-responsive nanoparticles, layer by layer technique-based nanoparticles and zwitterion nanoparticles are being adopted to overcome the physiological challenges. The review ends with some future directions and challenges to be addressed for the success of oral delivery of insulin-loaded nanoparticle formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Biotinylated liposomes as potential carriers for the oral delivery of insulin.

    Science.gov (United States)

    Zhang, Xingwang; Qi, Jianping; Lu, Yi; He, Wei; Li, Xiaoyang; Wu, Wei

    2014-01-01

    This study aimed to explore biotinylated liposomes (BLPs) as novel carriers to enhance the oral delivery of insulin. Biotinylation was achieved by incorporating biotin-conjugated phospholipids into the liposome membranes. A significant hypoglycemic effect and enhanced absorption were observed after treating diabetic rats with the BLPs with a relative bioavailability of 12.09% and 8.23%, based on the measurement of the pharmacologic effect and the blood insulin level, respectively; this achieved bioavailability was approximately double that of conventional liposomes. The significance of the biotinylation was confirmed by the facilitated absorption of the BLPs through receptor-mediated endocytosis, as well as by the improved physical stability of the liposomes. Increased cellular uptake and quick gastrointestinal transport further verified the ability of the BLPs to enhance absorption. These results provide a proof of concept that BLPs can be used as potential carriers for the oral delivery of insulin. Diabetes remains a major source of mortality in the Western world, and advances in its management are expected to have substantial socioeconomic impact. In this paper, biotinylated liposomes were utilized as carriers of insulin for local delivery, demonstrating the feasibility of this approach in a rat model. © 2014.

  4. Self-nanoemulsifying drug delivery systems for oral insulin delivery

    DEFF Research Database (Denmark)

    Li, Ping; Tan, Angel; Prestidge, Clive A

    2014-01-01

    This study aims at evaluating the combination of self-nanoemulsifying drug delivery systems (SNEDDS) and enteric-coated capsules as a potential delivery strategy for oral delivery of insulin. The SNEDDS preconcentrates, loaded with insulin-phospholipid complex at different levels (0, 2.5 and 10% w...

  5. Biomimetic insulin-imprinted polymer nanoparticles as a potential oral drug delivery system

    Directory of Open Access Journals (Sweden)

    Paul Pijush Kumar

    2017-06-01

    Full Text Available In this study, we investigate molecularly imprinted polymers (MIPs, which form a three-dimensional image of the region at and around the active binding sites of pharmaceutically active insulin or are analogous to b cells bound to insulin. This approach was employed to create a welldefined structure within the nanospace cavities that make up functional monomers by cross-linking. The obtained MIPs exhibited a high adsorption capacity for the target insulin, which showed a significantly higher release of insulin in solution at pH 7.4 than at pH 1.2. In vivo studies on diabetic Wistar rats showed that the fast onset within 2 h is similar to subcutaneous injection with a maximum at 4 h, giving an engaged function responsible for the duration of glucose reduction for up to 24 h. These MIPs, prepared as nanosized material, may open a new horizon for oral insulin delivery.

  6. Potential benefits of chewing gum for the delivery of oral therapeutics and its possible role in oral healthcare

    NARCIS (Netherlands)

    Wessel, Stefan W.; van der Mei, Henny C.; Maitra, Amarnath; Dodds, Michael W. J.; Busscher, Henk J.

    2016-01-01

    Introduction: Over the years, chewing gum has developed from a candy towards an oral health-promoting nutraceutical. This review summarizes evidence for the oral health benefits of chewing gum, emphasizing identification of active ingredients in gum that facilitate prevention and removal of oral

  7. Oral delivery of anticancer drugs

    DEFF Research Database (Denmark)

    Thanki, Kaushik; Gangwal, Rahul P; Sangamwar, Abhay T

    2013-01-01

    The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes improvement in quality of life of patients and reduced health care costs. Subsequently, the challenges...... incurred in the oral delivery of anticancer agents have been especially emphasized. Sincere efforts have been made to compile the various physicochemical properties of anticancer drugs from either literature or predicted in silico via GastroPlus™. The later section of the paper reviews various emerging...... trends to tackle the challenges associated with oral delivery of anticancer drugs. These invariably include efflux transporter based-, functional excipient- and nanocarrier based-approaches. The role of drug nanocrystals and various others such as polymer based- and lipid based...

  8. Floating Microparticulate Oral Diltiazem Hydrochloride Delivery ...

    African Journals Online (AJOL)

    Delivery System for Improved Delivery to Heart ... Conclusion: Microparticulate floating (gastroretentive) oral drug delivery system of diltiazem prepared ..... treatment of cardiac disease. ... hydrochloride-loaded mucoadhesive microspheres.

  9. Lipid-based oral delivery systems for skin deposition of a potential chemopreventive DIM derivative: characterization and evaluation.

    Science.gov (United States)

    Boakye, Cedar H A; Patel, Ketan; Patel, Apurva R; Faria, Henrique A M; Zucolotto, Valtencir; Safe, Stephen; Singh, Mandip

    2016-10-01

    The objective of this study was to explore the oral route as a viable potential for the skin deposition of a novel diindolylmethane derivative (DIM-D) for chemoprevention activity. Various lipid-based oral delivery systems were optimized and compared for enhancing DIM-D's oral bioavailability and skin deposition. Preformulation studies were performed to evaluate the log P and solubility of DIM-D. Microsomal metabolism, P-glycoprotein efflux, and caco-2 monolayer permeability of DIM-D were determined. Comparative evaluation of the oral absorption and skin deposition of DIM-D-loaded various lipid-based formulations was performed in rats. DIM-D showed pH-dependent solubility and a high log P value. It was not a strong substrate of microsomal degradation and P-glycoprotein. SMEDDs comprised of medium chain triglycerides, monoglycerides, and kolliphor-HS15 (36.70 ± 0.42 nm). SNEDDs comprised of long chain triglycerides, cremophor RH40, labrasol, and TPGS (84.00 ± 14.14 nm). Nanostructured lipid carriers (NLC) consisted of compritol, miglyol, and surfactants (116.50 ± 2.12 nm). The blank formulations all showed >70 % cell viability in caco-2 cells. Differential Scanning Calorimetry confirmed the amorphization of DIM-D within the lipid matrices while Atomic Force Microscopy showed particle size distribution similar to the dynamic light scattering data. DIM-D also showed reduced permeation across caco-2 monolayer that was enhanced (p < 0.05) by SNEDDs in comparison to SMEDDs and NLC. Fabsolute for DIM-D SNEDDs, SMEDDs, and NLC was 0.14, 0.04, and 0.007, respectively. SNEDDs caused 53.90, 11.32, and 15.08-fold more skin deposition of DIM-D than the free drug, SMEDDs, and NLC, respectively, at 2 h following oral administration and shows a viable potential for use in skin cancer chemoprevention. Graphical Abstract ᅟ.

  10. Oral transmucosal delivery of naratriptan.

    Science.gov (United States)

    Sattar, Mohammed; Lane, Majella E

    2016-11-30

    Naratriptan (NAR) is currently used as the hydrochloride salt (NAR.HCl) for the treatment of migraine and is available in tablet dosage forms for oral administration. Buccal drug delivery offers a number of advantages compared with conventional oral delivery including rapid absorption, avoidance of first pass metabolism and improved patient compliance. We have previously prepared and characterised the base form of NAR and shown that it has more favourable properties for buccal delivery compared with NAR.HCl. This study describes the design and evaluation of a range of formulations for oral transmucosal delivery of NAR base. Permeation studies were conducted using excised porcine buccal tissue mounted in Franz cells. Of the neat solvents examined, Transcutol ® P (TC) showed the greatest enhancement effects and was the vehicle in which NAR was most soluble. The mechanisms by which TC might promote permeation were further probed using binary systems containing TC with either buffer or Miglyol 812 ® (MG). Mass balance studies were also conducted for these systems. The permeation of TC as well as NAR was also monitored for TC:MG formulations. Overall, TC appears to promote enhanced membrane permeation of NAR because of its rapid uptake into the buccal tissue. Synergistic enhancement of buccal permeation was observed when TC was combined with MG and this is attributed to the increased thermodynamic activity of NAR in these formulations. Significantly enhanced permeation of NAR was achieved for TC:MG and this was also associated with less TC remaining on the tissue or in the tissue at the end of the experiment. To our knowledge this is the first report where both enhancer and active have been monitored in buccal permeation studies. The findings underline the importance of understanding the fate of vehicle components for rational formulation design of buccal delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Oral and transdermal DL-methylphenidate-ethanol interactions in C57BL/6J mice: potentiation of locomotor activity with oral delivery.

    Science.gov (United States)

    Bell, Guinevere H; Griffin, William C; Patrick, Kennerly S

    2011-12-01

    Many abusers of dl-methylphenidate co-abuse ethanol. The present animal study examined behavioral effects of oral or transdermal DL-methylphenidate in combination with a high, depressive dose of ethanol to model co-abuse. Locomotor activity of C57BL/6J mice was recorded for 3 h following dosing with either oral DL-methylphenidate (7.5 mg/kg) or transdermal DL-methylphenidate (Daytrana®;1/4 of a 12.5 cm(2) patch; mean dose 7.5 mg/kg), with or without oral ethanol (3 g/kg). Brains were enantiospecifically analyzed for the isomers of methylphenidate and the transesterification metabolite ethylphenidate. An otherwise depressive dose of ethanol significantly potentiated oral DL-methylphenidate induced increases in total distance traveled for the first 100 min (pbrain D-methylphenidate concentrations were significantly elevated by ethanol in both the oral (65% increase) and transdermal (88% increase) groups. The corresponding L-ethylphenidate concentrations were 10 ng/g and 130 ng/g. Stimulant induced motor activity in rodents may correlate with abuse liability. Potentiation of DL-methylphenidate motor effects by concomitant ethanol carries implications regarding increased abuse potential of DL-methylphenidate when combined with ethanol. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Lipid drug conjugate nanoparticle as a potential nanocarrier for the oral delivery of pemetrexed diacid: Formulation design, characterization, ex vivo, and in vivo assessment.

    Science.gov (United States)

    Soni, Kriti; Mujtaba, Ali; Kohli, Kanchan

    2017-10-01

    The present work was to develop lipid drug conjugated (LDC) nanoparticles for the potential oral delivery of pemetrexed diacid (PTX) and evaluation of its in vitro, ex vivo and in vivo potentials. The LDC was prepared by salt formation of PTX with stearic acid and followed by cold homogenization technique to produce the LDC nanoparticles. FTIR analysis of LDC proved the presence of amide bond in LDC powder indicating the conjugation between drug and lipid. LDC nanoparticles was found to have particle size 121.9±1.85nm and zeta potential -51.6mV±1.23 and entrapment efficiency 81.0±0.89%. TEM images revealed spherical morphology and were in corroboration with particle size measurements. Ex vivo gut permeation studies revealed a very good enhancement in permeation of drug present in the LDC as compared to plain drug solution and were confirmed by CLSM. MTT assay conformed significant% toxicity at the end of 24h and 48h. Furthermore, the AUC 0-24 of PTX from the optimized LDC nanoparticels was found to be 4.22 folds higher than that from PTX suspension on oral administration. Thus, LDC has high potential for the oral delivery of PTX in cancer therapy and future prospects for the industrial purpose. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Synthetic surfactant- and cross-linker-free preparation of highly stable lipid-polymer hybrid nanoparticles as potential oral delivery vehicles.

    Science.gov (United States)

    Wang, Taoran; Xue, Jingyi; Hu, Qiaobin; Zhou, Mingyong; Chang, Chao; Luo, Yangchao

    2017-06-05

    The toxicity associated with concentrated synthetic surfactants and the poor stability at gastrointestinal condition are two major constraints for practical applications of solid lipid nanoparticles (SLN) as oral delivery vehicles. In this study, a synthetic surfactant-free and cross-linker-free method was developed to fabricate effective, safe, and ultra-stable lipid-polymer hybrid nanoparticles (LPN). Bovine serum albumin (BSA) and dextran varying in molecular weights were first conjugated through Maillard reaction and the conjugates were exploited to emulsify solid lipid by a solvent diffusion and sonication method. The multilayer structure was formed by self-assembly of BSA-dextran micelles to envelope solid lipid via a pH- and heating-induced facile process with simultaneous surface deposition of pectin. The efficiency of different BSA-dextran conjugates was systematically studied to prepare LPN with the smallest size, the most homogeneous distribution and the greatest stability. The molecular interactions were characterized by Fourier transform infrared and fluorescence spectroscopies. Both nano spray drying and freeze-drying methods were tested to produce spherical and uniform pectin-coated LPN powders that were able to re-assemble nanoscale structure when redispersed in water. The results demonstrated the promise of a synthetic surfactant- and cross-linker-free technique to prepare highly stable pectin-coated LPN from all natural biomaterials as potential oral delivery vehicles.

  14. Floating Microparticulate Oral Diltiazem Hydrochloride Delivery ...

    African Journals Online (AJOL)

    Purpose: To formulate and evaluate floating microparticulate oral diltiazem delivery system for possible delivery to the heart. Method: Floating microspheres were prepared using cellulose acetate and Eudragit RS100 polymers by emulsion solvent evaporation technique. The dried floating microspheres were evaluated for ...

  15. Oral transmucosal drug delivery for pediatric use.

    Science.gov (United States)

    Lam, Jenny K W; Xu, Yingying; Worsley, Alan; Wong, Ian C K

    2014-06-01

    The formulation of medicines for children remains a challenge. An ideal pediatric formulation must allow accurate dose administration and be in a dosage form that can be handled by the target age group. It is also important to consider the choices and the amount of excipients used in the formulation for this vulnerable age group. Although oral formulations are generally acceptable to most pediatric patients, they are not suitable for drugs with poor oral bioavailability or when a rapid clinical effect is required. In recent years, oral transmucosal delivery has emerged as an attractive route of administration for pediatric patients. With this route of administration, a drug is absorbed through the oral mucosa, therefore bypassing hepatic first pass metabolism and thus avoiding drug degradation or metabolism in the gastrointestinal tract. The high blood flow and relatively high permeability of the oral mucosa allow a quick onset of action to be achieved. It is a simple and non-invasive route of drug administration. However, there are several barriers that need to be overcome in the development of oral transmucosal products. This article aims to provide a comprehensive review of the current development of oral transmucosal delivery specifically for the pediatric population in order to achieve systemic drug delivery. The anatomical and physiological properties of the oral mucosa of infants and young children are carefully examined. The different dosage forms and formulation strategies that are suitable for young patients are discussed. © 2013.

  16. Thiolated chitosans: useful excipients for oral drug delivery.

    Science.gov (United States)

    Werle, Martin; Bernkop-Schnürch, Andreas

    2008-03-01

    To improve the bioavailability of orally administered drugs, formulations based on polymers are of great interest for pharmaceutical technologists. Thiolated chitosans are multifunctional polymers that exhibit improved mucoadhesive, cohesive and permeation-enhancing as well as efflux-pump-inhibitory properties. They can be synthesized by derivatization of the primary amino groups of chitosan with coupling reagents bearing thiol functions. Various data gained in-vitro as well as in-vivo studies clearly demonstrate the potential of thiolated chitosans for oral drug delivery. Within the current review, the synthesis and characterization of thiolated chitosans so far developed is summarized. Features of thiolated chitosans important for oral drug delivery are discussed as well. Moreover, different formulation approaches, such as matrix tablets and micro-/nanoparticles, as well as the applicability of thiolated chitosans for the oral delivery of various substance classes including peptides and efflux pump substrates, are highlighted.

  17. Graft Polymerization of Acryloyloxystarch with Poly(D,L-lactide) Macromonomer--A Potential Drug Delivery Carrier for Oral Administration

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ Starch is the second largest natural biopolymer. Its unique biodegradable and biocompatible properties make it be increasingly applied to the field of biomedicine[1~4]. As one kind of polysaccharide, starch is easily degraded into small organic molecules by amylase in the alimentary canal. The fact that the activity of amylase is restrained in the high acid environment in stomach provides an opportunity to prepare an intestinal-specific delivery carrier with starch. In order to protect the drugs that are sensitive to the enzyms in alimentary canal, a hydrophobic layer should be constructed between the outer bioadhensive shell and the drug.

  18. Oral insulin delivery: existing barriers and current counter-strategies.

    Science.gov (United States)

    Gedawy, Ahmed; Martinez, Jorge; Al-Salami, Hani; Dass, Crispin R

    2018-02-01

    The chronic and progressive nature of diabetes is usually associated with micro- and macrovascular complications where failure of pancreatic β-cell function and a general condition of hyperglycaemia is created. One possible factor is failure of the patient to comply with and adhere to the prescribed insulin due to the inconvenient administration route. This review summarizes the rationale for oral insulin administration, existing barriers and some counter-strategies trialled. Oral insulin mimics the physiology of endogenous insulin secreted by pancreas. Following the intestinal absorption of oral insulin, it reaches the liver at high concentration via the portal vein. Oral insulin on the other hand has the potential to protect pancreatic β-cells from autoimmune destruction. Structural modification, targeting a particular tissue/receptor, and the use of innovative pharmaceutical formulations such as nanoparticles represent strategies introduced to improve oral insulin bioavailability. They showed promising results in overcoming the hurdles facing oral insulin delivery, although delivery is far from ideal. The use of advanced pharmaceutical technologies and further research in particulate carrier system delivery predominantly nanoparticle utilization would offer useful tools in delivering insulin via the oral route which in turn would potentially improve diabetic patient compliance to insulin and the overall management of diabetes. © 2017 Royal Pharmaceutical Society.

  19. Concanavalin A conjugated biodegradable nanoparticles for oral insulin delivery

    Science.gov (United States)

    Hurkat, Pooja; Jain, Aviral; Jain, Ashish; Shilpi, Satish; Gulbake, Arvind; Jain, Sanjay K.

    2012-11-01

    Major research issues in oral protein delivery include the stabilization of protein in delivery devices which could increase its oral bioavailability. The study deals with development of oral insulin delivery system utilizing biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and modifying its surface with Concanavalin A to increase lymphatic uptake. Surface-modified PLGA nanoparticles were characterized for conjugation efficiency of ligand, shape and surface morphology, particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro drug release. Stability of insulin in the developed formulation was confirmed by SDS-PAGE, and integrity of entrapped insulin was assessed using circular dichroism spectrum. Ex vivo study was performed on Wistar rats, which exhibited the higher intestinal uptake of Con A conjugated nanoparticles. In vivo study performed on streptozotocin-induced diabetic rats which indicate that a surface-modified nanoparticle reduces blood glucose level effectively within 4 h of its oral administration. In conclusion, the present work resulted in successful production of Con A NPs bearing insulin with sustained release profile, and better absorption and stability. The Con A NPs showed high insulin uptake, due to its relative high affinity for non-reducing carbohydrate residues i.e., fucose present on M cells and have the potential for oral insulin delivery in effective management of Type 1 diabetes condition.

  20. Concanavalin A conjugated biodegradable nanoparticles for oral insulin delivery

    Energy Technology Data Exchange (ETDEWEB)

    Hurkat, Pooja; Jain, Aviral; Jain, Ashish; Shilpi, Satish; Gulbake, Arvind; Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour Vishwavidyalaya, Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2012-11-15

    Major research issues in oral protein delivery include the stabilization of protein in delivery devices which could increase its oral bioavailability. The study deals with development of oral insulin delivery system utilizing biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and modifying its surface with Concanavalin A to increase lymphatic uptake. Surface-modified PLGA nanoparticles were characterized for conjugation efficiency of ligand, shape and surface morphology, particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro drug release. Stability of insulin in the developed formulation was confirmed by SDS-PAGE, and integrity of entrapped insulin was assessed using circular dichroism spectrum. Ex vivo study was performed on Wistar rats, which exhibited the higher intestinal uptake of Con A conjugated nanoparticles. In vivo study performed on streptozotocin-induced diabetic rats which indicate that a surface-modified nanoparticle reduces blood glucose level effectively within 4 h of its oral administration. In conclusion, the present work resulted in successful production of Con A NPs bearing insulin with sustained release profile, and better absorption and stability. The Con A NPs showed high insulin uptake, due to its relative high affinity for non-reducing carbohydrate residues i.e., fucose present on M cells and have the potential for oral insulin delivery in effective management of Type 1 diabetes condition.

  1. Transmembrane transport of peptide type compounds: prospects for oral delivery

    Science.gov (United States)

    Lipka, E.; Crison, J.; Amidon, G. L.

    1996-01-01

    Synthesis and delivery of potential therapeutic peptides and peptidomimetic compounds has been the focus of intense research over the last 10 years. While it is widely recognized that numerous limitations apply to oral delivery of peptides, some of the limiting factors have been addressed and their mechanisms elucidated, which has lead to promising strategies. This article will briefly summarize the challenges, results and current approaches of oral peptide delivery and give some insight on future strategies. The barriers determining peptide bioavailability after oral administration are intestinal membrane permability, size limitations, intestinal and hepatic metabolism and in some cases solubility limitations. Poor membrane permeabilities of hydrophilic peptides might be overcome by structurally modifying the compounds, thus increasing their membrane partition characteristics and/or their affinity to carrier proteins. Another approach is the site-specific delivery of the peptide to the most permeable parts of the intestine. The current view on size limitation for oral drug delivery has neglected partition considerations. Recent studies suggest that compounds with a molecular weight up to 4000 might be significantly absorbed, assuming appropriate partition behavior and stability. Metabolism, probably the most significant factor in the absorption fate of peptides, might be controlled by coadministration of competitive enzyme inhibitors, structural modifications and administration of the compound as a well absorbed prodrug that is converted into the therapeutically active agent after its absorption. For some peptides poor solubility might present a limitation to oral absorption, an issue that has been addressed by mechanistically defining and therefore improving formulation parameters. Effective oral peptide delivery requires further development in understanding these complex mechanisms in order to maximize the therapeutic potential of this class of compounds.

  2. Submicron Emulsions and Their Applications in Oral Delivery.

    Science.gov (United States)

    Mundada, Veenu; Patel, Mitali; Sawant, Krutika

    2016-01-01

    A "submicron emulsion" is an isotropic mixture of drug, lipids, and surfactants, usually with hydrophilic cosolvents and with droplet diameters ranging from 10 to 500 nm. Submicron emulsions are of increasing interest in medicine due to their kinetic stability, high solubilizing capacity, and tiny globule size. Because of these properties, they have been applied in various fields, such as personal care, cosmetics, health care, pharmaceuticals, and agrochemicals. Submicron emulsions are by far the most advanced nanoparticulate systems for the systemic delivery of biologically active agents for controlled drug delivery and targeting. They are designed mainly for pharmaceutical formulations suitable for various routes of administration like parenteral, ocular, transdermal, and oral. This review article describes the marked potential of submicron emulsions for oral drug delivery owing to their numerous advantages like reduced first pass metabolism, inhibition of P-glycoprotein efflux system, and enhanced absorption via intestinal lymphatic pathway. To overcome the limitations of liquid dosage forms, submicron emulsions can be formulated into solid dosage forms such as solid self-emulsifying systems. This article covers various types of submicron emulsions like microemulsion, nanoemulsion, and self-emulsifying drug delivery system (SEDDS), and their potential pharmaceutical applications in oral delivery with emphasis on their advantages, limitations, and advancements.

  3. Novel engineered systems for oral, mucosal and transdermal drug delivery.

    Science.gov (United States)

    Li, Hairui; Yu, Yuan; Faraji Dana, Sara; Li, Bo; Lee, Chi-Ying; Kang, Lifeng

    2013-08-01

    Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.

  4. Loading of microcontainers for oral drug delivery

    DEFF Research Database (Denmark)

    Marizza, Paolo

    The pharmaceutical research is facing several obstacles in the development of drug products for the oral delivery. The main problem deals with the intrinsic chemical nature of the new drug candidates, which are often poorly soluble and barely absorbed in the gastro-intestinal tract. Furthermore......, they are usually degraded before they are absorbed. These combined factors considerably reduce the bioavailability of many active ingredients. Several strategies have been developed to overcome these challenges. One of them are microfabricated drug delivery devices. Microreservoir based-systems are characterized...... of UV photolithography was developed. The fabrication of polymer patterns was optimized and loading with both small hydrophobic drugs and proteins was demonstrated. Finally, structural properties of hydrogels were elucidated by rheology and NMR with the perspective of controlling the drug release...

  5. Polymeric Micro- and Nanofabricatced Devices for Oral Drug Delivery

    Science.gov (United States)

    Fox, Cade Brylee

    While oral drug administration is by far the most preferred route, it is accompanied by many barriers that limit drug uptake such as the low pH of the stomach, metabolic and proteolytic enzymes, and limited permeability of the intestinal epithelium. As a result, many drugs ranging from small molecules to biological therapeutics have limited oral bioavailability, precluding them from oral administration. To address this issue, microfabrication has been applied to create planar, asymmetric devices capable of binding to the lining of the gastrointestinal tract and releasing drug at high concentrations, thereby increasing oral drug uptake. While the efficacy of these devices has been validated in vitro and in vivo, modifying their surfaces with nanoscale features has potential to refine their properties for enhanced drug delivery. This dissertation first presents an approach to fabricate polymeric microdevices coated with nanowires in a rapid, high throughput manner. The nanowires demonstrate rapid drug localization onto the surface of these devices via capillary action and increased adhesion to epithelial tissue, suggesting that this fabrication technique can be used to create devices with enhanced properties for oral drug delivery. Also presented are microdevices sealed with nanostraw membranes. The nanostraw membranes provide sustained drug release by limiting drug efflux from the devices, prevent drug degradation by limiting influx of outside biomolecules, and enhance device bioadhesion by penetrating into the mucus layer of the intestinal lining. Finally, an approach that dramatically increases the capacity and efficiency of drug loading into microdevices over previous methods is presented. A picoliter-volume printer is used to print drug directly into device reservoirs in an automated fashion. The technologies presented here expand the capabilities of microdevices for oral drug delivery by incorporating nanoscale structures that enhance device bioadhesion

  6. Oral heparin delivery: design and in vivo evaluation of a stomach-targeted mucoadhesive delivery system.

    Science.gov (United States)

    Schmitz, Thierry; Leitner, Verena M; Bernkop-Schnürch, Andreas

    2005-05-01

    Low molecular weight heparin (LMWH) is an agent of choice in the anti-coagulant therapy and prophylaxis of thrombosis and coronary syndromes. However, the therapeutic use is partially limited due to a poor oral bioavailability. It was therefore the aim of this study to design and evaluate a highly efficient stomach-targeted oral delivery system for LMWH. In order to appraise the influence of the molecular weight on the oral bioavailability, mini-tablets comprising 3 kDa (279 IU) and 6 kDa (300 IU) LMWH, respectively, were generated and tested in vivo in rats. The potential of the test formulations based on thiolated polycarbophil, was evaluated in comparison to hydroxyethylcellulose (HEC) as control carrier matrix. The plasma levels of LMWH after oral versus subcutaneous administration were determined in order to calculate the relative bioavailability. With the delivery system containing 3 kDa LMWH (279 IU) a relative bioavailability of 19.1% was achieved, offering a significantly (p thiolated polymers are a promising tool for the non-invasive stomach-targeted systemic delivery of LMWH as model for a hydrophilic macromolecular polysaccharide. Copyright 2005 Wiley-Liss, Inc

  7. Poly(amido amine) dendrimers in oral delivery.

    Science.gov (United States)

    Yellepeddi, Venkata K; Ghandehari, Hamidreza

    2016-01-01

    Poly(amidoamine) (PAMAM) dendrimers have been extensively investigated for oral delivery applications due to their ability to translocate across the gastrointestinal epithelium. In this Review, we highlight recent advances in the evaluation of PAMAM dendrimers as oral drug delivery carriers. Specifically, toxicity, mechanisms of transepithelial transport, models of the intestinal epithelial barrier including isolated human intestinal tissue model, detection of dendrimers, and surface modification are discussed. We also highlight evaluation of various PAMAM dendrimer-drug conjugates for their ability to transport across gastrointestinal epithelium for improved oral bioavailability. In addition, current challenges and future trends for clinical translation of PAMAM dendrimers as carriers for oral delivery are discussed.

  8. Oral controlled release drug delivery system and Characterization of oral tablets; A review

    OpenAIRE

    Muhammad Zaman; Junaid Qureshi; Hira Ejaz; Rai Muhammad Sarfraz; Hafeez ullah Khan; Fazal Rehman Sajid; Muhammad Shafiq ur Rehman

    2016-01-01

    Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes dif...

  9. Animal models for evaluation of oral delivery of biopharmaceuticals

    DEFF Research Database (Denmark)

    Harloff-Helleberg, Stine; Nielsen, Line Hagner; Nielsen, Hanne Mørck

    2017-01-01

    of systems for oral delivery of biopharmaceuticals may result in new treatment modalities to increase the patient compliance and reduce product cost. In the preclinical development phase, use of experimental animal models is essential for evaluation of new formulation designs. In general, the limited oral...... bioavailability of biopharmaceuticals, of just a few percent, is expected, and therefore, the animal models and the experimental settings must be chosen with utmost care. More knowledge and focus on this topic is highly needed, despite experience from the numerous studies evaluating animal models for oral drug...... delivery of small molecule drugs. This review highlights and discusses pros and cons of the most currently used animal models and settings. Additionally, it also looks into the influence of anesthetics and sampling methods for evaluation of drug delivery systems for oral delivery of biopharmaceuticals...

  10. Application of polymeric nanoparticles and micelles in insulin oral delivery

    Directory of Open Access Journals (Sweden)

    Milind Sadashiv Alai

    2015-09-01

    Full Text Available Diabetes mellitus is an endocrine disease in which the pancreas does not produce sufficient insulin or the body cannot effectively use the insulin it produces. Insulin therapy has been the best choice for the clinical management of diabetes mellitus. The current insulin therapy is via subcutaneous injection, which often fails to mimic the glucose homeostasis that occurs in normal individuals. This provokes numerous attempts to develop a safe and effective noninvasive route for insulin delivery. Oral delivery is the most convenient administration route. However, insulin cannot be well absorbed orally because of its rapid enzymatic degradation in the gastrointestinal tract. Therefore, nanoparticulate carriers such as polymeric nanoparticles and micelles are employed for the oral delivery of insulin. These nanocarriers protect insulin from degradation and facilitate insulin uptake via a transcellular and/or paracellular pathway. This review article focuses on the application of nanoparticles and micelles in insulin oral delivery. The recent advances in this topic are also reviewed.

  11. Microcontainers - an oral drug delivery system for poorly soluble drugs

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Petersen, Ritika Singh; Marizza, Paolo

    In oral delivery, it can sometimes be necessary to employ drug delivery systems to achieve targeted delivery to the intestine. Microcontainers are polymeric, cylindrical devices in the micrometer size range (Figure 1), and are suggested as a promising oral drug delivery system [1],[2]. The purpose...... of these studies was to fabricate microcontainers in either SU-8 or biodegradable poly-L-lactic acid (PLLA), and fill the microcontainers with poorly soluble drugs. Furthermore, the application of the microcontainers as an oral drug delivery system was investigated in terms of release, in situ intestinal perfusion...... medium at pH 6.5 was observed. In situ intestinal perfusions were performed in rats of the Eudragit-coated ASSF-filled microcontainers and compared to a furosemide solution. At the end of the study, the small intestine was harvested from the rat and imaged under a light microscope. The absorption rate...

  12. Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

    International Nuclear Information System (INIS)

    Nigg, David W.

    2012-01-01

    Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K(nido-7-CH3(CH2)15-7,8-C2B9H11) in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K(nido-7-CH3(CH2)15-7,8-C2B9H11) in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na3 (ae-B20H17NH3), administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 ± 16.1 ppm at 48 h and to 43.9 ± 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

  13. Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

    Energy Technology Data Exchange (ETDEWEB)

    David W. Nigg

    2012-05-01

    Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na3 [ae-B20H17NH3], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 {+-} 16.1 ppm at 48 h and to 43.9 {+-} 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

  14. Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs

    DEFF Research Database (Denmark)

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse

    2015-01-01

    Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe...... delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract...... biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral...

  15. Oral transmucosal drug delivery--current status and future prospects.

    Science.gov (United States)

    Sattar, Mohammed; Sayed, Ossama M; Lane, Majella E

    2014-08-25

    Oral transmucosal drug delivery (OTDD) dosage forms have been available since the 1980s. In contrast to the number of actives currently delivered locally to the oral cavity, the number delivered as buccal or sublingual formulations remains relatively low. This is surprising in view of the advantages associated with OTDD, compared with conventional oral drug delivery. This review examines a number of aspects related to OTDD including the anatomy of the oral cavity, models currently used to study OTDD, as well as commercially available formulations and emerging technologies. The limitations of current methodologies to study OTDD are considered as well as recent publications and new approaches which have advanced our understanding of this route of drug delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. An overview of natural polymers for oral insulin delivery.

    Science.gov (United States)

    Sonia, T A; Sharma, Chandra P

    2012-07-01

    Current therapy for diabetes mellitus through oral anti-diabetic drugs and subcutaneous administration of insulin suffers from serious disadvantages, such as patient noncompliance and occasional hypoglycemia. Moreover, these approaches doesn't mimic the normal physiological pattern of insulin release. Oral route would be the most convenient and preferred route if it is available. Polymeric nano and/or microparticles, either natural or synthetic have been used as matrices for oral insulin delivery. Natural polymers are of particular interest due to their nontoxic, biocompatible, biodegradable and hydrophilic nature. Among the natural polymers used for oral insulin delivery, chitosan (CS) is widely explored owing to its ease of chemical modification and favorable biological properties. In addition, many advantages such as safety, biodegradability, widespread availability and low cost justify the continuing development of promising insulin delivery system based on CS. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs.

    Science.gov (United States)

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse; Yang, Mingshi; Nielsen, Hanne Mørck; Mu, Huiling

    2015-01-01

    Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract are summarized. Additionally, the paper provides an overview of recent studies on characterization of solid drug carriers for peptide/protein drugs, drug distribution in particles, drug release and stability in simulated GI fluids, as well as the absorption of peptide/protein drugs in cell-based models. The use of biorelevant media when applicable can increase the knowledge about the quality of DDS for oral protein delivery. Hopefully, the knowledge provided in this review will aid the establishment of improved biorelevant models capable of forecasting the performance of particulate DDS for oral peptide/protein delivery.

  18. Oral controlled release drug delivery system and Characterization of oral tablets; A review

    Directory of Open Access Journals (Sweden)

    Muhammad Zaman

    2016-01-01

    Full Text Available Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets. 

  19. Thiomers for oral delivery of hydrophilic macromolecular drugs.

    Science.gov (United States)

    Bernkop-Schnürch, Andreas; Hoffer, Martin H; Kafedjiiski, Krum

    2004-11-01

    In recent years thiolated polymers (thiomers) have appeared as a promising new tool in oral drug delivery. Thiomers are obtained by the immobilisation of thio-bearing ligands to mucoadhesive polymeric excipients. By the formation of disulfide bonds with mucus glycoproteins, the mucoadhesive properties of thiomers are up to 130-fold improved compared with the corresponding unmodified polymers. Owing to the formation of inter- and intramolecular disulfide bonds within the thiomer itself, matrix tablets and particulate delivery systems show strong cohesive properties, resulting in comparatively higher stability, prolonged disintegration times and a more controlled drug release. The permeation of hydrophilic macromolecular drugs through the gastrointestinal (GI) mucosa can be improved by the use of thiomers. Furthermore, some thiomers exhibit improved inhibitory properties towards GI peptidases. The efficacy of thiomers in oral drug delivery has been demonstrated by various in vivo studies. A pharmacological efficacy of 1%, for example, was achieved in rats by oral administration of calcitonin tablets comprising a thiomer. Furthermore, tablets comprising a thiomer and pegylated insulin resulted in a pharmacological efficacy of 7% after oral application to diabetic mice. Low-molecular-weight heparin embedded in thiolated polycarbophil led to an absolute bioavailability of > or = 20% after oral administration to rats. In these studies, formulations comprising the corresponding unmodified polymer had only a marginal or no effect. These results indicate drug carrier systems based on thiomers appear to be a promising tool for oral delivery of hydrophilic macromolecular drugs.

  20. Potential hazards due to food additives in oral hygiene products.

    Science.gov (United States)

    Tuncer Budanur, Damla; Yas, Murat Cengizhan; Sepet, Elif

    2016-01-01

    Food additives used to preserve flavor or to enhance the taste and appearance of foods are also available in oral hygiene products. The aim of this review is to provide information concerning food additives in oral hygiene products and their adverse effects. A great many of food additives in oral hygiene products are potential allergens and they may lead to allergic reactions such as urticaria, contact dermatitis, rhinitis, and angioedema. Dental practitioners, as well as health care providers, must be aware of the possibility of allergic reactions due to food additives in oral hygiene products. Proper dosage levels, delivery vehicles, frequency, potential benefits, and adverse effects of oral health products should be explained completely to the patients. There is a necessity to raise the awareness among dental professionals on this subject and to develop a data gathering system for possible adverse reactions.

  1. POTENTIAL HAZARDS DUE TO FOOD ADDITIVES IN ORAL HYGIENE PRODUCTS

    Directory of Open Access Journals (Sweden)

    Damla TUNCER-BUDANUR

    2016-04-01

    Full Text Available Food additives used to preserve flavor or to enhance the taste and appearance of foods are also available in oral hygiene products. The aim of this review is to provide information concerning food additives in oral hygiene products and their adverse effects. A great many of food additives in oral hygiene products are potential allergens and they may lead to allergic reactions such as urticaria, contact dermatitis, rhinitis, and angioedema. Dental practitioners, as well as health care providers, must be aware of the possibility of allergic reactions due to food additives in oral hygiene products. Proper dosage levels, delivery vehicles, frequency, potential benefits, and adverse effects of oral health products should be explained completely to the patients. There is a necessity to raise the awareness among dental professionals on this subject and to develop a data gathering system for possible adverse reactions.

  2. pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms.

    Science.gov (United States)

    Liu, Lin; Yao, WenDong; Rao, YueFeng; Lu, XiaoYang; Gao, JianQing

    2017-11-01

    Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines. This review provides a wide perspective on current status of pH-responsive oral drug delivery systems prepared mainly with organic polymers or inorganic materials, including the strategies used to overcome GI barriers, the challenges in their development and future prospects, with focus on technology trends to improve the bioavailability of orally delivered drugs, the mechanisms of drug release from pH-responsive oral formulations, and their application for drug delivery, such as protein and peptide therapeutics, vaccination, inflammatory bowel disease (IBD) and bacterial infections.

  3. A review on electrospun nanofibers for oral drug delivery

    Directory of Open Access Journals (Sweden)

    Abbas Akhgari

    2017-10-01

    Full Text Available Nowadays, polymer nanofibers have gained attention due to remarkable characteristics such as high porosity and large surface area to volume ratio. Among their fabrication methods, electrospinning technique has been attracted as a simple and reproducible approach. It is a versatile, simple and cost-effective technique for the production of continuous nanofibers with acceptable characteristics such as high porosity, high surface area to volume ratio, high loading capacity and encapsulation efficiency, delivery of multiple drugs, and enhancement of drug solubility. Due to these properties electrospun nanofibers have been extensively used for different biomedical applications including wound dressing, tissue engineering, enzyme immobilization, artificial organs, and drug delivery. Different synthetic and natural polymers have been successfully electrospun into ultrafine fibers. Using electrospun nanofibers as vehicles for oral drug delivery has been investigated in different release manners- fast, biphasic or sustained release. This article presents a review on application of electrospinning technique in oral drug delivery.

  4. Polymer nanocomposite particles of S-nitrosoglutathione: A suitable formulation for protection and sustained oral delivery.

    Science.gov (United States)

    Wu, Wen; Gaucher, Caroline; Fries, Isabelle; Hu, Xian-Ming; Maincent, Philippe; Sapin-Minet, Anne

    2015-11-10

    S-nitrosoglutathione (GSNO) is a nitric oxide (NO) donor with therapeutic potential for cardiovascular disease treatment. Chronic oral treatment with GSNO is limited by high drug sensitivity to the environment and limited oral bioavailability, requiring the development of delivery systems able to sustain NO release. The present work describes new platforms based on polymer nanocomposite particles for the delivery of GSNO. Five types of optimized nanocomposite particles have been developed (three based on chitosan, two based on alginate sodium). Those nanocomposite particles encapsulate GSNO with high efficiency from 64% to 70% and an average size of 13 to 61 μm compatible with oral delivery. Sustained release of GSNO in vitro was achieved. Indeed, chitosan nanocomposites discharged their payload within 24h; whereas alginate nanocomposites released GSNO more slowly (10% of GSNO was still remaining in the dosage form after 24h). Their cytocompatibility toward intestinal Caco-2 cells (MTT assay) was acceptable (IC50: 6.07 ± 0.07-9.46 ± 0.08 mg/mL), demonstrating their suitability as oral delivery systems for GSNO. These delivery systems presented efficient GSNO loading and sustained release as well as cytocompatibility, showing their promise as a means of improving the oral bioavailability of GSNO and as a potential new treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Hydroxypropyl-β-cyclodextrin functionalized calcium carbonate microparticles as a potential carrier for enhancing oral delivery of water-insoluble drugs.

    Science.gov (United States)

    Zhang, Lihua; Zhu, Wufu; Lin, Qisi; Han, Jin; Jiang, Liqun; Zhang, Yanzhuo

    2015-01-01

    The objective of the present study was to demonstrate that a novel hydroxypropyl-β-cyclodextrin functionalized calcium carbonate (HP-β-CD/CC) based amorphous solid dispersion (ASD) can be used to increase the solubility and oral bioavailability of water-insoluble drugs. Irbesartan (IRB) was selected as a model compound and loaded into the nanoporous HP-β-CD/CC matrix using an immersion method. The IRB-loaded HP-β-CD/CC formulation was characterized by various analytical techniques, such as specific surface area analysis, scanning electron microscopy (SEM), dynamic light scattering (DLS), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Analyses with PXRD and DSC confirmed that IRB was fully converted into the amorphous form in the nanopores of HP-β-CD/CC. From the solubility and dissolution tests, it was observed that the aqueous solubility and dissolution rate of IRB-loaded HP-β-CD/CC were increased significantly compared with those of pure IRB and IRB-loaded mesoporous silica. Likewise, the IRB-loaded HP-β-CD/CC formulation exhibited better absorption compared with that of the commercially available IRB capsules in beagle dogs. The mean peak plasma concentration (C max) and the area under the mean plasma concentration-time curve (AUC[0→48]) of IRB-loaded HP-β-CD/CC were 1.56- and 1.52-fold higher than that of the commercial product, respectively. Furthermore, the IRB-loaded HP-β-CD/CC formulation exhibited excellent stability against re-crystallization. These results clearly demonstrate that HP-β-CD/CC based porous ASD is a promising formulation approach to improve the aqueous solubility and the in vivo absorption performance of a water-insoluble compound like IRB.

  6. Hydroxypropyl-β-cyclodextrin functionalized calcium carbonate microparticles as a potential carrier for enhancing oral delivery of water-insoluble drugs

    Directory of Open Access Journals (Sweden)

    Zhang L

    2015-04-01

    Full Text Available Lihua Zhang,1 Wufu Zhu,2 Qisi Lin,1 Jin Han,1 Liqun Jiang,1 Yanzhuo Zhang1,3 1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, People’s Republic of China; 2School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, Xuzhou Medical College, Xuzhou, People’s Republic of China Abstract: The objective of the present study was to demonstrate that a novel hydroxypropyl-β-cyclodextrin functionalized calcium carbonate (HP-β-CD/CC based amorphous solid dispersion (ASD can be used to increase the solubility and oral bioavailability of water-insoluble drugs. Irbesartan (IRB was selected as a model compound and loaded into the nanoporous HP-β-CD/CC matrix using an immersion method. The IRB-loaded HP-β-CD/CC formulation was characterized by various analytical techniques, such as specific surface area analysis, scanning electron microscopy (SEM, dynamic light scattering (DLS, powder X-ray diffraction (PXRD, and differential scanning calorimetry (DSC. Analyses with PXRD and DSC confirmed that IRB was fully converted into the amorphous form in the nanopores of HP-β-CD/CC. From the solubility and dissolution tests, it was observed that the aqueous solubility and dissolution rate of IRB-loaded HP-β-CD/CC were increased significantly compared with those of pure IRB and IRB-loaded mesoporous silica. Likewise, the IRB-loaded HP-β-CD/CC formulation exhibited better absorption compared with that of the commercially available IRB capsules in beagle dogs. The mean peak plasma concentration (Cmax and the area under the mean plasma concentration–time curve (AUC[0→48] of IRB-loaded HP-β-CD/CC were 1.56- and 1.52-fold higher than that of the commercial product, respectively. Furthermore, the IRB-loaded HP-β-CD/CC formulation exhibited excellent stability against re-crystallization. These results clearly

  7. Oral delivery of peptides and proteins using lipid-based drug delivery systems

    DEFF Research Database (Denmark)

    Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette

    2012-01-01

    INTRODUCTION: In order to successfully develop lipid-based drug delivery systems (DDS) for oral administration of peptides and proteins, it is important to gain an understanding of the colloid structures formed by these DDS, the mode of peptide and protein incorporation as well as the mechanism...... by which intestinal absorption of peptides and proteins is promoted. AREAS COVERED: The present paper reviews the literature on lipid-based DDS, employed for oral delivery of peptides and proteins and highlights the mechanisms by which the different lipid-based carriers are expected to overcome the two...... and proteins. EXPERT OPINION: Lipid-based DDS are safe and suitable for oral delivery of peptides and proteins. Significant progress has been made in this area with several technologies on clinical trials. However, a better understanding of the mechanism of action in vivo is needed in order to improve...

  8. Functionally engineered nanosized particles in pharmaceutics: improved oral delivery of poorly water-soluble drugs.

    Science.gov (United States)

    Ozeki, Tetsuya; Tagami, Tatsuaki

    2013-01-01

    The development of drug nanoparticles has attracted substantial attention because of their potential to improve the dissolution rate and oral availability of poorly water-soluble drugs. This review summarizes the recent articles that discussed nanoparticle-based oral drug delivery systems. The preparation methods were categorized as top-down and bottom-up methods, which are common methods for preparing drug nanoparticles. In addition, methods of handling drug nanoparticles (e.g., one-step preparation of nanocomposites which are microparticles containing drug nanoparticles) were introduced for the effective preservation of drug nanoparticles. The carrier-based preparation of drug nanoparticles was also introduced as a potentially promising oral drug delivery system.

  9. In vitro evaluation of dendrimer prodrugs for oral drug delivery.

    Science.gov (United States)

    Najlah, Mohammad; Freeman, Sally; Attwood, David; D'Emanuele, Antony

    2007-05-04

    Dendrimer-based prodrugs were used to enhance the transepithelial permeability of naproxen, a low solubility model drug. The stability of the dendrimer-naproxen link was assessed. Naproxen was conjugated to G0 polyamidoamine (PAMAM) dendrimers either by an amide bond or an ester bond. The stability of G0 prodrugs was evaluated in 80% human plasma and 50% rat liver homogenate. The cytotoxicity of conjugates towards Caco-2 cells was determined and the transport of the conjugates across Caco-2 monolayers (37 degrees C) was reported. In addition, one lauroyl chain (L) was attached to the surface group of G0 PAMAM dendrimer of the diethylene glycol ester conjugate (G0-deg-NAP) to enhance permeability. The lactic ester conjugate, G0-lact-NAP, hydrolyzed slowly in 80% human plasma and in 50% rat liver homogenate (t(1/2)=180 min). G0-deg-NAP was hydrolyzed more rapidly in 80% human plasma (t(1/2)=51 min) and was rapidly cleaved in 50% liver homogenate (t(1/2)=4.7 min). The conjugates were non-toxic when exposed to Caco-2 cells for 3h. Permeability studies showed a significant enhancement in the transport of naproxen when conjugated to dendrimers; L-G0-deg-NAP yielding the highest permeability. Dendrimer-based prodrugs with appropriate linkers have potential as carriers for the oral delivery of low solubility drugs such as naproxen.

  10. Oral delivery of peptides and proteins using lipid-based drug delivery systems.

    Science.gov (United States)

    Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette

    2012-10-01

    In order to successfully develop lipid-based drug delivery systems (DDS) for oral administration of peptides and proteins, it is important to gain an understanding of the colloid structures formed by these DDS, the mode of peptide and protein incorporation as well as the mechanism by which intestinal absorption of peptides and proteins is promoted. The present paper reviews the literature on lipid-based DDS, employed for oral delivery of peptides and proteins and highlights the mechanisms by which the different lipid-based carriers are expected to overcome the two most important barriers (extensive enzymatic degradation and poor transmucosal permeability). This paper also gives a clear-cut idea about advantages and drawbacks of using different lipidic colloidal carriers ((micro)emulsions, solid lipid core particles and liposomes) for oral delivery of peptides and proteins. Lipid-based DDS are safe and suitable for oral delivery of peptides and proteins. Significant progress has been made in this area with several technologies on clinical trials. However, a better understanding of the mechanism of action in vivo is needed in order to improve the design and development of lipid-based DDS with the desired bioavailability and therapeutic profile.

  11. Oral delivery of prolyl hydroxylase inhibitor: AKB-4924 promotes localized mucosal healing in a mouse model of colitis.

    Science.gov (United States)

    Marks, Ellen; Goggins, Bridie J; Cardona, Jocelle; Cole, Siobhan; Minahan, Kyra; Mateer, Sean; Walker, Marjorie M; Shalwitz, Robert; Keely, Simon

    2015-02-01

    Pharmacological induction of hypoxia-inducible factor (HIF), a global transcriptional regulator of the hypoxic response, by prolyl hydroxylase inhibitors (PHDi) is protective in murine models of colitis, and epithelial cells are critical for the observed therapeutic efficacy. Because systemic HIF activation may lead to potentially negative off-target effects, we hypothesized that targeting epithelial HIF through oral delivery of PHDi would be sufficient to protect against colitis in a mouse model. Using a chemically induced trinitrobenzene sulfonic acid murine model of colitis, we compared the efficacy of oral and intraperitoneal (i.p.) delivery of the PHDi; AKB-4924 in preventing colitis, as measured by endoscopy, histology, barrier integrity, and immune profiling. Furthermore, we measured potential off-target effects, examining HIF and HIF target genes in the heart and kidney, as well as erythropoietin and hematocrit levels. Oral administration of AKB-4924 exhibited mucosal protection comparable i.p. dosing. Oral delivery of PHDi led to reduced colonic epithelial HIF stabilization compared with i.p. delivery, but this was still sufficient to induce transcription of downstream HIF targets. Furthermore, oral delivery of PHDi led to reduced stabilization of HIF and activation of HIF targets in extraintestinal organs. Oral delivery of PHDi therapies to this intestinal mucosa protects against colitis in animal models and represents a potential therapeutic strategy for inflammatory bowel disease, which also precludes unwanted extraintestinal effects.

  12. Oral Delivery of Protein Drugs Bioencapsulated in Plant Cells.

    Science.gov (United States)

    Kwon, Kwang-Chul; Daniell, Henry

    2016-08-01

    Plants cells are now approved by the FDA for cost-effective production of protein drugs (PDs) in large-scale current Good Manufacturing Practice (cGMP) hydroponic growth facilities. In lyophilized plant cells, PDs are stable at ambient temperature for several years, maintaining their folding and efficacy. Upon oral delivery, PDs bioencapsulated in plant cells are protected in the stomach from acids and enzymes but are subsequently released into the gut lumen by microbes that digest the plant cell wall. The large mucosal area of the human intestine offers an ideal system for oral drug delivery. When tags (receptor-binding proteins or cell-penetrating peptides) are fused to PDs, they efficiently cross the intestinal epithelium and are delivered to the circulatory or immune system. Unique tags to deliver PDs to human immune or nonimmune cells have been developed recently. After crossing the epithelium, ubiquitous proteases cleave off tags at engineered sites. PDs are also delivered to the brain or retina by crossing the blood-brain or retinal barriers. This review highlights recent advances in PD delivery to treat Alzheimer's disease, diabetes, hypertension, Gaucher's or ocular diseases, as well as the development of affordable drugs by eliminating prohibitively expensive purification, cold chain and sterile delivery.

  13. Critical gases for critical issues: CO2 technologies for oral drug delivery.

    Science.gov (United States)

    Danan, Hana; Esposito, Pierandrea

    2014-02-01

    In recent years, CO2-based technologies have gained considerable interest in the pharmaceutical industry for their potential applications in drug formulation and drug delivery. The exploitation of peculiar properties of gases under supercritical conditions has been studied in the last 20 years with mixed results. Promising drug-delivery technologies, based on supercritical CO2, have mostly failed when facing challenges of industrial scaleability and economical viability. Nevertheless, a 'second generation' of processes, based on CO2 around and below critical point has been developed, possibly offering technology-based solutions to some of the current issues of pharmaceutical development. In this review, we highlight the most recent advancements in this field, with a particular focus on the potential of CO2-based technologies in addressing critical issues in oral delivery, and briefly discuss the future perspectives of dense CO2-assisted processes as enabling technologies in drug delivery.

  14. Thiolated nanocarriers for oral delivery of hydrophilic macromolecular drugs.

    Science.gov (United States)

    Dünnhaupt, S; Barthelmes, J; Köllner, S; Sakloetsakun, D; Shahnaz, G; Düregger, A; Bernkop-Schnürch, A

    2015-03-06

    It was the aim of this study to investigate the effect of unmodified as well as thiolated anionic poly(acrylic acid) (PAA) and cationic chitosan (CS) utilized in free-soluble form and as nanoparticulate system on the absorption of the hydrophilic compound FD4 across intestinal epithelial cell layer with and without a mucus layer. Modifications of these polymers were achieved by conjugation with cysteine to PAA (PAA-Cys) and thioglycolic acid to CS (CS-TGA). Particles were prepared via ionic gelation and characterized based on their amount of thiol groups, particle size and zeta potential. Effects on the cell layer concerning absorption enhancement, transepithelial electrical resistance (TEER) and cytotoxicity were investigated. Permeation enhancement was evaluated with respect to in vitro transport of FD4 across Caco-2 cells, while mucoadhesion was indirectly examined in terms of adsorption behaviour when cells were covered with a mucus layer. Lyophilized particles displayed around 1000 μmol/g of free thiol groups, particle sizes of less than 300 nm and a zeta potential of 18 mV (CS-TGA) and -14 mV (PAA-Cys). Cytotoxicity studies confirmed that all polymer samples were used at nontoxic concentrations (0.5% m/v). Permeation studies revealed that all thiolated formulations had pronounced effects on the paracellular permeability of mucus-free Caco-2 layers and enhanced the permeation of FD4 3.0- to 5.3-fold. Moreover, polymers administered as particles showed a higher permeation enhancement than their corresponding solutions. However, the absorption-enhancing effect of each thiolated formulation was significantly (pthiolated polymers as nanoparticulate delivery systems represent a promising tool for the oral administration of hydrophilic macromolecules. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. In-vitro analysis of APA microcapsules for oral delivery of live bacterial cells.

    Science.gov (United States)

    Chen, H; Ouyang, W; Jones, M; Haque, T; Lawuyi, B; Prakash, S

    2005-08-01

    Oral administration of microcapsules containing live bacterial cells has potential as an alternative therapy for several diseases. This article evaluates the suitability of the alginate-poly-L-lysine-alginate (APA) microcapsules for oral delivery of live bacterial cells, in-vitro, using a dynamic simulated human gastro-intestinal (GI) model. Results showed that the APA microcapsules were morphologically stable in the simulated stomach conditions, but did not retain their structural integrity after a 3-day exposure in simulated human GI media. The microbial populations of the tested bacterial cells and the activities of the tested enzymes in the simulated human GI suspension were not substantially altered by the presence of the APA microcapsules, suggesting that there were no significant adverse effects of oral administration of the APA microcapsules on the flora of the human gastrointestinal tract. When the APA microcapsules containing Lactobacillus plantarum 80 (LP80) were challenged in the simulated gastric medium (pH = 2.0), 80.0% of the encapsulated cells remained viable after a 5-min incubation; however, the viability decreased considerably (8.3%) after 15 min and dropped to 2.6% after 30 min and lower than 0.2% after 60 min, indicating the limitations of the currently obtainable APA membrane for oral delivery of live bacteria. Further in-vivo studies are required before conclusions can be made concerning the inadequacy of APA microcapsules for oral delivery of live bacterial cells.

  16. Advanced progress of microencapsulation technologies: in vivo and in vitro models for studying oral and transdermal drug deliveries.

    Science.gov (United States)

    Lam, P L; Gambari, R

    2014-03-28

    This review provides an overall discussion of microencapsulation systems for both oral and transdermal drug deliveries. Clinically, many drugs, especially proteins and peptides, are susceptible to the gastrointestinal tract and the first-pass metabolism after oral administration while some drugs exhibit low skin permeability through transdermal delivery route. Medicated microcapsules as oral and transdermal drug delivery vehicles are believed to offer an extended drug effect at a relatively low dose and provide a better patient compliance. The polymeric microcapsules can be produced by different microencapsulation methods and the drug microencapsulation technology provides the quality preservation for drug stabilization. The release of the entrapped drug is controlled and prolonged for specific usages. Some recent studies have focused on the evaluation of drug containing microcapsules on potential biological and therapeutic applications. For the oral delivery, in vivo animal models were used for evaluating possible treatment effects of drug containing microcapsules. For the transdermal drug delivery, skin delivery models were introduced to investigate the potential skin delivery of medicated microcapsules. Finally, the challenges and limitations of drug microencapsulation in real life are discussed and the commercially available drug formulations using microencapsulation technology for oral and transdermal applications are shown. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Delivery of bioactive peptides and proteins across oral (buccal) mucosa.

    Science.gov (United States)

    Senel, S; Kremer, M; Nagy, K; Squier, C

    2001-06-01

    The identification of an increasing array of highly potent, endogenous peptide and protein factors termed cytokines, that can be efficiently synthesized using recombinant DNA technology, offers exciting new approaches for drug therapy. However, the physico-chemical and biological properties of these agents impose limitations in formulation and development of optimum drug delivery systems as well as on the routes of delivery. Oral mucosa, including the lining of the cheek (buccal mucosa), floor of mouth and underside of tongue (sublingual mucosa) and gingival mucosa, has received much attention in the last decade because it offers excellent accessibility, is not easily traumatized and avoids degradation of proteins and peptides that occurs as a result of oral administration, gastrointestinal absorption and first-pass hepatic metabolism. Peptide absorption occurs across oral mucosa by passive diffusion and it is unlikely that there is a carrier-mediated transport mechanism. The principal pathway is probably via the intercellular route where the major permeability barrier is represented by organized array of neutral lipids in the superficial layers of the epithelium. The relative role of aqueous as opposed to the lipid pathway in drug transport is still under investigation; penetration is not necessarily enhanced by simply increasing lipophilicity, for other effects, such as charge and molecular size, also play an important role in absorption of peptide and protein drugs. Depending on the pharmacodynamics of the peptides, various oral mucosal delivery systems can be designed. Delivery of peptide/protein drugs by conventional means such as solutions has some limitations. The possibility of excluding a major part of drug from absorption by involuntary swallowing and the continuous dilution due to salivary flow limits a controlled release. However these limitations can be overcome by adhesive dosage forms such as gels, films, tablets, and patches. They can localize the

  18. Physiological barriers to the oral delivery of curcumin.

    Science.gov (United States)

    Berginc, K; Trontelj, J; Basnet, N Skalko; Kristl, A

    2012-06-01

    Curcumin, a principal component from Curcuma longa, with antioxidant and anti-inflammatory activities was proposed as a potential candidate for the preventation and/or treatment of cancer and chronic diseases. However, curcumin could not achieve its expected therapeutic outcome in clinical trials due to its low solubility and poor bioavailability. The actual intestinal physiological barriers limiting curcumin absorption after oral administration have not been fully investigated. To identify the main barriers curtailing its absorption, in vitro permeability of curcumin and flux of its glucuronide were monitored in rat jejunum and Transwell grown Caco-2 cells. Curcumin was more permeable under acidic conditions, but the permeability was substantially below the permeability of highly permeable standards. Its efflux could not be inhibited by specific Pgp and MRP inhibitors. BCRP was found to participate in curcumin transport, but the Organic Anion Transporting Polypeptide (OATP) did not. The permeability of curcumin significantly increased when the structure of mucus was compromised. The inhibitor of curcumin metabolism, piperin, failed to act as a permeability enhancer. Piperin inhibited Pgp and MRP transporters and decreased the amount of glucuronide transported back into the intestine. Inclusion of piperin in curcumin-containing formulations is highly recommended as to inhibit curcumin glucuronidation and to increase the transport of formed glucuronides into the plasma, therefore increasing the probability of glucuronide distribution into target tissue and inter-convertion to curcumin. It would also be beneficial, if curcumin delivery systems could reversibly compromise the mucous integrity to minimize the non-specific binding of curcumin to its constituents.

  19. Cell-Penetrating Peptides as Carriers for Oral Delivery of Biopharmaceuticals

    DEFF Research Database (Denmark)

    Kristensen, Mie; Nielsen, Hanne Mørck

    2016-01-01

    Oral delivery of biopharmaceuticals, for example peptides and proteins, constitutes a great challenge in drug delivery due to their low chemical stability and poor permeation across the intestinal mucosa, to a large extent limiting the mode of administration to injections, which is not favouring...... patient compliance. Nevertheless, cell-penetrating peptides (CPPs) have shown promising potential as carriers to overcome the epithelium, and this minireview highlights recent knowledge gained within the field of CPP-mediated transepithelial delivery of therapeutic peptides and proteins from the intestine...... is to be preferred depends on the physicochemical properties of both the specific CPP and the specific cargo. In addition to the physical epithelial barrier, a metabolic barrier must be overcome in order to obtain CPP-mediated delivery of a cargo drug from the intestine, and a number of strategies have been employed...

  20. 3D printing of a wearable personalized oral delivery device: A first-in-human study

    Science.gov (United States)

    Brambilla, Davide

    2018-01-01

    Despite the burgeoning interest in three-dimensional (3D) printing for the manufacture of customizable oral dosage formulations, a U.S. Food and Drug Administration–approved tablet notwithstanding, the full potential of 3D printing in pharmaceutical sciences has not been realized. In particular, 3D-printed drug-eluting devices offer the possibility for personalization in terms of shape, size, and architecture, but their clinical applications have remained relatively unexplored. We used 3D printing to manufacture a tailored oral drug delivery device with customizable design and tunable release rates in the form of a mouthguard and, subsequently, evaluated the performance of this system in the native setting in a first-in-human study. Our proof-of-concept work demonstrates the immense potential of 3D printing as a platform for the development and translation of next-generation drug delivery devices for personalized therapy. PMID:29750201

  1. Mucoadhesive oral films: The potential for unmet needs.

    Science.gov (United States)

    Silva, Branca M A; Borges, Ana Filipa; Silva, Cláudia; Coelho, Jorge F J; Simões, Sérgio

    2015-10-15

    Oral drug delivery is the most common route of drug administration. Nevertheless, there are some important limitations that reinforce the need for developing new drug delivery systems. Mucoadhesive oral films (MOF) are promising dosage forms that adhere to the oral mucosa and deliver the drug through it, which present several advantages. These include: bypassing the hepatic first pass effect, fast onset of action, ease of transportation and handling. The use of such dosage form is beneficial for drugs that have poor oral bioavailability and also for drugs that need to be rapidly absorbed. In spite of the known benefits, the number of marketed MOF is still quite small. This review explores the products under development and corresponding clinical trials in respect to their status, therapeutic indication, companies involved and technologies. In this way, it was possible to identify the preferred therapeutic indications, new research and market trends as well as future prospects of MOF. Moreover, it is reasonable to expect an increase in the number of products on the market due to their great potential to satisfy unmet medical needs. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Fabrication and loading of microcontainers for oral drug delivery

    DEFF Research Database (Denmark)

    Petersen, Ritika Singh

    is an important loop diuretic drug with low solubility and permeability is used as a model drug and embedded in a PCL matrix. The crystallinity of the drug is tailored by the process parameters of spin coating. Release profiles ranging from rapid burst release to sustained zero-order release are obtained......Oral drug delivery is considered as the most patient compliant delivery route. However, it faces many obstacles, especially due to the ever-increasing number of drugs that are poorly soluble and barely absorbed in the gastro-intestinal tract. Moreover, drugs can degrade in the harsh acidic...... in this project. This process utilizes a stamp in connection with the ability to apply heat and pressure to transfer the stamp pattern to a film. Processes have been optimized for fabrication of nickel stamps with two layered, high aspect ratio microstructures. Bosch deep reactive ion etching of Silicon producing...

  3. Novel PLGA-based nanoparticles for the oral delivery of insulin

    Directory of Open Access Journals (Sweden)

    Malathi S

    2015-03-01

    Full Text Available Sampath Malathi,1 Perumal Nandhakumar,2 Velayudham Pandiyan,2 Thomas J Webster,3 Sengottuvelan Balasubramanian1 1Department of Inorganic Chemistry, Guindy Campus, University of Madras, Chennai, Tamil Nadu, India; 2Department of Veterinary Biochemistry, Madras Veterinary College, Chennai, Tamil Nadu, India; 3Department of Chemical Engineering, Northeastern University, Boston, USA Background: Insulin is the drug therapy for patients with insulin-dependent diabetes mellitus. A number of attempts have been made in the past to overcome the problems associated with the oral delivery of insulin, but with little success. Orally administered insulin has encountered with many difficulties such as rapid degradation and poor intestinal absorption. The potential use of d-α-tocopherol poly(ethylene glycol 1000 succinate (TPGS-emulsified poly(ethylene glycol (PEG-capped poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs was investigated for sustained delivery of insulin (IS.Objective: To investigate the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs as a potential drug carrier for the oral delivery of insulin.Methods: A series of biodegradable low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6] copolymers were synthesized by melt polycondensation. The commercial insulin-loaded TPGS-emulsified PEG-capped PLGA NPs (ISTPPLG NPs were synthesized by water–oil–water emulsion solvent evaporation method. The physical and chemical properties of PLGA copolymers, particle size, zeta potential, and morphology of the NPs were examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by oral administration.Results: The maximum encapsulation efficiency of ISTPPLG6 NPs was 78.6%±1.2%, and the mean diameter of the NPs was 180±20 nm. The serum glucose level was significantly (twofold decreased on treatment with ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30 NPs when compared to that of free

  4. Orally-dissolving film for sublingual and buccal delivery of ropinirole.

    Science.gov (United States)

    Lai, Ka Lun; Fang, Yuan; Han, Hao; Li, Qingqing; Zhang, Shuai; Li, Ho Yin; Chow, Shing Fung; Lam, Tai Ning; Lee, Wai Yip Thomas

    2018-03-01

    Ropinirole is a very important treatment option for Parkinson's disease (PD), a major threat to the aging population. However, this drug undergoes extensive first-pass metabolism, resulting in a low oral bioavailability. Moreover, the necessity of frequent administration due to the short half-life of ropinirole may jeopardize patient compliance. Indeed, taking this drug in solid oral dosage forms (e.g. Tablet) can be a challenge because of the tremor, rigidity, limited mobility, and impaired drug absorption experienced by PD patients. In light of these, there is a pressing need to devise formulations for the delivery of ropinirole that allow simple and easy administration and fast drug action, as well as avoidance of first-pass metabolism and overcoming the challenge of impaired absorption due to gastrointestinal dysfunctions, etc. Herein, we seek to overcome all these challenges via sublingual or buccal delivery of orally-dissolving films. Accordingly, we aimed to fabricate and characterize orally-dissolving films of ropinirole and assess their in vivo pharmacokinetics after sublingual and buccal administration. The ropinirole oral film was non-toxic and exhibited fast disintegration and dissolution and was physically stable for at least 28 days. Upon buccal/sublingual administration of the oral films, ropinirole reached the systemic circulation within 15 min and bioavailability was significantly improved, which may be attributable to avoidance of first-pass metabolism via absorption through the oral cavity. In conclusion, our ropinirole oral film improved bioavailability after sublingual or buccal administration. This formulation potentially overcomes biopharmaceutical challenges and provide a convenient means of administration of ropinirole or other anti-PD drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Oral Health Care Delivery Within the Accountable Care Organization.

    Science.gov (United States)

    Blue, Christine; Riggs, Sheila

    2016-06-01

    The accountable care organization (ACO) provides an opportunity to strategically design a comprehensive health system in which oral health works within primary care. A dental hygienist/therapist within the ACO represents value-based health care in action. Inspired by health care reform efforts in Minnesota, a vision of an accountable care organization that integrates oral health into primary health care was developed. Dental hygienists and dental therapists can help accelerate the integration of oral health into primary care, particularly in light of the compelling evidence confirming the cost-effectiveness of care delivered by an allied workforce. A dental insurance Chief Operating Officer and a dental hygiene educator used their unique perspectives and experience to describe the potential of an interdisciplinary team-based approach to individual and population health, including oral health, via an accountable care community. The principles of the patient-centered medical home and the vision for accountable care communities present a paradigm shift from a curative system of care to a prevention-based system that encompasses the behavioral, social, nutritional, economic, and environmental factors that impact health and well-being. Oral health measures embedded in the spectrum of general health care have the potential to ensure a truly comprehensive healthcare system. Published by Elsevier Inc.

  6. Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen

    DEFF Research Database (Denmark)

    Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    PURPOSE: The present work reports rationalized development and characterization of solidified self-nanoemulsifying drug delivery system for oral delivery of combinatorial (tamoxifen and quercetin) therapeutic regimen. METHODS: Suitable oil for the preparation of liquid SNEDDS was selected based...

  7. Physiological parameters for oral delivery and in vitro testing.

    Science.gov (United States)

    Mudie, Deanna M; Amidon, Gordon L; Amidon, Gregory E

    2010-10-04

    Pharmaceutical solid oral dosage forms must undergo dissolution in the intestinal fluids of the gastrointestinal tract before they can be absorbed and reach the systemic circulation. Therefore, dissolution is a critical part of the drug-delivery process. The rate and extent of drug dissolution and absorption depend on the characteristics of the active ingredient as well as properties of the dosage form. Just as importantly, characteristics of the physiological environment such as buffer species, pH, bile salts, gastric emptying rate, intestinal motility, and hydrodynamics can significantly impact dissolution and absorption. While significant progress has been made since 1970 when the first compendial dissolution test was introduced (USP apparatus 1), current dissolution testing does not take full advantage of the extensive physiologic information that is available. For quality control purposes, where the question is one of lot-to-lot consistency in performance, using nonphysiologic test conditions that match drug and dosage form properties with practical dissolution media and apparatus may be appropriate. However, where in vitro-in vivo correlations are desired, it is logical to consider and utilize knowledge of the in vivo condition. This publication critically reviews the literature that is relevant to oral human drug delivery. Physiologically relevant information must serve as a basis for the design of dissolution test methods and systems that are more representative of the human condition. As in vitro methods advance in their physiological relevance, better in vitro-in vivo correlations will be possible. This will, in turn, lead to in vitro systems that can be utilized to more effectively design dosage forms that have improved and more consistent oral bioperformance.

  8. Biodegradable microcontainers as an oral drug delivery system for poorly soluble drugs

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Nagstrup, Johan; Keller, Stephan Sylvest

    2013-01-01

    PURPOSE: To fabricate microcontainers in biodegradable polylactic acid (PLLA) polymer films using hot embossing, and investigate the application of fabricated microcontainers as an oral drug delivery system for a poorly soluble drug. METHODS: For fabrication of the PLLA microcontainers, a film...... (produced by spray drying) using a simplified version of a screen printing technique. An enteric-resistant lid of Eudragit L-100 was subsequently spray coated onto the cavity of the microcontainers. Release of amorphous furosemide salt from the coated microcontainers was investigated using a μ-Diss profiler...... release from microcontainers in gastric medium, and facilitated an immediate release in the intestinal medium. The fabricated microcontainers therefore show considerable future potential as oral drug delivery systems....

  9. Microcontainers as an oral delivery system for spray dried cubosomes containing ovalbumin

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Rades, Thomas; Boyd, Ben

    2017-01-01

    The purpose of this study was to prepare cubosomes encapsulating the model antigen ovalbumin (OVA) via spray drying, and to characterise such cubosomes with a view for their potential application in oral vaccine delivery. Furthermore the cubosome formulation was loaded into polymeric...... microcontainers intended as an oral drug delivery system. The cubosomes consisted of commercial glyceryl monooleate, Dimodan®, containing OVA and were surrounded with a dextran shell prepared by spray drying. Cryo-TEM was used to confirm that cubosomes were formed after hydration of the spray dried precursor...... the cubosomes and microcontainers occurred at pH 6.8, releasing 44.1±5.6% of the OVA in 96h. Small-angle X-ray scattering (SAXS) revealed that the 'dry' particles possessed an internal ordered lipid structure (lamellar and inverse micellar phase) by virtue of a small amount of residual water, and after...

  10. Drug delivery from the oral cavity: a focus on mucoadhesive buccal drug delivery systems.

    Science.gov (United States)

    Shinkar, Dattatraya Manohar; Dhake, Avinash Sridhar; Setty, Chitral Mallikarjuna

    2012-01-01

    Since the early 1980s the concept of mucoadhesion has gained considerable interest in pharmaceutical technology. The various advantages associated with these systems made buccal drug delivery as a novel route of drug administration. It prolongs the residence time of the dosage form at the site of application. These systems remain in close contact with the absorption tissue, the mucous membrane, and thus contribute to improved and/or better therapeutic performance of the drug and of both local and systemic effects. This review highlights the anatomy and structure of oral mucosa, mechanism and theories of mucoadhesion, factors affecting mucoadhesion, characteristics and properties of desired mucoadhesive polymers, various types of dosage forms, and general considerations in design of mucoadhesive buccal dosage forms, permeation enhancers, and evaluation methods. Over the past few decades the mucoadhesive buccal drug delivery system has received a great deal of attention to develop mucoadhesive dosage forms to enable the prolonged retention at the site of action, providing a controlled release of drug for improved therapeutic outcome. Mucoadhesive drug delivery gives facility to include a permeation enhancer/enzyme inhibitor or pHmodifier in the formulation and versatility in designing as multidirectional or unidirectional release systems for local and systemic action. Local delivery to tissues of the oral cavity has a number of applications, including treatment of local conditions such as periodontal disease, bacterial and fungal infections, and aphthous stomatitis and vesiculo bullous diseases. For the treatment of chronic diseases, the mucoadhesive buccal drug delivery system allows easily accessibility and is generally well-accepted for administeringdrugs by systemic action.

  11. Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid-State Lipid-Based Drug Delivery Systems.

    Science.gov (United States)

    Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

    2016-01-01

    Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs. Despite the successful commercialization of several LBDDS products over the years, a large discrepancy exists between the number of poorly water-soluble drugs displaying suboptimal in vivo performances and the application of LBDDS to mitigate their various delivery challenges. Conventional LBDDS, including lipid solutions and suspensions, emulsions, and self-emulsifying formulations, suffer from various drawbacks limiting their widespread use and commercialization. Accordingly, solid-state LBDDS, fabricated by adsorbing LBDDS onto a chemically inert solid carrier material, have attracted substantial interest as a viable means of stabilizing LBDDS whilst eliminating some of the various limitations. This review describes the impact of solid carrier choice on LBDDS performance and highlights the importance of appropriate solid carrier material selection when designing hybrid solid-state LBDDS. Specifically, emphasis is placed on discussing the ability of the specific solid carrier to modulate drug release, control lipase action and lipid digestion, and enhance biopharmaceutical performance above the original liquid-state LBDDS. To encourage the interested reader to consider their solid carrier choice on a higher level, various novel materials with the potential for future use as solid carriers for LBDDS are described. This review is highly significant in guiding future research directions in the solid-state LBDDS field and fostering the translation of these delivery systems to the pharmaceutical marketplace.

  12. Nanotechnology in dentistry: drug delivery systems for the control of biofilm-dependent oral diseases.

    Science.gov (United States)

    de Sousa, Francisco Fabio Oliveira; Ferraz, Camila; Rodrigues, Lidiany K Arla de Azevedo; Nojosa, Jacqueline de Santiago; Yamauti, Monica

    2014-01-01

    Dental disorders, such as caries, periodontal and endodontic diseases are major public health issues worldwide. In common, they are biofilm-dependent oral diseases, and the specific conditions of oral cavity may develop infectious foci that could affect other physiological systems. Efforts have been made to develop new treatment routes for the treatment of oral diseases, and therefore, for the prevention of some systemic illnesses. New drugs and materials have been challenged to prevent and treat these conditions, especially by means of bacteria elimination. "Recent progresses in understanding the etiology, epidemiology and microbiology of the microbial flora in those circumstances have given insight and motivated the innovation on new therapeutic approaches for the management of the oral diseases progression". Some of the greatest advances in the medical field have been based in nanosized systems, ranging from the drug release with designed nanoparticles to tissue scaffolds based on nanotechnology. These systems offer new possibilities for specific and efficient therapies, been assayed successfully in preventive/curative therapies to the oral cavity, opening new challenges and opportunities to overcome common diseases based on bacterial biofilm development. The aim of this review is to summarize the recent nanotechnological developments in the drug delivery field related to the prevention and treatment of the major biofilm-dependent oral diseases and to identify those systems, which may have higher potential for clinical use.

  13. Probiotic Ferulic Acid Esterase Active Lactobacillus fermentum NCIMB 5221 APA Microcapsules for Oral Delivery: Preparation and in Vitro Characterization

    OpenAIRE

    Tomaro-Duchesneau, Catherine; Saha, Shyamali; Malhotra, Meenakshi; Coussa-Charley, Michael; Kahouli, Imen; Jones, Mitchell L.; Labb?, Alain; Prakash, Satya

    2012-01-01

    Probiotics possess potential therapeutic and preventative effects for various diseases and metabolic disorders. One important limitation for the oral delivery of probiotics is the harsh conditions of the upper gastrointestinal tract (GIT) which challenge bacterial viability and activity. One proposed method to surpass this obstacle is the use of microencapsulation to improve the delivery of bacterial cells to the lower GIT. The aim of this study is to use alginate-poly-L-lysine-alginate (APA)...

  14. Self-assembling bubble carriers for oral protein delivery.

    Science.gov (United States)

    Chuang, Er-Yuan; Lin, Kun-Ju; Lin, Po-Yen; Chen, Hsin-Lung; Wey, Shiaw-Pyng; Mi, Fwu-Long; Hsiao, Hsu-Chan; Chen, Chiung-Tong; Sung, Hsing-Wen

    2015-09-01

    Successful oral delivery of therapeutic proteins such as insulin can greatly improve the quality of life of patients. This study develops a bubble carrier system by loading diethylene triamine pentaacetic acid (DTPA) dianhydride, a foaming agent (sodium bicarbonate; SBC), a surfactant (sodium dodecyl sulfate; SDS), and a protein drug (insulin) in an enteric-coated gelatin capsule. Following oral administration to diabetic rats, the intestinal fluid that has passed through the gelatin capsule saturates the mixture; concomitantly, DTPA dianhydride produces an acidic environment, while SBC decomposes to form CO2 bubbles at acidic pH. The gas bubbles grow among the surfactant molecules (SDS) owing to the expansion of the generated CO2. The walls of the CO2 bubbles consist of a self-assembled film of water that is in nanoscale and may serve as a colloidal carrier to transport insulin and DTPA. The grown gas bubbles continue to expand until they bump into the wall and burst, releasing their transported insulin, DTPA, and SDS into the mucosal layer. The released DTPA and SDS function as protease inhibitors to protect the insulin molecules as well as absorption enhancers to augment their epithelial permeability and eventual absorption into systemic circulation, exerting their hypoglycemic effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals.

    Science.gov (United States)

    Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

    2017-01-01

    Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations.

  16. The Oral Health Care Delivery System in 2040: Executive Summary.

    Science.gov (United States)

    Bailit, Howard L

    2017-09-01

    This executive summary for Section 4 of the "Advancing Dental Education in the 21 st Century" project examines the projected oral health care delivery system in 2040 and the likely impact of system changes on dental education. Dental care is at an early stage of major changes with the decline in solo practice and increase in large group practices. These groups are not consolidated at the state level, but further consolidation is expected as they try to increase their negotiating leverage with dental insurers. At this time, there is limited integration of medical and dental care in terms of financing, regulation, education, and delivery. This pattern may change as health maintenance organizations and integrated medical systems begin to offer dental care to their members. By 2040, it is expected that many dentists will be employed in large group practices and working with allied dental staff with expanded duties and other health professionals, and more dental graduates will seek formal postdoctoral training to obtain better positions in group practices.

  17. Oral delivery of capsaicin using MPEG-PCL nanoparticles.

    Science.gov (United States)

    Peng, Wei; Jiang, Xin-yi; Zhu, Yuan; Omari-Siaw, E; Deng, Wen-wen; Yu, Jiang-nan; Xu, Xi-ming; Zhang, Wei-ming

    2015-01-01

    To prepare a biodegradable polymeric carrier for oral delivery of a water-insoluble drug capsaicin (CAP) and evaluate its quality. CAP-loaded methoxy poly (ethylene glycol)-poly(ε-caprolactone) nanoparticles (CAP/NPs) were prepared using a modified emulsification solvent diffusion technique. The quality of CAP/NPs were evaluated using transmission electron microscopy, powder X-ray diffraction, differential scanning calorimetry and Fourier transform infrared techniques. A dialysis method was used to analyze the in vitro release profile of CAP from the CAP/NPs. Adult male rats were orally administered CAP/NPs (35 mg/kg), and the plasma concentrations of CAP were measured with a validated HPLC method. The morphology of rat gastric mucosa was studied with HE staining. CAP/NPs had an average diameter of 82.54 ± 0.51 nm, high drug-loading capacity of 14.0% ± 0.13% and high stability. CAP/NPs showed a biphasic release profile in vitro: the burst release was less than 25% of the loaded drug within 12 h followed by a more sustained release for 60 h. The pharmacokinetics study showed that the mean maximum plasma concentration was observed 4 h after oral administered of CAP/NPs, and approximately 90 ng/mL of CAP was detected in serum after 36 h. The area under the curve for the CAP/NPs group was approximately 6-fold higher than that for raw CAP suspension. Histological studies showed that CAP/NPs markedly reduced CAP-caused gastric mucosa irritation. CAP/NPs significantly enhance the bioavailability of CAP and markedly reduce gastric mucosa irritation in rats.

  18. 76 FR 25696 - Guidance for Industry on Dosage Delivery Devices for Orally Ingested OTC Liquid Drug Products...

    Science.gov (United States)

    2011-05-05

    ... are manufacturing, marketing, or distributing orally ingested over-the-counter (OTC) liquid drug... overdoses that can result from the use of dosage delivery devices with markings that are inconsistent or... because of ongoing concerns about potentially serious accidental drug overdoses that can result from the...

  19. Application of in situ polymerization for design and development of oral drug delivery systems.

    Science.gov (United States)

    Ngwuluka, Ndidi

    2010-12-01

    Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides to overcome the challenges of oral route of administration.

  20. Application of In Situ Polymerization for Design and Development of Oral Drug Delivery Systems

    OpenAIRE

    Ngwuluka, Ndidi

    2010-01-01

    Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides to overcome the challenges of oral route of administration.

  1. Identifying Potential Child Abuse through Oral Examination

    Directory of Open Access Journals (Sweden)

    Jillian N. Printz

    2017-01-01

    Full Text Available Limited reports of oropharyngeal trauma exist in the literature even though this type of injury is extremely common in pediatric populations. There are no widely agreed upon diagnostic and management tools for such injuries in abuse cases, emphasizing the importance of reporting rare cases of orofacial trauma. This case report of a soft palate laceration demonstrates an instance of initially unrecognized potential child abuse. We aim to clarify understanding of such injuries. Furthermore, the report highlights the need for recognition of oral signs of child abuse in order to promote early detection, reporting, and appropriate management.

  2. Cytotoxicity and Acute Gastrointestinal Toxicity of Bacterial Cellulose-Poly (acrylamide-sodium acrylate Hydrogel: A Carrier for Oral Drug Delivery

    Directory of Open Access Journals (Sweden)

    Manisha Pandey 1,2 * , Hira Choudhury 1, Mohd Cairul Iqbal Mohd Amin 2

    2016-12-01

    Full Text Available Background: Preliminary safety evaluation of polymer intended to use as drug delivery carrier is essential. Methods: In this study polyacrylamide grafted bacterial cellulose (BC/AM hydrogel was prepared by microwave irradiation initiated free radical polymerization. The synthesized hydrogel was subjected to in vitro cytotoxicity and acute gastrointestinal toxicity studies to evaluate its biological safety as potential oral drug delivery carrier. Results: The results indicate that hydrogel was non cytotoxic and did not show any histopathological changes in GI tract after a high dose of oral administration. Conclusion: The results revealed that hydrogel composed of bacterial cellulose and polyacrylamide is safe as oral drug delivery carrier.

  3. Encapsulation of Liposomes within pH Responsive Microspheres for Oral Colonic Drug Delivery

    Directory of Open Access Journals (Sweden)

    M. J. Barea

    2012-01-01

    Full Text Available A novel liposome-in-microsphere (LIM formulation has been created comprising drug-loaded liposomes within pH responsive Eudragit S100 microspheres. The liposomes contained the model drug 5-ASA and were coated with chitosan in order to protect them during encapsulation within the microspheres and to improve site-specific release characteristics. In vitro drug release studies showed that LIMs prevented drug release within simulated stomach and small intestine conditions with subsequent drug release occurring in large intestine conditions. The formulation therefore has potential for oral colonic drug delivery.

  4. Soft-Template-Synthesized Mesoporous Carbon for Oral Drug Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Saha, Dipendu [ORNL; Warren, Kaitlyn E [ORNL; Naskar, Amit K [ORNL

    2014-01-01

    Template-synthesized mesoporous carbons were successfully used in in vitro investigations of controlled delivery of three model drugs, captopril, furosemide, and ranitidine hydrochloride. Captopril and furosemide exhibited desorption kinetics over 30 40 h, and ranitidine HCl had a complete release time of 5 10 h. As evident from the slow release kinetics, we contend that our mesoporous carbon is an improved drug-delivery medium compared to state-of-the-art porous silica-based substrates. The mesoporous carbons, synthesized from phloroglucinol and lignin, a synthetic and a sustainable precursor, respectively, exhibit BET surface area of 200 400 m2 g-1 and pore volume of 0.2 0.6 cm3 g-1. The phloroglucinol-based carbon has narrower pore widths and higher pore volume than the lignin-derived counterpart and maintains a longer release time. Numerical modeling of the release kinetics data reveals that the diffusivities of all the drugs from lignin-based carbon media are of equivalent magnitude (10-22 to 10-24 m2 s-1). However, a tailored reduction of pore width in the sorbent reduces the diffusivity of smaller drug molecules (captopril) by an order of magnitude. Thus, engineered pore morphology in our synthesized carbon sorbent, along with its potential to tailor the chemistry of its interaction with sorbet, can be exploited for optimal delivery system of a preferred drug within its therapeutic level and below the level of toxicity.

  5. Improved oral bioavailability of glyburide by a self-nanoemulsifying drug delivery system.

    Science.gov (United States)

    Liu, Hongzhuo; Shang, Kuimao; Liu, Weina; Leng, Donglei; Li, Ran; Kong, Ying; Zhang, Tianhong

    2014-01-01

    The present study aimed at the development and characterisation of self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral bioavailability of poorly soluble glyburide. The solubility of glyburide was determined in various oils, surfactants and co-surfactants which were grouped into two different combinations to construct ternary phase diagrams. The formulations were evaluated for emulsification time, droplet size, zeta-potential, electrical conductivity and stability of nanoemulsions. The optimised SNEDDS loading with 5 mg/g glyburide comprised 55% Cremophor® RH 40, 15% propanediol and 30% Miglyol® 812, which rapidly formed fine oil-in-water nanoemulsions with 46 ± 4 nm particle size. Compared with the commercial micronised tablets (Glynase®PresTab®), enhanced in vitro release profiles of SNEDDS were observed, resulting in the 1.5-fold increase of AUC following oral administration of SNEDDS in fasting beagle dogs. These results indicated that SNEDDS is a promising drug delivery system for increasing the oral bioavailability of glyburide.

  6. Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals

    Directory of Open Access Journals (Sweden)

    Rajabalaya R

    2017-02-01

    Full Text Available Rajan Rajabalaya, Muhammad Nuh Musa, Nurolaini Kifli, Sheba R David PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Brunei Darussalam Abstract: Liquid crystal (LC dosage forms, particularly those using lipid-based lyotropic LCs (LLCs, have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations. Keywords: liquid crystal, drug delivery, controlled release, lyotropic, surfactants, drug localization

  7. Modern Prodrug Design for Targeted Oral Drug Delivery

    Directory of Open Access Journals (Sweden)

    Arik Dahan

    2014-10-01

    Full Text Available The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilicity and charge state, the modern approach to prodrug design considers molecular/cellular factors, e.g., membrane influx/efflux transporters and cellular protein expression and distribution. This novel targeted-prodrug approach is aimed to exploit carrier-mediated transport for enhanced intestinal permeability, as well as specific enzymes to promote activation of the prodrug and liberation of the free parent drug. The purpose of this article is to provide a concise overview of this modern prodrug approach, with useful successful examples for its utilization. In the past the prodrug approach used to be viewed as a last option strategy, after all other possible solutions were exhausted; nowadays this is no longer the case, and in fact, the prodrug approach should be considered already in the very earliest development stages. Indeed, the prodrug approach becomes more and more popular and successful. A mechanistic prodrug design that aims to allow intestinal permeability by specific transporters, as well as activation by specific enzymes, may greatly improve the prodrug efficiency, and allow for novel oral treatment options.

  8. Chitosan/lecithin liposomal nanovesicles as an oral insulin delivery system.

    Science.gov (United States)

    Al-Remawi, Mayyas; Elsayed, Amani; Maghrabi, Ibrahim; Hamaidi, Mohammad; Jaber, Nisrein

    2017-05-01

    In the present work, insulin-chitosan polyelectrolyte complexes associated to lecithin liposomes were investigated as a new carrier for oral delivery of insulin. The preparation was characterized in terms of particle size, zeta potential and encapsulation efficiency. Surface tension measurements revealed that insulin-chitosan polyelectrolyte complexes have some degree of hydrophobicity and should be added to lecithin liposomal dispersion and not the vice versa to prevent their adsorption on the surface. Stability of insulin was enhanced when it was associated to liposomes. Significant reduction of blood glucose levels was noticed after oral administration of liposomal preparation to streptozotocin diabetic rats compared to control. The hypoglycemic activity was more prolonged compared to subcutaneously administered insulin.

  9. Oral bioavailability enhancement and hepatoprotective effects of thymoquinone by self-nanoemulsifying drug delivery system.

    Science.gov (United States)

    Kalam, Mohd Abul; Raish, Mohammad; Ahmed, Ajaz; Alkharfy, Khalid M; Mohsin, Kazi; Alshamsan, Aws; Al-Jenoobi, Fahad I; Al-Mohizea, Abdullah M; Shakeel, Faiyaz

    2017-07-01

    Thymoquinone (TQ) is a poorly water soluble bioactive compound which shows poor oral bioavailability upon oral administration. Due to poor aqueous solubility and bioavailability of TQ, various self-nanoemulsifying drug delivery systems (SNEDDS) of TQ were developed and evaluated for enhancement of its hepatoprotective effects and oral bioavailability. Hepatoprotective and pharmacokinetic studies of TQ suspension and TQ-SNEDDS were carried out in rat models. Different SNEDDS formulations of TQ were developed and thermodynamically stable TQ-SNEDDS were characterized for physicochemical parameters and evaluated for drug release studies via dialysis membrane. Optimized SNEDDS formulation of TQ was selected for further evaluation of in vivo evaluation. In vivo hepatoprotective investigations showed significant hepatoprotective effects for optimized TQ-SNEDDS in comparison with TQ suspension. The oral administration of optimized SNEDDS showed significant improvement in in vivo absorption of TQ in comparison with TQ suspension. The relatively bioavailability of TQ was enhanced 3.87-fold by optimized SNEDDS in comparison with TQ suspension. The results of this research work indicated the potential of SNEDDS in enhancing relative bioavailability and therapeutic effects of natural bioactive compounds such as TQ. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Solid lipid nanoparticles as oral delivery systems of phenolic compounds: Overcoming pharmacokinetic limitations for nutraceutical applications.

    Science.gov (United States)

    Nunes, Sara; Madureira, Ana Raquel; Campos, Débora; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Manuela; Reis, Flávio

    2017-06-13

    Drug delivery systems, accompanied by nanoparticle technology, have recently emerged as prominent solutions to improve the pharmacokinetic properties, namely bioavailability, of therapeutic and nutraceutical agents. Solid lipid nanoparticles (SLNs) have received much attention from researchers due to their potential to protect or improve drug properties. SLNs have been reported to be an alternative system to traditional carriers, such as emulsions, liposomes, and polymeric nanoparticles. Phenolic compounds are widespread in plant-derived foodstuffs and therefore abundant in our diet. Over the last decades, phenolic compounds have received considerable attention due to several health promoting properties, mostly related to their antioxidant activity, which can have important implications for health. However, most of these compounds have been associated with poor bioavailability being poorly absorbed, rapidly metabolized and eliminated, which compromises its biological and pharmacological benefits. This paper provides a systematic review of the use of SLNs as oral delivery systems of phenolic compounds, in order to overcome pharmacokinetic limitations of these compounds and improved nutraceutical potential. In vitro studies, as well as works describing topical and oral treatments will be revisited and discussed. The classification, synthesis, and clinical application of these nanomaterials will be also considered in this review article.

  11. Development of coated nifedipine dry elixir as a long acting oral delivery with bioavailability enhancement.

    Science.gov (United States)

    Choi, Jae-Yoon; Jin, Su-Eon; Park, Youmie; Lee, Hyo-Jong; Park, Yohan; Maeng, Han-Joo; Kim, Chong-Kook

    2011-10-01

    To develop the long acting nifedipine oral delivery with bioavailability enhancement, a nifedipine dry elixir (NDE) containing nifedipine ethanol solution in dextrin shell was prepared using a spray-dryer, and then coated nifedipine dry elixir (CNDE) was prepared by coating NDE with Eudragit acrylic resin. The physical characteristics and bioavailability of NDE and CNDE were evaluated, and then compared to those of nifedipine powder. NDE and CNDE, which were spherical in shape, had about 6.64 and 8.68-8.75 μm of geometric mean diameters, respectively. The amount of nifedipine dissolved from NDE for 60 min increased about 7- and 40-fold compared to nifedipine powder in pH 1.2 simulated gastric fluid and pH 6.8 simulated intestinal fluid, respectively. Nifedipine released from CNDE was retarded in both dissolution media compared with that from NDE. After oral administration of NDE, the C(max) and AUC(0→8h) of nifedipine in rat increased about 13- and 7-fold, respectively, and the Tmax of nifedipine was reduced significantly compared with those after oral administration of nifedipine powder alone. The AUC(0→8h) and T(max) of nifedipine in CNDE increased markedly and the C(max) of nifedipine in CNDE was significantly reduced compared to those in NDE. It is concluded that CNDE, which could lower the initial burst-out plasma concentration and maintain the plasma level of nifedipine over a longer period with bioavailability enhancement, might be one of potential alternatives to the marketed long acting oral delivery system for nifedipine.

  12. Dual peptide-mediated targeted delivery of bioactive siRNAs to oral cancer cells in vivo.

    Science.gov (United States)

    Alexander-Bryant, Angela A; Zhang, Haiwen; Attaway, Christopher C; Pugh, William; Eggart, Laurence; Sansevere, Robert M; Andino, Lourdes M; Dinh, Lu; Cantini, Liliana P; Jakymiw, Andrew

    2017-09-01

    Despite significant advances in cancer treatment, the prognosis for oral cancer remains poor in comparison to other cancer types, including breast, skin, and prostate. As a result, more effective therapeutic modalities are needed for the treatment of oral cancer. Consequently, in the present study, we examined the feasibility of using a dual peptide carrier approach, combining an epidermal growth factor receptor (EGFR)-targeting peptide with an endosome-disruptive peptide, to mediate targeted delivery of small interfering RNAs (siRNAs) into EGFR-overexpressing oral cancer cells and induce silencing of the targeted oncogene, cancerous inhibitor of protein phosphatase 2A (CIP2A). Fluorescence microscopy, real-time PCR, Western blot analysis, and in vivo bioimaging of mice containing orthotopic xenograft tumors were used to examine the ability of the dual peptide carrier to mediate specific delivery of bioactive siRNAs into EGFR-overexpressing oral cancer cells/tissues. Co-complexation of the EGFR-targeting peptide, GE11R9, with the endosome-disruptive 599 peptide facilitated the specific uptake of siRNAs into oral cancer cells overexpressing EGFR in vitro with optimal gene silencing observed at a 60:30:1 (GE11R9:599:siRNA) molar ratio. Furthermore, when administered systemically to mice bearing xenograft oral tumors, this dual peptide complex mediated increased targeted delivery of siRNAs into tumor tissues in comparison to the 599 peptide alone and significantly enhanced CIP2A silencing. Herein we provide the first report demonstrating the clinical potential of a dual peptide strategy for siRNA-based therapeutics by synergistically mediating the effective targeting and delivery of bioactive siRNAs into EGFR-overexpressing oral cancer cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. In vitro characterization of microcontainers as an oral drug delivery system

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Keller, Stephan Sylvest; Jacobsen, J.

    We here present in vitro studies showing the promise of microcontainers (fabricated in either SU-8 or Poly(lactic acid) (PLLA)) as an oral drug delivery system for the poorly watersoluble drug, furosemide.......We here present in vitro studies showing the promise of microcontainers (fabricated in either SU-8 or Poly(lactic acid) (PLLA)) as an oral drug delivery system for the poorly watersoluble drug, furosemide....

  14. Emerging technologies to achieve oral delivery of GLP-1 and GLP-1 analogs for treatment of type 2 diabetes mellitus (T2DM

    Directory of Open Access Journals (Sweden)

    Shengwu Ma

    2017-04-01

    Full Text Available Glucagon-like peptide-1 (GLP-1 is a gastrointestinal (GI peptide hormone that stimulates insulin secretion, gene expression and β-cell proliferation, representing a potentially novel and promising therapeutic agent for the treatment of T2DM. DPP-IV-resistant, long-acting GLP-1 analogs have already been approved by FDA as injectable drugs for treating patients with T2DM. Oral delivery of therapeutic peptides and proteins would be preferred owing to advantages of lower cost, ease of administration and greater patient adherence. However, oral delivery of proteins can be affected by rapid enzymatic degradation in the GI tract and poor penetration across the intestinal membrane, which may require amounts that exceed practical consideration. Various production strategies have been explored to overcome challenges associated with the oral delivery of therapeutic peptides and proteins. The goal of this review is to provide an overview of the current state of progress made towards the oral delivery of GLP-1 and its analogs in the treatment of T2DM, with special emphasis on the development of plant and food-grade bacterial delivery systems. Recently, genetically engineered plants and food-grade bacteria have been increasingly explored as novel carrier systems for the oral delivery of peptide and protein drugs. These have a largely unexplored potential to serve both as an expression system and as a delivery vehicle for clinically relevant, cost effective therapeutics. As such, they hold great promise for human biopharmaceuticals and novel therapies against various diseases.

  15. Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

    Directory of Open Access Journals (Sweden)

    Priya Bawa

    2011-12-01

    Full Text Available Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.

  16. Nano-microdelivery systems for oral delivery of an active ingredient

    DEFF Research Database (Denmark)

    2014-01-01

    A composition for oral delivery of one or more active ingredients in the form of a lipid nano-micro-delivery system comprising a lipid nano-micro-structure comprising at least one lipid and at least one active ingredient, said at least one active ingredient being immobilized in said lipid nano...

  17. Oral ileocolonic drug delivery by the colopulse-system : A bioavailability study in healthy volunteers

    NARCIS (Netherlands)

    Schellekens, R C A; Stellaard, F; Olsder, G G; Woerdenbag, H J; Frijlink, H W; Kosterink, J G W

    2010-01-01

    The release profile of a novel oral ileocolonic drug delivery technology (ColoPulse-technology) was assessed by a combination of conventional kinetics of a marker substance in blood and site-specific signaling by stable isotope technology. Since ileocolonic delivery involves the drug release in a

  18. An overview of site-specific delivery of orally administered proteins ...

    African Journals Online (AJOL)

    Oral delivery of proteins and peptides poses one of the greatest challenges in controlled drug delivery due to degradation by proteolytic enzymes, poor membrane permeability and large molecular size. Therapeutic proteins/peptides are useful in correcting metabolic disorders (e.g., insulin in diabetes mellitus), ...

  19. Oral fast-dissolving drug delivery membranes prepared from electrospun polyvinylpyrrolidone ultrafine fibers

    International Nuclear Information System (INIS)

    Yu Dengguang; Shen Xiaxia; Zhu Limin; Branford-White, Chris; White, Kenneth; Annie Bligh, S W

    2009-01-01

    Oral fast-dissolving drug delivery membranes (FDMs) for poorly water-soluble drugs were prepared via electrospinning technology with ibuprofen as the model drug and polyvinylpyrrolidone (PVP) K30 as the filament-forming polymer and drug carrier. Results from differential scanning calorimetry, x-ray diffraction, and morphological observations demonstrated that ibuprofen was distributed in the ultrafine fibers in the form of nanosolid dispersions and the physical status of drug was an amorphous or molecular form, different from that of the pure drug and a physical mixture of PVP and ibuprofen. Fourier-transform infrared spectroscopy results illustrated that the main interactions between PVP and ibuprofen were mediated through hydrogen bonding. Pharmacotechnical tests showed that FDMs with different drug contents had almost the same wetting and disintegrating times, about 15 and 8 s, respectively, but significantly different drug dissolution rates due to the different physical status of the drug and the different drug-release-controlled mechanisms. 84.9% and 58.7% of ibuprofen was released in the first 20 s for FDMs with a drug-to-PVP ratio of 1:4 and 1:2, respectively. Electrospun ultrafine fibers have the potential to be used as solid dispersions to improve the dissolution profiles of poorly water-soluble drugs or as oral fast disintegrating drug delivery systems.

  20. Podoplanin expression in oral potentially malignant disorders and oral squamous cell carcinoma.

    Science.gov (United States)

    A G, Deepa; Janardanan-Nair, Bindu; B R, Varun

    2017-12-01

    Podoplanin is a type I transmembrane sialomucin-like glycoprotein that is specifically expressed in lymphatic endothelial cells. Studies have shown that assessment of podoplanin expression in the epithelial cells can be used to predict the malignant transformation of potentially malignant disorders and the metastatic tendency of primary head and neck squamous cell carcinoma. The aim of our study was to compare the expression of podoplanin in oral leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma with that in normal buccal mucosa by immunohistochemical methods. Immunohistochemical expression of podoplanin was analyzed in 20 cases each of oral leukoplakia, oral submucous fibrosis, oral squamous cell carcinoma and normal buccal mucosa, with monoclonal antibody D2-40. The expression of podoplanin was graded from grade 0-4. There was a statistically significant upregulation of the grades of podoplanin expression in oral squamous cell carcinoma(100%), oral submucous fibrosis (90%) and oral leukoplakia (65%) when compared to that in normal mucosa(35%). Podoplanin expression increased with decrease in grades of differentiation in oral squamous cell carcinoma . Podoplanin expression in the samples of oral submucous fibrosis was higher than that in oral leukoplakia. Evaluation of podoplanin expression in the epithelial cells of oral dysplastic lesions may provide valuable information to predict their risk of malignant transformation. Key words: Immunohistochemistry, Oral leukoplakia, Oral submucous fibrosis, Podoplanin, Squamous cell carcinoma.

  1. Design and development of microemulsion drug delivery system of acyclovir for improvement of oral bioavailability

    OpenAIRE

    Ghosh, Pradip Kumar; Majithiya, Rita J.; Umrethia, Manish L.; Murthy, Rayasa S. R.

    2006-01-01

    The main purpose of this work was to develop an oral microemulsion formulation for enhancing the bioavailability of acyclovir. A Labrafac-based microemulsion formulation with Labrasol as surfactant and Plurol Oleique as cosurfactant was developed for oral delivery of acyclovir. Phase behavior and solubilization capacity of the microemulsion system were characterized, and in vivo oral absorption of acyclovir from the microemulsion was investigated in rats. A single isotropic region, which was ...

  2. Optimising oral systems for the delivery of therapeutic proteins and ...

    African Journals Online (AJOL)

    Therapeutic proteins/peptides are mostly administered as parenteral (injectable) preparations as a result of their poor oral bioavailability which is due to degradation by proteolytic enzymes, poor membrane permeability and large molecular size. However, the oral route would be preferred to the parenteral administration ...

  3. Oral health technicians in Brazilian primary health care: potentials and constraints.

    Science.gov (United States)

    Aguiar, Dulce Maria Lucena de; Tomita, Nilce Emy; Machado, Maria de Fátima Antero Sousa; Martins, Cleide Lavieri; Frazão, Paulo

    2014-07-01

    Different perspectives on the role of mid-level workers in health care might represent a constraint to health policies. This study aimed to investigate how different agents view the participation of oral health technicians in direct activities of oral healthcare with the goal of understanding the related symbolic dispositions. Theoretical assumptions related to inter-professional collaboration and conflicts in the field of healthcare were used for this analysis. A researcher conducted 24 in-depth interviews with general dental practitioners, oral health technicians and local managers. The concepts of Pierre Bourdieu supported the data interpretation. The results indicated inter-professional relations marked by collaboration and conflict that reflect an action space related to different perspectives of primary care delivery. They also unveiled the symbolic devices related to the participation of oral health technicians that represent a constraint to the implementation of oral health policy, thus reducing the potential of primary health care in Brazil.

  4. Comparative study of chitosan- and PEG-coated lipid and PLGA nanoparticles as oral delivery systems for cannabinoids

    International Nuclear Information System (INIS)

    Durán-Lobato, Matilde; Martín-Banderas, Lucía; Gonçalves, Lídia M. D.; Fernández-Arévalo, Mercedes; Almeida, Antonio J.

    2015-01-01

    The cannabinoid derivative 1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone (CB13) has an important therapeutic potential as analgesic in chronic pain states that respond poorly to conventional drugs. However, the incidence of its mild-to-moderate and dose-dependent adverse effects, as well as its pharmacokinetic profile, actually holds back its use in humans. Thus, the use of a suitable carrier system for oral delivery of CB13 becomes an attractive strategy to develop a valuable therapy. Polymeric poly(lactic-co-glycolic) acid (PLGA) and lipid nanoparticles (LNPs) are widely studied delivery vehicles that improve the bioavailability of lipophilic compounds and present special interest in oral delivery. Their surface can be modified to improve the adhesion of particles to the oral mucosa and increase their circulation time in blood with additives such as chitosan (CS) and polyethylene glycol (PEG), which can be feasibly incorporated onto these particles in a post-production step. In this work, CS- and PEG-modified polymeric PLGA and LNPs were successfully obtained and comparatively evaluated under the same experimental conditions as oral carriers for CB13. All the formulations presented adequate blood compatibility and absence of cytotoxicity in Caco-2 cells. Coating with CS led to a higher interaction with Caco-2 cells and a limited uptake in THP1 cells, while coating with PEG led to a limited uptake in Caco-2 cells and strongly prevented THP1 cells uptake. The performance of each formulation is discussed as a comparison of the potential of these carriers as oral delivery systems of CB13

  5. Comparative study of chitosan- and PEG-coated lipid and PLGA nanoparticles as oral delivery systems for cannabinoids

    Science.gov (United States)

    Durán-Lobato, Matilde; Martín-Banderas, Lucía; Gonçalves, Lídia M. D.; Fernández-Arévalo, Mercedes; Almeida, Antonio J.

    2015-02-01

    The cannabinoid derivative 1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone (CB13) has an important therapeutic potential as analgesic in chronic pain states that respond poorly to conventional drugs. However, the incidence of its mild-to-moderate and dose-dependent adverse effects, as well as its pharmacokinetic profile, actually holds back its use in humans. Thus, the use of a suitable carrier system for oral delivery of CB13 becomes an attractive strategy to develop a valuable therapy. Polymeric poly(lactic-co-glycolic) acid (PLGA) and lipid nanoparticles (LNPs) are widely studied delivery vehicles that improve the bioavailability of lipophilic compounds and present special interest in oral delivery. Their surface can be modified to improve the adhesion of particles to the oral mucosa and increase their circulation time in blood with additives such as chitosan (CS) and polyethylene glycol (PEG), which can be feasibly incorporated onto these particles in a post-production step. In this work, CS- and PEG-modified polymeric PLGA and LNPs were successfully obtained and comparatively evaluated under the same experimental conditions as oral carriers for CB13. All the formulations presented adequate blood compatibility and absence of cytotoxicity in Caco-2 cells. Coating with CS led to a higher interaction with Caco-2 cells and a limited uptake in THP1 cells, while coating with PEG led to a limited uptake in Caco-2 cells and strongly prevented THP1 cells uptake. The performance of each formulation is discussed as a comparison of the potential of these carriers as oral delivery systems of CB13.

  6. Comparative study of chitosan- and PEG-coated lipid and PLGA nanoparticles as oral delivery systems for cannabinoids

    Energy Technology Data Exchange (ETDEWEB)

    Durán-Lobato, Matilde; Martín-Banderas, Lucía, E-mail: luciamartin@us.es [Universidad de Sevilla, Departmento Farmacia y Tecnología Farmacéutica, Facultad de Farmacia (España) (Spain); Gonçalves, Lídia M. D. [Universidade de Lisboa, Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculdade de Farmácia (Portugal); Fernández-Arévalo, Mercedes [Universidad de Sevilla, Departmento Farmacia y Tecnología Farmacéutica, Facultad de Farmacia (España) (Spain); Almeida, Antonio J. [Universidade de Lisboa, Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculdade de Farmácia (Portugal)

    2015-02-15

    The cannabinoid derivative 1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone (CB13) has an important therapeutic potential as analgesic in chronic pain states that respond poorly to conventional drugs. However, the incidence of its mild-to-moderate and dose-dependent adverse effects, as well as its pharmacokinetic profile, actually holds back its use in humans. Thus, the use of a suitable carrier system for oral delivery of CB13 becomes an attractive strategy to develop a valuable therapy. Polymeric poly(lactic-co-glycolic) acid (PLGA) and lipid nanoparticles (LNPs) are widely studied delivery vehicles that improve the bioavailability of lipophilic compounds and present special interest in oral delivery. Their surface can be modified to improve the adhesion of particles to the oral mucosa and increase their circulation time in blood with additives such as chitosan (CS) and polyethylene glycol (PEG), which can be feasibly incorporated onto these particles in a post-production step. In this work, CS- and PEG-modified polymeric PLGA and LNPs were successfully obtained and comparatively evaluated under the same experimental conditions as oral carriers for CB13. All the formulations presented adequate blood compatibility and absence of cytotoxicity in Caco-2 cells. Coating with CS led to a higher interaction with Caco-2 cells and a limited uptake in THP1 cells, while coating with PEG led to a limited uptake in Caco-2 cells and strongly prevented THP1 cells uptake. The performance of each formulation is discussed as a comparison of the potential of these carriers as oral delivery systems of CB13.

  7. Zein-alginate based oral drug delivery systems: Protection and release of therapeutic proteins.

    Science.gov (United States)

    Lee, Sungmun; Kim, Yeu-Chun; Park, Ji-Ho

    2016-12-30

    Reactive oxygen species (ROS) play an important role in the development of inflammatory bowel diseases. Superoxide dismutase (SOD) has a great therapeutic potential by scavenging superoxide that is one of ROS; however, in vivo application is limited especially when it is orally administered. SOD is easily degraded in vivo by the harsh conditions of gastrointestinal tract. Here, we design a zein-alginate based oral drug delivery system that protects SOD from the harsh conditions of gastrointestinal tract and releases it in the environment of the small intestine. SOD is encapsulated in zein-alginate nanoparticles (ZAN) via a phase separation method. We demonstrate that ZAN protect SOD from the harsh conditions of the stomach or small intestine condition. ZAN (200:40) at the weight ratio of 200mg zein to 40mg of alginate releases SOD in a pH dependent manner, and it releases 90.8±1.2% of encapsulated SOD at pH 7.4 in 2h, while only 11.4±0.4% of SOD was released at pH 1.3. The encapsulation efficiency of SOD in ZAN (200:40) was 62.1±2.0%. SOD in ZAN (200:40) reduced the intracellular ROS level and it saved 88.9±7.5% of Caco-2 cells from the toxic superoxide in 4 hours. Based on the results, zein-alginate based oral drug delivery systems will have numerous applications to drugs that are easily degradable in the harsh conditions of gastrointestinal tract. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Buccal bioadhesive drug delivery--a promising option for orally less efficient drugs.

    Science.gov (United States)

    Sudhakar, Yajaman; Kuotsu, Ketousetuo; Bandyopadhyay, A K

    2006-08-10

    Rapid developments in the field of molecular biology and gene technology resulted in generation of many macromolecular drugs including peptides, proteins, polysaccharides and nucleic acids in great number possessing superior pharmacological efficacy with site specificity and devoid of untoward and toxic effects. However, the main impediment for the oral delivery of these drugs as potential therapeutic agents is their extensive presystemic metabolism, instability in acidic environment resulting into inadequate and erratic oral absorption. Parenteral route of administration is the only established route that overcomes all these drawbacks associated with these orally less/inefficient drugs. But, these formulations are costly, have least patient compliance, require repeated administration, in addition to the other hazardous effects associated with this route. Over the last few decades' pharmaceutical scientists throughout the world are trying to explore transdermal and transmucosal routes as an alternative to injections. Among the various transmucosal sites available, mucosa of the buccal cavity was found to be the most convenient and easily accessible site for the delivery of therapeutic agents for both local and systemic delivery as retentive dosage forms, because it has expanse of smooth muscle which is relatively immobile, abundant vascularization, rapid recovery time after exposure to stress and the near absence of langerhans cells. Direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism leading to high bioavailability. Further, these dosage forms are self-administrable, cheap and have superior patient compliance. Developing a dosage form with the optimum pharmacokinetics is a promising area for continued research as it is enormously important and intellectually challenging. With the right dosage form design, local environment of the mucosa can be controlled and manipulated in order to

  9. Administração oral de peptídios e proteínas: I. Estratégias gerais para aumento da biodisponibilidade oral Oral delivery system for peptides and proteins: I. Approaches to improve oral bioavailability

    Directory of Open Access Journals (Sweden)

    Catarina Silva

    2002-06-01

    Full Text Available Existem, atualmente, centenas de peptídios e proteínas com ação terapêutica. Os obstáculos inerentes à sua administração oral têm impulsionado a investigação de estratégias capazes de os ultrapassar. Nesta revisão são abordados estes dois aspectos. A microencapsulação, pela sua versatilidade, sobressai entre as demais estratégias, afirmando-se como escolha potencial na administração oral de fármacos peptídicos.There are hundreds of peptides and proteins clinically relevant. The difficulties associated with their oral administration have been responsible for the major efforts in developing ways to improve oral bioavailability. Both these subjects are described in this review. The potentiality of microencapsulation presents this technique as a privileged approach for the oral delivery of peptide and protein drugs.

  10. Recent developments in oral lipid-based drug delivery

    DEFF Research Database (Denmark)

    Thomas, N.; Rades, T.; Müllertz, A.

    2013-01-01

    The increasing number of poorly water-soluble drugs in development in the pharmaceutical industry has sparked interest in novel drug delivery options such as lipid-based drug delivery systems (LbDDS). Several LbDDS have been marketed successfully and have shown superior and more reliable...... bioavailability compared to conventional formulations. However, some reluctance in the broader application of LbDDS still appears, despite the growing commercial interest in lipids as a drug delivery platform. This reluctance might at least in part be related to the complexity associated with the development...... and characterization of LbDDS. In particular, the lack of standardized test protocols can be identified as the major obstacles for the broader application of LbDDS. This review seeks to summarize recent approaches in the field of lipid-based drug delivery that try to elucidate some critical steps in their development...

  11. pH sensitive thiolated cationic hydrogel for oral insulin delivery.

    Science.gov (United States)

    Sonia, T A; Sharma, Chandra P

    2014-04-01

    The objective of this work is to study the efficacy of pH sensitive thiolated Polydimethylaminoethylmethacrylate for oral delivery of insulin. Synthesis of pH sensitive thiolated Polydimethylaminoethylmethacrylate (PDCPA) was carried out by crosslinking Polymethacrylic acid with thiolated Polydimethylaminoethylmethacrylate (PDCys) via carbodiimide chemistry. Prior to in vivo experiment, various physicochemical and biological characterisation were carried out to evaluate the efficacy of PDCPA. Modification was confirmed by IR and NMR spectroscopy. The particle size was found to be 284 nm with a zeta potential of 37.3+/-1.58 mV. Texture analyser measurements showed that PDCPA is more mucoadhesive than the parent polymer. Transepithelial electrical measurements showed a reduction of greater than 50% on incubation with PDCPA particles. Permeation studies showed that PDCPA is more permeable than the parent polymer. On in vivo evaluation on male diabetic rats, insulin loaded PDCPA exhibited a blood glucose reduction of 19%.

  12. Oral delivery of medications to companion animals: palatability considerations.

    Science.gov (United States)

    Thombre, Avinash G

    2004-06-23

    There is an increased need for highly palatable solid oral dosage forms for companion animals, which are voluntarily accepted by the dog or cat, either from a feeding bowl or from the outstretched hand of the pet owner. Such dosage forms represent an emerging trend in companion animal formulations with major impact on medical needs such as convenience and compliance, particularly for chronically administered medications, and on marketing needs such as product differentiation. This review focuses on the science of taste, food and flavor preferences of dogs and cats, and palatability testing, in the context of applying these principles to the development of an oral palatable tablet for companion animals.

  13. A facile nanoaggregation strategy for oral delivery of hydrophobic drugs by utilizing acid-base neutralization reactions

    International Nuclear Information System (INIS)

    Chen Huabing; Wan Jiangling; Wang Yirui; Mou Dongsheng; Liu Hongbin; Xu Huibi; Yang Xiangliang

    2008-01-01

    Nanonization strategies have been used to enhance the oral availability of numerous drugs that are poorly soluble in water. Exploring a facile nanonization strategy with highly practical potential is an attractive focus. Here, we report a novel facile nanoaggregation strategy for constructing drug nanoparticles of poorly soluble drugs with pH-dependent solubility by utilizing acid-base neutralization in aqueous solution, thus facilitating the exploration of nanonization in oral delivery for general applicability. We demonstrate that hydrophobic itraconazole dissolved in acid solution formed a growing core and aggregated into nanoparticles in the presence of stabilizers. The nanoparticles, with an average diameter of 279.3 nm and polydispersity index of 0.116, showed a higher dissolution rate when compared with the marketed formulation; the average dissolution was about 91.3%. The in vivo pharmacokinetic studies revealed that the nanoparticles had a rapid absorption and enhanced oral availability. The diet state also showed insignificant impact on the absorption of itraconazole from nanoparticles. This nanoaggregation strategy is a promising nanonization method with a facile process and avoidance of toxic organic solvents for oral delivery of poorly soluble drugs with pH-dependent solubility and reveals a highly practical potential in the pharmaceutical and chemical industries

  14. Silica-coated flexible liposomes as a nanohybrid delivery system for enhanced oral bioavailability of curcumin

    Directory of Open Access Journals (Sweden)

    Li C

    2012-12-01

    Full Text Available Chong Li, Yan Zhang, Tingting Su, Lianlian Feng, Yingying Long, Zhangbao ChenKey Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, ChinaAbstract: We investigated flexible liposomes as a potential oral drug delivery system. However, enhanced membrane fluidity and structural deformability may necessitate liposomal surface modification when facing the harsh environment of the gastrointestinal tract. In the present study, silica-coated flexible liposomes loaded with curcumin (CUR-SLs having poor water solubility as a model drug were prepared by a thin-film method with homogenization, followed by the formation of a silica shell by the sol-gel process. We systematically investigated the physical properties, drug release behavior, pharmacodynamics, and bioavailability of CUR-SLs. CUR-SLs had a mean diameter of 157 nm and a polydispersity index of 0.14, while the apparent entrapment efficiency was 90.62%. Compared with curcumin-loaded flexible liposomes (CUR-FLs without silica-coatings, CUR-SLs had significantly higher stability against artificial gastric fluid and showed more sustained drug release in artificial intestinal fluid as determined by in vitro release assays. The bioavailability of CUR-SLs and CUR-FLs was 7.76- and 2.35-fold higher, respectively, than that of curcumin suspensions. Silica coating markedly improved the stability of flexible liposomes, and CUR-SLs exhibited a 3.31-fold increase in bioavailability compared with CUR-FLs, indicating that silica-coated flexible liposomes may be employed as a potential carrier to deliver drugs with poor water solubility via the oral route with improved bioavailability.Keywords: silica, flexible liposome, oral bioavailability, curcumin

  15. Challenges in oral drug delivery in patients with esophageal dysphagia

    NARCIS (Netherlands)

    Kappelle, W.F.; Siersema, P.D.; Bogte, A.; Vleggaar, F.P.

    2016-01-01

    INTRODUCTION: Esophageal dysphagia is a commonly reported symptom with various benign and malignant causes. Esophageal dysphagia can impede intake of oral medication, which often poses a major challenge for both patients and physicians. The best way to address this challenge depends of the cause of

  16. In vivo evaluation of thiolated chitosan tablets for oral insulin delivery.

    Science.gov (United States)

    Millotti, Gioconda; Laffleur, Flavia; Perera, Glen; Vigl, Claudia; Pickl, Karin; Sinner, Frank; Bernkop-Schnürch, Andreas

    2014-10-01

    Chitosan-6-mercaptonicotinic acid (chitosan-6-MNA) is a thiolated chitosan with strong mucoadhesive properties and a pH-independent reactivity. This study aimed to evaluate the in vivo potential for the oral delivery of insulin. The comparison of the nonconjugated chitosan and chitosan-6-MNA was performed on several studies such as mucoadhesion, release, and in vivo studies. Thiolated chitosan formulations were both about 80-fold more mucoadhesive compared with unmodified ones. The thiolated chitosan tablets showed a sustained release for 5 h for the polymer of 20 kDa and 8 h for the polymer of 400 kDa. Human insulin was quantified in rats' plasma by means of ELISA specific for human insulin with no cross-reactivity with the endogenous insulin. In vivo results showed thiolation having a tremendous impact on the absorption of insulin. The absolute bioavailabilities were 0.73% for chitosan-6-MNA of 20 kDa and 0.62% for chitosan-6-MNA 400 kDa. The areas under the concentration-time curves (AUC) of chitosan-6-MNA formulations compared with unmodified chitosan were 4.8-fold improved for the polymer of 20 kDa and 21.02-fold improved for the polymer of 400 kDa. The improvement in the AUC with regard to the most promising aliphatic thiomer was up to 6.8-fold. Therefore, chitosan-6-MNA represents a promising excipient for the oral delivery of insulin. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  17. A potential peptide pathway from viruses to oral lichen planus.

    Science.gov (United States)

    Lucchese, Alberta

    2015-06-01

    Oral lichen planus is an idiopathic inflammatory disease of oral mucous membranes, characterized by an autoimmune epidermis attack by T cells. It remains unknown, however, how such aggressive T cells are activated in vivo to cause epidermal damage. This study analyzes the relationship at the peptide level between viruses and oral lichen planus disease. Four potentially immunogenic peptides (SSSSSSS, QEQLEKA, LLLLLLA, and MLSGNAG) are found to be shared between HCV, EBV, HHV-7, HSV-1, and CMV and three human proteins (namely pinin, desmoglein-3, and plectin). The described peptide sharing might be of help in deciphering the still unexplained immunopathogenic pathway that leads to oral lichen planus. © 2015 Wiley Periodicals, Inc.

  18. Evaluation of synthetic zeolites as oral delivery vehicle for anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Elham Khodaverdi

    2014-05-01

    Full Text Available Objective(s: In this research, zeolite X and zeolite Y were used as vehicle to prepare intestine targeted oral delivery systems of indomethacin and ibuprofen. Materials and Methods: A soaking procedure was implemented to encapsulate indomethacin or ibuprofen within synthetic zeolites. Gravimetric methods and IR spectra of prepared formulations were used to assess drug loading efficiencies into zeolite structures. Scanning Electron Microscopy (SEM was also utilized to determine morphologies changes in synthetic zeolites after drug loading. At the next stage, dissolution studies were used to predict the in vivo performance of prepared formulations at HCl 0.1 N and PBS pH 6.5 as simulated gastric fluid (SGF and simulated intestine fluid (SIF, respectively. Results: Drug loadings of prepared formulations was determined between 24-26 % w/w. Dissolution tests at SGF were shown that zeolites could retain acidic model drugs in their porous structures and can be able to limit their release into the stomach. On the other hand, all prepared formulations completely released model drugs during 3 hr in simulated intestine fluid. Conclusion: Obtained results indicated zeolites could potentially be able to release indomethacin and ibuprofen in a sustained and controlled manner and reduced adverse effects commonly accompanying oral administrations of NSAIDs.

  19. Drug permeability and mucoadhesion properties of thiolated trimethyl chitosan nanoparticles in oral insulin delivery.

    Science.gov (United States)

    Yin, Lichen; Ding, Jieying; He, Chunbai; Cui, Liming; Tang, Cui; Yin, Chunhua

    2009-10-01

    Trimethyl chitosan-cysteine conjugate (TMC-Cys) was synthesized in an attempt to combine the mucoadhesion and the permeation enhancing effects of TMC and thiolated polymers related to different mechanisms for oral absorption. TMC-Cys with various molecular weights (30, 200, and 500 kDa) and quaternization degrees (15 and 30%) was allowed to form polyelectrolyte nanoparticles with insulin through self-assembly, which demonstrated particle size of 100-200 nm, zeta potential of +12 to +18 mV, and high encapsulation efficiency. TMC-Cys/insulin nanoparticles (TMC-Cys NP) showed a 2.1-4.7-fold increase in mucoadhesion compared to TMC/insulin nanoparticles (TMC NP), which might be partly attributed to disulfide formation between TMC-Cys and mucin as evidenced by DSC measurement. Compared to insulin solution and TMC NP, TMC-Cys NP induced increased insulin transport through rat intestine by 3.3-11.7 and 1.7-2.6 folds, promoted Caco-2 cell internalization by 7.5-12.7 and 1.7-3.0 folds, and augmented uptake in Peyer's patches by 14.7-20.9 and 1.7-5.0 folds, respectively. Such results were further confirmed by in vivo experiment with the optimal TMC-Cys NP. Biocompatibility assessment revealed lack of toxicity of TMC-Cys NP. Therefore, self-assembled nanoparticles between TMC-Cys and protein drugs could be an effective and safe oral delivery system.

  20. Thiomers: potential excipients for non-invasive peptide delivery systems.

    Science.gov (United States)

    Bernkop-Schnürch, Andreas; Krauland, Alexander H; Leitner, Verena M; Palmberger, Thomas

    2004-09-01

    In recent years thiolated polymers or so-called thiomers have appeared as a promising alternative in the arena of non-invasive peptide delivery. Thiomers are generated by the immobilisation of thiol-bearing ligands to mucoadhesive polymeric excipients. By formation of disulfide bonds with mucus glycoproteins, the mucoadhesive properties of these polymers are improved up to 130-fold. Due to formation of inter- and intramolecular disulfide bonds within the thiomer itself, dosage forms such as tablets or microparticles display strong cohesive properties resulting in comparatively higher stability, prolonged disintegration times and a more controlled release of the embedded peptide drug. The permeation of peptide drugs through mucosa can be improved by the use of thiolated polymers. Additionally some thiomers exhibit improved inhibitory properties towards peptidases. The efficacy of thiomers in non-invasive peptide delivery could be demonstrated by various in vivo studies. Tablets comprising a thiomer and pegylated insulin, for instance, resulted in a pharmacological efficacy of 7% after oral application to diabetic mice. Furthermore, a pharmacological efficacy of 1.3% was achieved in rats by oral administration of calcitonin tablets comprising a thiomer. Human growth hormone in a thiomer-gel was applied nasally to rats and led to a bioavailability of 2.75%. In all these studies, formulations comprising the corresponding unmodified polymer had only a marginal or no effect. According to these results drug carrier systems based on thiomers seem to be a promising tool for non-invasive peptide drug delivery.

  1. A combination of complexation and self-nanoemulsifying drug delivery system for enhancing oral bioavailability and anticancer efficacy of curcumin.

    Science.gov (United States)

    Shukla, Mahendra; Jaiswal, Swati; Sharma, Abhisheak; Srivastava, Pradeep Kumar; Arya, Abhishek; Dwivedi, Anil Kumar; Lal, Jawahar

    2017-05-01

    Curcumin, the golden spice from Indian saffron, has shown chemoprotective action against many types of cancer including breast cancer. However, poor oral bioavailability is the major hurdle in its clinical application. In the recent years, self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising tool to improve the oral absorption and enhancing the bioavailability of poorly water-soluble drugs. In this context, complexation with lipid carriers like phospholipid has also shown the tremendous potential to improve the solubility and therapeutic efficacy of certain drugs with poor oral bioavailability. In the present investigation, a systematic combination of both the approaches is utilized to prepare the phospholipid complex of curcumin and facilitate its incorporation into SNEDDS. The combined use of both the approaches has been explored for the first time to enhance the oral bioavailability and in turn increase the anticancer activity of curcumin. As evident from the pharmacokinetic studies and in situ single pass intestinal perfusion studies in Sprague-Dawley rats, the optimized SNEDDS of curcumin-phospholipid complex has shown enhanced oral absorption and bioavailability of curcumin. The cytotoxicity study in metastatic breast carcinoma cell line has shown the enhancement of cytotoxic action by 38.7%. The primary tumor growth reduction by 58.9% as compared with the control group in 4T1 tumor-bearing BALB/c mice further supported the theory of enhancement of anticancer activity of curcumin in SNEDDS. The developed formulation can be a potential and safe carrier for the oral delivery of curcumin.

  2. Improved Oral Bioavailability Using a Solid Self-Microemulsifying Drug Delivery System Containing a Multicomponent Mixture Extracted from Salvia miltiorrhiza

    Directory of Open Access Journals (Sweden)

    Xiaolin Bi

    2016-04-01

    Full Text Available The active ingredients of salvia (dried root of Salvia miltiorrhiza include both lipophilic (e.g., tanshinone IIA, tanshinone I, cryptotanshinone and dihydrotanshinone I and hydrophilic (e.g., danshensu and salvianolic acid B constituents. The low oral bioavailability of these constituents may limit their efficacy. A solid self-microemulsifying drug delivery system (S-SMEDDS was developed to load the various active constituents of salvia into a single drug delivery system and improve their oral bioavailability. A prototype SMEDDS was designed using solubility studies and phase diagram construction, and characterized by self-emulsification performance, stability, morphology, droplet size, polydispersity index and zeta potential. Furthermore, the S-SMEDDS was prepared by dispersing liquid SMEDDS containing liposoluble extract into a solution containing aqueous extract and hydrophilic polymer, and then freeze-drying. In vitro release of tanshinone IIA, salvianolic acid B, cryptotanshinone and danshensu from the S-SMEDDS was examined, showing approximately 60%–80% of each active component was released from the S-SMEDDS in vitro within 20 min. In vivo bioavailability of these four constituents indicated that the S-SMEDDS showed superior in vivo oral absorption to a drug suspension after oral administration in rats. It can be concluded that the novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of both lipophilic and hydrophilic constituents of salvia. Thus, the S-SMEDDS can be regarded as a promising new method by which to deliver salvia extract, and potentially other multicomponent drugs, by the oral route.

  3. Intradermal delivery of vaccines: potential benefits and current challenges

    Science.gov (United States)

    Hickling, JK; Jones, KR; Friede, M; Chen, D; Kristensen, D

    2011-01-01

    Abstract Delivery of vaccine antigens to the dermis and/or epidermis of human skin (i.e. intradermal delivery) might be more efficient than injection into the muscle or subcutaneous tissue, thereby reducing the volumes of antigen. This is known as dose-sparing and has been demonstrated in clinical trials with some, but not all, vaccines. Dose-sparing could be beneficial to immunization programmes by potentially reducing the costs of purchase, distribution and storage of vaccines; increasing vaccine availability and effectiveness. The data obtained with intradermal delivery of some vaccines are encouraging and warrant further study and development; however significant gaps in knowledge and operational challenges such as reformulation, optimizing vaccine presentation and development of novel devices to aid intradermal vaccine delivery need to be addressed. Modelling of the costs and potential savings resulting from intradermal delivery should be done to provide realistic expectations of the potential benefits and to support cases for investment. Implementation and uptake of intradermal vaccine delivery requires further research and development, which depends upon collaboration between multiple stakeholders in the field of vaccination. PMID:21379418

  4. Cost of goods sold and total cost of delivery for oral and parenteral vaccine packaging formats.

    Science.gov (United States)

    Sedita, Jeff; Perrella, Stefanie; Morio, Matt; Berbari, Michael; Hsu, Jui-Shan; Saxon, Eugene; Jarrahian, Courtney; Rein-Weston, Annie; Zehrung, Darin

    2018-03-14

    Despite limitations of glass packaging for vaccines, the industry has been slow to implement alternative formats. Polymer containers may address many of these limitations, such as breakage and delamination. However, the ability of polymer containers to achieve cost of goods sold (COGS) and total cost of delivery (TCOD) competitive with that of glass containers is unclear, especially for cost-sensitive low- and lower-middle-income countries. COGS and TCOD models for oral and parenteral vaccine packaging formats were developed based on information from subject matter experts, published literature, and Kenya's comprehensive multiyear plan for immunization. Rotavirus and inactivated poliovirus vaccines (IPV) were used as representative examples of oral and parenteral vaccines, respectively. Packaging technologies evaluated included glass vials, blow-fill-seal (BFS) containers, preformed polymer containers, and compact prefilled auto-disable (CPAD) devices in both BFS and preformed formats. For oral vaccine packaging, BFS multi-monodose (MMD) ampoules were the least expensive format, with a COGS of $0.12 per dose. In comparison, oral single-dose glass vials had a COGS of $0.40. BFS MMD ampoules had the lowest TCOD of oral vaccine containers at $1.19 per dose delivered, and ten-dose glass vials had a TCOD of $1.61 per dose delivered. For parenteral vaccines, the lowest COGS was achieved with ten-dose glass vials at $0.22 per dose. In contrast, preformed CPAD devices had the highest COGS at $0.60 per dose. Ten-dose glass vials achieved the lowest TCOD of the parenteral vaccine formats at $1.56 per dose delivered. Of the polymer containers for parenteral vaccines, BFS MMD ampoules achieved the lowest TCOD at $1.89 per dose delivered, whereas preformed CPAD devices remained the most expensive format, at $2.25 per dose delivered. Given their potential to address the limitations of glass and reduce COGS and TCOD, polymer containers deserve further consideration as alternative

  5. PEG-lipid-PLGA hybrid nanoparticles loaded with berberine-phospholipid complex to facilitate the oral delivery efficiency.

    Science.gov (United States)

    Yu, Fei; Ao, Mingtao; Zheng, Xiao; Li, Nini; Xia, Junjie; Li, Yang; Li, Donghui; Hou, Zhenqing; Qi, Zhongquan; Chen, Xiao Dong

    2017-11-01

    The natural product berberine (BBR), present in various plants, arouses great interests because of its numerous pharmacological effects. However, the further development and application of BBR had been hampered by its poor oral bioavailability. In this work, we report on polymer-lipid hybrid nanoparticles (PEG-lipid-PLGA NPs) loaded with BBR phospholipid complex using a solvent evaporation method for enhancing the oral BBR efficiency. The advantage of this new drug delivery system is that the BBR-soybean phosphatidylcholine complex (BBR-SPC) could be used to enhance the liposolubility of BBR and improve the affinity with the biodegradable polymer to increase the drug-loading capacity and controlled/sustained release. The entrapment efficiency of the PEG-lipid-PLGA NPs/BBR-SPC was observed to approach approximately 89% which is more than 2.4 times compared with that of the PEG-lipid-PLGA NPs/BBR. To the best of our knowledge, this is the first report on using polymer material for effective encapsulation of BBR to improve its oral bioavailability. The prepared BBR delivery systems demonstrated a uniform spherical shape, a well-dispersed core-shell structure and a small particle size (149.6 ± 5.1 nm). The crystallographic and thermal analysis has indicated that the BBR dispersed in the PEG-lipid-PLGA NPs matrix is in an amorphous form. More importantly, the enhancement in the oral relative bioavailability of the PEG-lipid-PLGA NPs/BBR-SPC was ∼343% compared with that of BBR. These positive results demonstrated that PEG-lipid-PLGA NPs/BBR-SPC may have the potential for facilitating the oral drug delivery of BBR.

  6. Solid Phospholipid Dispersions for Oral Delivery of Poorly Soluble Drugs

    DEFF Research Database (Denmark)

    Fong, Sophia Yui Kau; Martins, Susana A. M.; Brandl, Martin

    2016-01-01

    Celecoxib (CXB) is a Biopharmaceutical Classification System class II drug in which its oral bioavailability is limited by poor aqueous solubility. Although a range of formulations aiming to increase the solubility of CXB have been developed, it is not completely understood, whether (1) an increase...... the importance of evaluating both, solubility and permeability, and the use of biorelevant medium for testing the candidate-enabling performance of liposomal formulations. Mechanisms at molecular level that may explain the effect of PL formulations on the permeability of CXB are also discussed....

  7. Stimuli sensitive polymethacrylic acid microparticles (PMAA)--oral insulin delivery.

    Science.gov (United States)

    Victor, Sunita Prem; Sharma, Chandra P

    2002-10-01

    This study investigated polymethacrylic acid (PMAA) microparticles for controlled release of Insulin in oral administration. The microparticles were characterised by scanning electron microscopy (SEM) for morphological studies. The swelling behaviour and drug release profile in various pH media were studied. The % swelling of gels was found to be inversely related to the amount of crosslinker added. Inclusion complex of betaCD and Insulin was studied using polyacrylamide gel electrophoresis (PAGE). Optimum complexation was obtained in the ratio 100 mg betaCD: 200 IU Insulin. The release pattern of Insulin from Insulin-betaCD complex encapsulated PMAA microparticles showed release of Insulin for more than seven hours.

  8. Nanoencapsulation of Insulin into Zirconium Phosphate for Oral Delivery Applications

    Science.gov (United States)

    Díaz, Agustín; David, Amanda; Pérez, Riviam; González, Millie L.; Báez, Adriana; Wark, Stacey E.; Zhang, Paul; Clearfield, Abraham; Colón, Jorge L.

    2010-01-01

    The encapsulation of insulin into different kinds of materials for non-invasive delivery is an important field of study because of the many drawbacks of painful needle and syringe delivery such as physiological stress, infection, and local hypertrophy, among others.1 A stable, robust, non-toxic, and viable non-invasive carrier for insulin delivery is needed. We present a new approach for protein nanoencapsulation using layered zirconium phosphate (ZrP) nanoparticles produced without any preintercalator present. The use of ZrP without preintercalators produces a highly pure material, without any kinds of contaminants, such as the preintercalator, which can be noxious. Cytotoxicity cell viability in vitro experiments for the ZrP nanoparticles show that ZrP is not toxic, or harmful, in a biological environment, as previously reported for rats.2 Contrary to previous preintercalator-based methods, we show that insulin can be nanoencapsulated in ZrP if a highly hydrate phase of ZrP with an interlayer distance of 10.3 Å (10.3 Å-ZrP or θ-ZrP) is used as precursor. The intercalation of insulin into ZrP produced a new insulin-intercalated ZrP phase with a ca. 27 Å interlayer distance, as determined by X-ray powder diffraction, demonstrating a successful nanoencapsulation of the hormone. The in vitro release profile of the hormone after the intercalation was determined and circular dichroism was used to study the hormone stability upon intercalation and release. The insulin remains stable in the layered material, at room temperature, for a considerable amount of time, improving the shell life of the peptidic hormone. This type of materials represents a strong candidate to develop a non-invasive insulin carrier for the treatment of diabetes mellitus. PMID:20707305

  9. Oral delivery of bioencapsulated proteins across blood-brain and blood-retinal barriers.

    Science.gov (United States)

    Kohli, Neha; Westerveld, Donevan R; Ayache, Alexandra C; Verma, Amrisha; Shil, Pollob; Prasad, Tuhina; Zhu, Ping; Chan, Sic L; Li, Qiuhong; Daniell, Henry

    2014-03-01

    Delivering neurotherapeutics to target brain-associated diseases is a major challenge. Therefore, we investigated oral delivery of green fluorescence protein (GFP) or myelin basic protein (MBP) fused with the transmucosal carrier cholera toxin B subunit (CTB), expressed in chloroplasts (bioencapsulated within plant cells) to the brain and retinae of triple transgenic Alzheimer's disease (3×TgAD) mice, across the blood-brain barriers (BBB) and blood-retinal barriers (BRB). Human neuroblastoma cells internalized GFP when incubated with CTB-GFP but not with GFP alone. Oral delivery of CTB-MBP in healthy and 3×TgAD mice shows increased MBP levels in different regions of the brain, crossing intact BBB. Thioflavin S-stained amyloid plaque intensity was reduced up to 60% by CTB-MBP incubation with human AD and 3×TgAD mice brain sections ex vivo. Amyloid loads were reduced in vivo by 70% in hippocampus and cortex brain regions of 3×TgAD mice fed with bioencapsulated CTB-MBP, along with reduction in the ratio of insoluble amyloid β 42 (Aβ42) to soluble fractions. CTB-MBP oral delivery reduced Aβ42 accumulation in retinae and prevented loss of retinal ganglion cells in 3×TgAD mice. Lyophilization of leaves increased CTB-MBP concentration by 17-fold and stabilized it during long-term storage in capsules, facilitating low-cost oral delivery of therapeutic proteins across the BBB and BRB.

  10. Self-assembled nanoparticles based on amphiphilic chitosan derivative and arginine for oral curcumin delivery

    Directory of Open Access Journals (Sweden)

    Raja MA

    2016-09-01

    Full Text Available Mazhar Ali Raja, Shah Zeenat, Muhammad Arif, Chenguang Liu College of Marine Life Science, Ocean University of China, Qingdao, Shandong, People’s Republic of China Abstract: Curcumin (Cur is a striking anticancer agent, but its low aqueous solubility, poor absorption, hasty metabolism, and elimination limit its oral bioavailability and consequently hinder its development as a drug. To redress these limitations, amphiphilic chitosan (CS conjugate with improved mucoadhesion and solubility over a wider pH range was developed by modification with hydrophobic acrylonitrile (AN and hydrophilic arginine (Arg; the synthesized conjugate (AN–CS–Arg, which was well characterized by Fourier transform infrared and 1H nuclear magnetic resonance spectroscopy. Results of critical aggregation concentration revealed that the AN–CS–Arg conjugate had low critical aggregation concentration and was prone to form self-assembled nanoparticles (NPs in aqueous medium. Cur-encapsulated AN–CS–Arg NPs (AN–CS–Arg/Cur NPs were developed by a simple sonication method and characterized for the physicochemical parameters such as zeta potential, particle size, and drug encapsulation. The results showed that zeta potential of the prepared NPs was 40.1±2.81 mV and the average size was ~218 nm. A considerable improvement in the aqueous solubility of Cur was observed after encapsulation into AN–CS–Arg/Cur NPs. With the increase in Cur concentration, loading efficiency increased but encapsulation efficiency decreased. The in vitro release profile exhibited sustained release pattern from the AN–CS–Arg/Cur NPs in typical biological buffers. The ex vivo mucoadhesion study revealed that AN–CS–Arg/Cur NPs had greater mucoadhesion than the control CS NPs. Compared with free Cur solution, AN–CS–Arg/Cur NPs showed stronger dose-dependent cytotoxicity against HT-29 cells. In addition, it was observed that cell uptake of AN–CS–Arg/Cur NPs was much higher

  11. Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics

    Directory of Open Access Journals (Sweden)

    Gavin A

    2015-02-01

    Full Text Available Amy Gavin,1 Jimmy TH Pham,2 Dawei Wang,2 Bill Brownlow,3 Tamer A Elbayoumi3 1College of Dental Medicine, 2Arizona College of Osteopathic Medicine, 3Department of Pharmaceutical Sciences, College of Pharmacy-Glendale, Midwestern University, Glendale, AZ, USA Abstract: Oral cavity and oropharyngeal cancers are considered the eighth most common cancer worldwide, with relatively poor prognosis (62% of patients surviving 5 years, after diagnosis. The aim of this study was to develop a proof-of-concept mucoadhesive lozenge/buccal tablet, as a potential platform for direct sustained delivery of therapeutic antimitotic nanomedicines. Our system would serve as an adjuvant therapy for oral cancer patients undergoing full-scale diagnostic and operative treatment plans. We utilized lipid-based nanocarriers, namely nanoemulsions (NEs, containing mixed-polyethoxylated emulsifiers and a tocopheryl moiety–enriched oil phase. Prototype NEs, loaded with the proapoptotic lipophilic drug genistein (Gen, were further processed into buccal tablet formulations. The chitosan polyelectrolyte solution overcoat rendered NE droplets cationic, by acting as a mucoadhesive interfacial NE layer. With approximate size of 110 nm, the positively charged chitosan-layered NE (+25 mV vs negatively charged chitosan-free/primary aqueous NE (-28 mV exhibited a controlled-release profile and effective mucoadhesion for liquid oral spray prototypes. When punch-pressed, porous NE-based buccal tablets were physically evaluated for hardness, friability, and swelling in addition to ex vivo tissue mucoadhesion force and retention time measurements. Chitosan-containing NE tablets were found equivalent to primary NE and placebo tablets in compression tests, yet significantly superior in all ex vivo adhesion and in vitro release assays (P≤0.05. Following biocompatibility screening of prototype chitosan-layered NEs, substantial anticancer activity of selected cationic Gen-loaded NE

  12. The use of thiolated polymers as carrier matrix in oral peptide delivery--proof of concept.

    Science.gov (United States)

    Bernkop-Schnürch, Andreas; Pinter, Yvonne; Guggi, Davide; Kahlbacher, Hermann; Schöffmann, Gudrun; Schuh, Maximilian; Schmerold, Ivo; Del Curto, Maria Dorly; D'Antonio, Mauro; Esposito, Pierandrea; Huck, Christian

    2005-08-18

    It was the aim of this study to develop an oral delivery system for the peptide drug antide. The stability of the therapeutic peptide towards gastrointestinal peptidases was evaluated. The therapeutic agent and the permeation mediator glutathione were embedded in the thiolated polymer chitosan-4-thio-butylamidine conjugate (chitosan-TBA conjugate) and compressed to tablets. Drug release studies were performed in the dissolution test apparatus according to the Pharmacopoeia Europea using the paddle method and demineralized water as release medium. In order to avoid mucoadhesion of these delivery systems already in the oral cavity and oesophagus tablets were coated with a triglyceride. These tablets were orally given to pigs (weight: 50+/-2 kg; Edelschwein Pietrain). Moreover, antide was administered intravenously, subcutaneously and orally in solution. Results showed stability of antide towards pepsin, trypsin and chymotrypsin. In contrast, antide was rapidly degraded by elastase. Consequently a stomach-targeted delivery system was designed. Drug release studies demonstrated an almost zero-order controlled release of antide over 8 h. In vivo studies demonstrated a relative bioavailability of 34.4% for the subcutaneous administration. Oral administration of antide in solution led to no detectable concentrations of the drug in plasma at all. In contrast, administering antide being incorporated in the thiolated polymer resulted in a significant uptake of the peptide. The absolute and relative bioavailability was determined to be 1.1% and 3.2%, respectively.

  13. Calcium phosphate-PEG-insulin-casein (CAPIC) particles as oral delivery systems for insulin.

    Science.gov (United States)

    Morçöl, T; Nagappan, P; Nerenbaum, L; Mitchell, A; Bell, S J D

    2004-06-11

    An oral delivery system for insulin was developed and functional activity was tested in a non-obese diabetic (NOD) mice model. Calcium phosphate particles containing insulin was synthesized in the presence of PEG-3350 and modified by aggregating the particles with caseins to obtain the calcium phosphate-PEG-insulin-casein (CAPIC) oral insulin delivery system. Single doses of CAPIC formulation were tested in NOD mice under fasting or fed conditions to evaluate the glycemic activity. The blood glucose levels were monitored every 1-2h for 12h following the treatments using an ACCU CHECK blood glucose monitoring system. Orally administered and subcutaneously injected free insulin solution served as controls in the study. Based on the results obtained we propose that: (1). the biological activity of insulin is preserved in CAPIC formulation; (2). insulin in CAPIC formulations, but not the free insulin, displays a prolonged hypoglycemic effect after oral administration to diabetic mice; (3). CAPIC formulation protects insulin from degradation while passing through the acidic environment of the GI track until it is released in the less acidic environment of the intestines where it can be absorbed in its biologically active form; (4). CAPIC formulation represents a new and unique oral delivery system for insulin and other macromolecules.

  14. On prilled Nanotubes-in-Microgel Oral Systems for protein delivery.

    Science.gov (United States)

    de Kruif, Jan Kendall; Ledergerber, Gisela; Garofalo, Carla; Fasler-Kan, Elizaveta; Kuentz, Martin

    2016-04-01

    Newly discovered active macromolecules are highly promising for therapy, but poor bioavailability hinders their oral use. Microencapsulation approaches, such as protein prilling into microspheres, may enable protection from gastrointestinal (GI) enzymatic degradation. This would increase bioavailability mainly for local delivery to GI lumen or mucosa. This work's purpose was to design a novel architecture, namely a Nanotubes-in-Microgel Oral System, by prilling for protein delivery. Halloysite nanotubes (HNT) were selected as orally acceptable clay particles and their lumen was enlarged by alkaline etching. This chemical modification increased the luminal volume to a mean of 216.3 μL g(-1) (+40.8%). After loading albumin as model drug, the HNT were entrapped in microgels by prilling. The formation of Nanoparticles-in-Microsphere Oral System (NiMOS) yielded entrapment efficiencies up to 63.2%. NiMOS shape was spherical to toroidal, with a diameter smaller than 320 μm. Release profiles depended largely on the employed system and HNT type. Protein stability was determined throughout prilling and after in vitro enzymatic degradation. Prilling did not harm protein structure, and NiMOS demonstrated higher enzymatic protection than pure nanotubes or microgels, since up to 82% of BSA remained unscathed after in vitro digestion. Therefore, prilled NiMOS was shown to be a promising and flexible multi-compartment system for oral (local) macromolecular delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Sex differences in the gastrointestinal tract of rats and the implications for oral drug delivery.

    Science.gov (United States)

    Afonso-Pereira, Francisco; Dou, Liu; Trenfield, Sarah J; Madla, Christine M; Murdan, Sudaxshina; Sousa, Jõao; Veiga, Francisco; Basit, Abdul W

    2018-03-30

    Pre-clinical research often uses rodents as animal models to guide the selection of appropriate oral drug and dose selection in humans. However, traditionally, such research fails to consider the gastrointestinal differences between the sexes of rats and the impact on oral drug delivery. This study aimed to identify and characterise the potential sex-related differences in the gastrointestinal environment of sacrificed male and female Wistar rats. Their gastrointestinal tracts were excised and segmented into the stomach, duodenum, jejunum, ileum, caecum and colon. The respective contents and tissue sections were collected and analysed for pH, buffer capacity, surface tension, osmolality and relative P-glycoprotein (P-gp) expression. The pH in the stomach of females was found to be lower than in males. Female rats also exhibited a higher buffer capacity in the caecum and colon when compared with their male counterparts. Males were found to have a higher osmolality than females in the duodenum, ileum and colon. Significant sex differences (p < 0.05) in surface tension were observed in the ileum, where females exhibited a higher surface tension. Interestingly, female rats displayed significantly higher relative P-gp expression levels (p < 0.05) when compared with male rats in the duodenum (1.24 ± 0.85 vs. 0.36 ± 0.26), jejunum (1.45 ± 0.88 vs. 0.38 ± 0.26) and ileum (0.92 ± 0.43 vs. 0.40 ± 0.18) but not in the colon (0.5 ± 0.32 vs. 0.33 ± 0.16) segments. The work reported has demonstrated the stark physiological differences between male and female rats at a physiological level, indicating how the 'sex of the gut' could influence oral drug delivery. These findings, therefore, are of critical importance in pre-clinical research and drug development. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Self-assembly of green tea catechin derivatives in nanoparticles for oral lycopene delivery.

    Science.gov (United States)

    Li, Weikun; Yalcin, Murat; Lin, Qishan; Ardawi, Mohammed-Salleh M; Mousa, Shaker A

    2017-02-28

    Lycopene is a natural anti-oxidant that has attracted much attention due to its varied applications such as protection against loss of bone mass, chronic diseases, skin cancer, prostate cancer, and cardiovascular disease. However, high instability and extremely low oral bioavailability limit its further clinical development. We selected a green tea catechin derivative, oligomerized (-)-epigallocatechin-3-O-gallate (OEGCG) as a carrier for oral lycopene delivery. Lycopene-loaded OEGCG nanoparticles (NPs) were prepared by a nano-precipitation method, followed by coating with chitosan to form a shell. This method not only can easily control the size of the NP to be around 200nm to improve its bioavailability, but also can effectively protect the lycopene against degradation due to EGCG's anti-oxidant property. OEGCG was carefully characterized with nuclear magnetic resonance spectroscopy and mass spectrometry. Lycopene-loaded polylactic-co-glycolic acid (PLGA) NPs were prepared by the same method. Chitosan-coated OEGCG/lycopene NPs had a diameter of 152±32nm and a ζ-potential of 58.3±4.2mv as characterized with transmission electron microscopy and dynamic light scattering. The loading capacity of lycopene was 9% and encapsulation efficiency was 89%. FT-IR spectral analysis revealed electrostatic interaction between OEGCG and chitosan. Freeze drying of the NPs was also evaluated as a means to improve shelf life. Dynamic light scattering data showed that no aggregation occurred, and the size of the NP increased 1.2 times (S f /S i ratio) in the presence of 10% sucrose after freeze drying. The in vitro release study showed slow release of lycopene in simulated gastric fluid at acidic pH and faster release in simulated intestinal fluid. In an in vivo study in mice, lycopene pharmacokinetic parameters were improved by lycopene/OEGCG/chitosan NPs, but not improved by lycopene/PLGA/chitosan NPs. The self-assembled nanostructure of OEGCG combined with lycopene may be a

  17. PLGA-Chitosan nanoparticle-mediated gene delivery for oral cancer treatment: A brief review

    Science.gov (United States)

    Bakar, L. M.; Abdullah, M. Z.; Doolaanea, A. A.; Ichwan, S. J. A.

    2017-08-01

    Cancer becomes a serious issue on society with increasing of their growth and proliferation, either in well economic developed countries or not. Recent years, oral cancer is one of the most threatening diseases impairing the quality of life of the patient. Scientists have emphasised on application of gene therapy for oral cancer by using nanoparticle as transportation vectors as a new alternative platform in order to overcome the limitations of conventional approaches. In modern medicine, nanotechnologies’ application, such as nanoparticles-mediated gene delivery, is one of promising tool for therapeutic devices. The objective of this article is to present a brief review summarizes on the current progress of nanotechnology-based gene delivery treatment system targeted for oral cancer.

  18. Bicontinuous cubic liquid crystalline nanoparticles for oral delivery of Doxorubicin

    DEFF Research Database (Denmark)

    Swarnakar, Nitin K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    PURPOSE: The present study explores the potential of bicontinous cubic liquid crystalline nanoparticles (LCNPs) for improving therapeutic potential of doxorubicin. METHODS: Phytantriol based Dox-LCNPs were prepared using hydrotrope method, optimized for various formulation components, process...

  19. The role of chitosan on oral delivery of peptide-loaded nanoparticle formulation.

    Science.gov (United States)

    Wong, Chun Y; Al-Salami, Hani; Dass, Crispin R

    2017-12-01

    Therapeutic peptides are conventionally administered via subcutaneous injection. Chitosan-based nanoparticles are gaining increased attention for their ability to serve as a carrier for oral delivery of peptides and vaccination. They offered superior biocompatibiltiy, controlled drug release profile and facilitated gastrointestinal (GI) absorption. The encapsulated peptides can withstand enzymatic degradation and various pH. Chitosan-based nanoparticles can also be modified by ligand conjugation to the surface of nanoparticle for transcellular absorption and specific-targeted delivery of macromolecules to the tissue of interest. Current research suggests that chitosan-based nanoparticles can deliver therapeutic peptide for the treatment of several medical conditions such as diabetes, bacterial infection and cancer. This review summarises the role of chitosan in oral nanoparticle delivery and identifies the clinical application of peptide-loaded chitosan-based nanoparticles.

  20. Self-Assembled Lipid Nanoparticles for Oral Delivery of Heparin-Coated Iron Oxide Nanoparticles for Theranostic Purposes.

    Science.gov (United States)

    Truzzi, Eleonora; Bongio, Chiara; Sacchetti, Francesca; Maretti, Eleonora; Montanari, Monica; Iannuccelli, Valentina; Vismara, Elena; Leo, Eliana

    2017-06-09

    Recently, solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their potential as an oral delivery system, promoting intestinal absorption in the lymphatic circulation which plays a role in disseminating metastatic cancer cells and infectious agents throughout the body. SLN features can be exploited for the oral delivery of theranostics. Therefore, the aim of this work was to design and characterise self-assembled lipid nanoparticles (SALNs) to encapsulate and stabilise iron oxide nanoparticles non-covalently coated with heparin (Fe@hepa) as a model of a theranostic tool. SALNs were characterised for physico-chemical properties (particle size, surface charge, encapsulation efficiency, in vitro stability, and heparin leakage), as well as in vitro cytotoxicity by methyl thiazole tetrazolium (MTT) assay and cell internalisation in CaCo-2, a cell line model used as an indirect indication of intestinal lymphatic absorption. SALNs of about 180 nm, which are stable in suspension and have a high encapsulation efficiency (>90%) were obtained. SALNs were able to stabilise the heparin coating of Fe@hepa, which are typically unstable in physiological environments. Moreover, SALNs-Fe@hepa showed no cytotoxicity, although their ability to be internalised into CaCo-2 cells was highlighted by confocal microscopy analysis. Therefore, the results indicated that SALNs can be considered as a promising tool to orally deliver theranostic Fe@hepa into the lymphatic circulation, although further in vivo studies are needed to comprehend further potential applications.

  1. Global oral health inequalities: task group--implementation and delivery of oral health strategies

    DEFF Research Database (Denmark)

    Sheiham, A; Alexander, D; Cohen, L

    2011-01-01

    This paper reviews the shortcomings of present approaches to reduce oral diseases and inequalities, details the importance of social determinants, and links that to research needs and policies on implementation of strategies to reduce oral health inequalities. Inequalities in health...... their environment. There is a dearth of oral health research on social determinants that cause health-compromising behaviors and on risk factors common to some chronic diseases. The gap between what is known and implemented by other health disciplines and the dental fraternity needs addressing. To re-orient oral...... strategies tailored to determinants and needs of each group along the social gradient. Approaches focusing mainly on downstream lifestyle and behavioral factors have limited success in reducing health inequalities. They fail to address social determinants, for changing people's behaviors requires changing...

  2. Bacteriophage and their potential roles in the human oral cavity

    Directory of Open Access Journals (Sweden)

    Anna Edlund

    2015-04-01

    Full Text Available The human oral cavity provides the perfect portal of entry for viruses and bacteria in the environment to access new hosts. Hence, the oral cavity is one of the most densely populated habitats of the human body containing some 6 billion bacteria and potentially 35 times that many viruses. The role of these viral communities remains unclear; however, many are bacteriophage that may have active roles in shaping the ecology of oral bacterial communities. Other implications for the presence of such vast oral phage communities include accelerating the molecular diversity of their bacterial hosts as both host and phage mutate to gain evolutionary advantages. Additional roles include the acquisitions of new gene functions through lysogenic conversions that may provide selective advantages to host bacteria in response to antibiotics or other types of disturbances, and protection of the human host from invading pathogens by binding to and preventing pathogens from crossing oral mucosal barriers. Recent evidence suggests that phage may be more involved in periodontal diseases than were previously thought, as their compositions in the subgingival crevice in moderate to severe periodontitis are known to be significantly altered. However, it is unclear to what extent they contribute to dysbiosis or the transition of the microbial community into a state promoting oral disease. Bacteriophage communities are distinct in saliva compared to sub- and supragingival areas, suggesting that different oral biogeographic niches have unique phage ecology shaping their bacterial biota. In this review, we summarize what is known about phage communities in the oral cavity, the possible contributions of phage in shaping oral bacterial ecology, and the risks to public health oral phage may pose through their potential to spread antibiotic resistance gene functions to close contacts.

  3. Poly(amido amine) dendrimers as absorption enhancers for oral delivery of camptothecin.

    Science.gov (United States)

    Sadekar, S; Thiagarajan, G; Bartlett, K; Hubbard, D; Ray, A; McGill, L D; Ghandehari, H

    2013-11-01

    Oral delivery of camptothecin has a treatment advantage but is limited by low bioavailability and gastrointestinal toxicity. Poly(amido amine) or PAMAM dendrimers have shown promise as intestinal penetration enhancers, drug solubilizers and drug carriers for oral delivery in vitro and in situ. There have been very limited studies in vivo to evaluate PAMAM dendrimers for oral drug delivery. In this study, camptothecin (5 mg/kg) was formulated and co-delivered with cationic, amine-terminated PAMAM dendrimer generation 4.0 (G4.0) (100 and 300 mg/kg) and anionic, carboxylate-terminated PAMAM generation 3.5 (G3.5) (300 and 1000 mg/kg) in CD-1 mice. Camptothecin associated to a higher extent with G4.0 than G3.5 in the formulation, attributed to an electrostatic interaction on the surface of G4.0. Both PAMAM G4.0 and G3.5 increased camptothecin solubilization in simulated gastric fluid and caused a 2-3 fold increase in oral absorption of camptothecin when delivered at 2 h. PAMAM G4.0 and G3.5 did not increase mannitol transport suggesting that the oral absorption of camptothecin was not due to tight junction modulation. Histologic observations of the epithelial layer of small intestinal segments of the gastrointestinal tract (GIT) at 4 h post dosing supported no evidence of toxicity at the evaluated doses of PAMAM dendrimers. This study demonstrates that both cationic (G.4) and anionic (G3.5) PAMAM dendrimers were effective in enhancing the oral absorption of camptothecin. Results suggest that drug inclusion in PAMAM interior controlled solubilization in simulated gastric and intestinal fluids, and increased oral bioavailability. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Biocompatible nanoemulsions based on hemp oil and less surfactants for oral delivery of baicalein with enhanced bioavailability.

    Science.gov (United States)

    Yin, Juntao; Xiang, Cuiyu; Wang, Peiqing; Yin, Yuyun; Hou, Yantao

    2017-01-01

    Baicalein (BCL) possesses high pharmacological activities but low solubility and stability in the intestinal tract. This study aimed to probe the potential of nanoemulsions (NEs) consisting of hemp oil and less surfactants in ameliorating the oral bioavailability of BCL. BCL-loaded NEs (BCL-NEs) were prepared by high-pressure homogenization technique to reduce the amount of surfactants. BCL-NEs were characterized by particle size, entrapment efficiency (EE), in vitro drug release, and morphology. Bioavailability was studied in Sprague-Dawley rats following oral administration of BCL suspensions, BCL conventional emulsions, and BCL-NEs. The obtained NEs were ~90 nm in particle size with an EE of 99.31%. BCL-NEs significantly enhanced the oral bioavailability of BCL, up to 524.7% and 242.1% relative to the suspensions and conventional emulsions, respectively. BCL-NEs exhibited excellent intestinal permeability and transcellular transport ability. The cytotoxicity of BCL-NEs was documented to be low and acceptable for oral purpose. Our findings suggest that such novel NEs and preparative process provide a promising alternative to current formulation technologies and suitable for oral delivery of drugs with bioavailability issues.

  5. Potential fluoride toxicity from oral medicaments: A review

    OpenAIRE

    Rizwan Ullah; Muhammad Sohail Zafar; Nazish Shahani

    2017-01-01

    The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, tox...

  6. Microencapsulation techniques to develop formulations of insulin for oral delivery: a review.

    Science.gov (United States)

    Cárdenas-Bailón, Fernando; Osorio-Revilla, Guillermo; Gallardo-Velázquez, Tzayhrí

    2013-01-01

    Oral insulin delivery represents one of the most challenging goals for pharmaceutical industry. In general, it is accepted that oral administration of insulin would be more accepted by patients and insulin would be delivered in a more physiological way than the parenteral route. From all strategies to deliverer insulin orally, microencapsulation or nanoencapsulation of insulin are the most promising approaches because these techniques protect insulin from enzymatic degradation in stomach, show a good release profile at intestine pH values, maintain biological activity during formulation and enhance intestinal permeation at certain extent. From different microencapsulation techniques, it seems that complex coacervation, multiple emulsion and internal gelation are the most appropriate techniques to encapsulate insulin due to their relative ease of preparation. Besides that, the use of organic solvents is not required and can be scaled up at low cost; however, relative oral bioavailability still needs to be improved.

  7. Kefiran-alginate gel microspheres for oral delivery of ciprofloxacin.

    Science.gov (United States)

    Blandón, Lina M; Islan, German A; Castro, Guillermo R; Noseda, Miguel D; Thomaz-Soccol, Vanete; Soccol, Carlos R

    2016-09-01

    Ciprofloxacin is a broad-spectrum antibiotic associated with gastric and intestinal side effects after extended oral administration. Alginate is a biopolymer commonly employed in gel synthesis by ionotropic gelation, but unstable in the presence of biological metal-chelating compounds and/or under dried conditions. Kefiran is a microbial biopolymer able to form gels with the advantage of displaying antimicrobial activity. In the present study, kefiran-alginate gel microspheres were developed to encapsulate ciprofloxacin for antimicrobial controlled release and enhanced bactericidal effect against common pathogens. Scanning electron microscopy (SEM) analysis of the hybrid gel microspheres showed a spherical structure with a smoother surface compared to alginate gel matrices. In vitro release of ciprofloxacin from kefiran-alginate microspheres was less than 3.0% and 5.0% at pH 1.2 (stomach), and 5.0% and 25.0% at pH 7.4 (intestine) in 3 and 21h, respectively. Fourier transform infrared spectroscopy (FTIR) of ciprofloxacin-kefiran showed the displacement of typical bands of ciprofloxacin and kefiran, suggesting a cooperative interaction by hydrogen bridges between both molecules. Additionally, the thermal analysis of ciprofloxacin-kefiran showed a protective effect of the biopolymer against ciprofloxacin degradation at high temperatures. Finally, antimicrobial assays of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhymurium, and Staphylococcus aureus demonstrated the synergic effect between ciprofloxacin and kefiran against the tested microorganisms. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Challenges in oral drug delivery in patients with esophageal dysphagia.

    Science.gov (United States)

    Kappelle, Wouter F W; Siersema, Peter D; Bogte, Auke; Vleggaar, Frank P

    2016-01-01

    Esophageal dysphagia is a commonly reported symptom with various benign and malignant causes. Esophageal dysphagia can impede intake of oral medication, which often poses a major challenge for both patients and physicians. The best way to address this challenge depends of the cause of dysphagia. The pathophysiology of esophageal dysphagia is discussed, diagnostic tools to determine its cause are reviewed and recent developments in the treatment of esophageal dysphagia are discussed. Alternative options to administer medication in dysphagia are discussed and the appropriateness of them reviewed. Two ways can be followed to allow medication intake in patients with esophageal dysphagia, i.e. altering medication or resolving dysphagia. The latter is generally preferred, since esophageal dysphagia rarely only impedes medication intake. Esophageal resection is possible in more advanced esophageal cancer stages due to advances in neo-adjuvant therapy. Due to recent improvements in intraluminal radiotherapy, it can be expected that this will be the primary treatment in a palliative setting. Temporary self-expandable metal stent placement is a promising new alternative for bougienage in difficult-to-treat benign strictures.

  9. NMR characterisation and transdermal drug delivery potential of microemulsion systems

    DEFF Research Database (Denmark)

    Kreilgaard, Mads; Pedersen, E J; Jaroszewski, J W

    2000-01-01

    The purpose of this study was to investigate the influence of structure and composition of microemulsions (Labrasol/Plurol Isostearique/isostearylic isostearate/water) on their transdermal delivery potential of a lipophilic (lidocaine) and a hydrophilic model drug (prilocaine hydrochloride), and ...

  10. Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery

    Directory of Open Access Journals (Sweden)

    Chen CH

    2015-03-01

    Full Text Available Chun-Han Chen,1,2 Cheng-Chih Chang,1 Tsung-Hsien Shih,2 Ibrahim A Aljuffali,3 Ta-Sen Yeh,4,5 Jia-You Fang6–8 1Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan; 3Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 4Department of Surgery, Chang Gung Memorial Hospital, 5School of Medicine, College of Medicine, 6Pharmaceutics Laboratory, Graduate Institute of Natural Products, 7Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, 8Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan Abstract: Roux-en-Y gastric bypass (RYGB is a popular surgery to reduce the body weight of obese patients. Although food intake is restricted by RYGB, drug absorption is also decreased. The purpose of this study was to develop novel self-nanoemulsifying drug delivery systems (SNEDDS for enhancing the oral delivery of silymarin, which has poor water solubility. The SNEDDS were characterized by size, zeta potential, droplet number, and morphology. A technique of RYGB was performed in Sprague-Dawley rats. SNEDDS were administered at a silymarin dose of 600 mg/kg in normal and RYGB rats for comparison with silymarin aqueous suspension and polyethylene glycol (PEG 400 solution. Plasma silibinin, the main active ingredient in silymarin, was chosen for estimating the pharmacokinetic parameters. SNEDDS diluted in simulated gastric fluid exhibited a droplet size of 190 nm with a spherical shape. The nanocarriers promoted silibinin availability via oral ingestion in RYGB rats by 2.5-fold and 1.5-fold compared to the suspension and PEG 400 solution, respectively. A significant double-peak concentration of silibinin was detected for RYGB rats receiving SNEDDS. Fluorescence

  11. Oral delivery of human biopharmaceuticals, autoantigens and vaccine antigens bioencapsulated in plant cells.

    Science.gov (United States)

    Kwon, Kwang-Chul; Verma, Dheeraj; Singh, Nameirakpam D; Herzog, Roland; Daniell, Henry

    2013-06-15

    Among 12billion injections administered annually, unsafe delivery leads to >20million infections and >100million reactions. In an emerging new concept, freeze-dried plant cells (lettuce) expressing vaccine antigens/biopharmaceuticals are protected in the stomach from acids/enzymes but are released to the immune or blood circulatory system when plant cell walls are digested by microbes that colonize the gut. Vaccine antigens bioencapsulated in plant cells upon oral delivery after priming, conferred both mucosal and systemic immunity and protection against bacterial, viral or protozoan pathogens or toxin challenge. Oral delivery of autoantigens was effective against complications of type 1 diabetes and hemophilia, by developing tolerance. Oral delivery of proinsulin or exendin-4 expressed in plant cells regulated blood glucose levels similar to injections. Therefore, this new platform offers a low cost alternative to deliver different therapeutic proteins to combat infectious or inherited diseases by eliminating inactivated pathogens, expensive purification, cold storage/transportation and sterile injections. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Microparticles, microcapsules and microspheres: A review of recent developments and prospects for oral delivery of insulin.

    Science.gov (United States)

    Wong, Chun Y; Al-Salami, Hani; Dass, Crispin R

    2018-02-15

    Diabetes mellitus is a chronic metabolic health disease affecting the homeostasis of blood sugar levels. However, subcutaneous injection of insulin can lead to patient non-compliance, discomfort, pain and local infection. Sub-micron sized drug delivery systems have gained attention in oral delivery of insulin for diabetes treatment. In most of the recent literature, the terms "microparticles" and "nanoparticle" refer to particles where the dimensions of the particle are measured in micrometers and nanometers respectively. For instance, insulin-loaded particles are defined as microparticles with size larger than 1 μm by most of the research groups. The size difference between nanoparticles and microparticles proffers numerous effects on the drug loading efficiency, aggregation, permeability across the biological membranes, cell entry and tissue retention. For instance, microparticulate drug delivery systems have demonstrated a number of advantages including protective effect against enzymatic degradation, enhancement of peptide stability, site-specific and controlled drug release. Compared to nanoparticulate drug delivery systems, microparticulate formulations can facilitate oral absorption of insulin by paracellular, transcellular and lymphatic routes. In this article, we review the current status of microparticles, microcapsules and microspheres for oral administration of insulin. A number of novel techniques including layer-by-layer coating, self-polymerisation of shell, nanocomposite microparticulate drug delivery system seem to be promising for enhancing the oral bioavailability of insulin. This review draws several conclusions for future directions and challenges to be addressed for optimising the properties of microparticulate drug formulations and enhancing their hypoglycaemic effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Chitosan/o-carboxymethyl chitosan nanoparticles for efficient and safe oral anticancer drug delivery: in vitro and in vivo evaluation.

    Science.gov (United States)

    Feng, Chao; Wang, Zhiguo; Jiang, Changqing; Kong, Ming; Zhou, Xuan; Li, Yang; Cheng, Xiaojie; Chen, Xiguang

    2013-11-30

    The present study investigated the ability of a polyelectrolyte complex (CS/CMCS-NPs), composed of chitosan (CS) and o-carboxymeymethy chitosan (CMCS) as a pH responsive carrier for oral delivery of doxorubicin hydrochloride (DOX). The obtained CS/CMCS-NPs were characterized for various parameters including morphology, particle size, zeta potential, entrapment efficiency and stability under the simulated GI tract conditions. The pH responsive stability of the DOX-loaded CS/CMCS nanoparticles (DOX:CS/CMCS-NPs) determined the drug release rate, which was lower in acidic pH than the neutral. Ex vivo intestinal adhesion and permeation indicated DOX:CS/CMCS-NGs were able to enhance absorption of DOX throughout the entire small intestine, especially in jejunum and ileum. Oral administration of DOX:CS/CMCS-NPs was effective to deliver DOX into blood, giving an absolute bioavailability of 42%. The tissue distribution and toxicity of DOX:CS/CMCS-NPs in rats showed low level of DOX in heart and kidney, and obviously decreased cardiac and renal toxicities. These results indicated CS/CMCS-NPs were highly efficient and safe as an oral delivery system for DOX. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Challenges in the local delivery of peptides and proteins for oral mucositis management.

    Science.gov (United States)

    Campos, João C; Cunha, João D; Ferreira, Domingos C; Reis, Salette; Costa, Paulo J

    2018-04-24

    Oral mucositis, a common inflammatory side effect of oncological treatments, is a disorder of the oral mucosa that can cause painful ulcerations, local motor disabilities, and an increased risk of infections. Due to the discomfort it produces and the associated health risks, it can lead to cancer treatment restrains, such as the need for dose reduction, cycle delays or abandonment. Current mucositis management has low efficiency in prevention and treatment. A topical drug application for a local action can be a more effective approach than systemic routes when addressing oral cavity pathologies. Local delivery of growth factors, antibodies, and anti-inflammatory cytokines have shown promising results. However, due to the peptide and protein nature of these novel agents, and the several anatomic, physiological and environmental challenges of the oral cavity, their local action might be limited when using traditional delivering systems. This review is an awareness of the issues and strategies in the local delivery of macromolecules for the management of oral mucositis. Copyright © 2018. Published by Elsevier B.V.

  15. Probiotic Ferulic Acid Esterase Active Lactobacillus fermentum NCIMB 5221 APA Microcapsules for Oral Delivery: Preparation and in Vitro Characterization

    Directory of Open Access Journals (Sweden)

    Catherine Tomaro-Duchesneau

    2012-02-01

    Full Text Available Probiotics possess potential therapeutic and preventative effects for various diseases and metabolic disorders. One important limitation for the oral delivery of probiotics is the harsh conditions of the upper gastrointestinal tract (GIT which challenge bacterial viability and activity. One proposed method to surpass this obstacle is the use of microencapsulation to improve the delivery of bacterial cells to the lower GIT. The aim of this study is to use alginate-poly-L-lysine-alginate (APA microcapsules to encapsulate Lactobacillus fermentum NCIMB 5221 and characterize its enzymatic activity and viability through a simulated GIT. This specific strain, in previous research, was characterized for its inherent ferulic acid esterase (FAE activity which could prove beneficial in the development of a therapeutic for the treatment and prevention of cancers and metabolic disorders. Our findings demonstrate that the APA microcapsule does not slow the mass transfer of substrate into and that of the FA product out of the microcapsule, while also not impairing bacterial cell viability. The use of simulated gastrointestinal conditions led to a significant 2.5 log difference in viability between the free (1.10 × 104 ± 1.00 × 103 cfu/mL and the microencapsulated (5.50 × 106 ± 1.00 × 105 cfu/mL L. fermentum NCIMB 5221 following exposure. The work presented here suggests that APA microencapsulation can be used as an effective oral delivery method for L. fermentum NCIMB 5221, a FAE-active probiotic strain.

  16. Probiotic Ferulic Acid Esterase Active Lactobacillus fermentum NCIMB 5221 APA Microcapsules for Oral Delivery: Preparation and in Vitro Characterization

    Science.gov (United States)

    Tomaro-Duchesneau, Catherine; Saha, Shyamali; Malhotra, Meenakshi; Coussa-Charley, Michael; Kahouli, Imen; Jones, Mitchell L.; Labbé, Alain; Prakash, Satya

    2012-01-01

    Probiotics possess potential therapeutic and preventative effects for various diseases and metabolic disorders. One important limitation for the oral delivery of probiotics is the harsh conditions of the upper gastrointestinal tract (GIT) which challenge bacterial viability and activity. One proposed method to surpass this obstacle is the use of microencapsulation to improve the delivery of bacterial cells to the lower GIT. The aim of this study is to use alginate-poly-L-lysine-alginate (APA) microcapsules to encapsulate Lactobacillus fermentum NCIMB 5221 and characterize its enzymatic activity and viability through a simulated GIT. This specific strain, in previous research, was characterized for its inherent ferulic acid esterase (FAE) activity which could prove beneficial in the development of a therapeutic for the treatment and prevention of cancers and metabolic disorders. Our findings demonstrate that the APA microcapsule does not slow the mass transfer of substrate into and that of the FA product out of the microcapsule, while also not impairing bacterial cell viability. The use of simulated gastrointestinal conditions led to a significant 2.5 log difference in viability between the free (1.10 × 104 ± 1.00 × 103 cfu/mL) and the microencapsulated (5.50 × 106 ± 1.00 × 105 cfu/mL) L. fermentum NCIMB 5221 following exposure. The work presented here suggests that APA microencapsulation can be used as an effective oral delivery method for L. fermentum NCIMB 5221, a FAE-active probiotic strain. PMID:24288090

  17. Probiotic Ferulic Acid Esterase Active Lactobacillus fermentum NCIMB 5221 APA Microcapsules for Oral Delivery: Preparation and in Vitro Characterization.

    Science.gov (United States)

    Tomaro-Duchesneau, Catherine; Saha, Shyamali; Malhotra, Meenakshi; Coussa-Charley, Michael; Kahouli, Imen; Jones, Mitchell L; Labbé, Alain; Prakash, Satya

    2012-02-16

    Probiotics possess potential therapeutic and preventative effects for various diseases and metabolic disorders. One important limitation for the oral delivery of probiotics is the harsh conditions of the upper gastrointestinal tract (GIT) which challenge bacterial viability and activity. One proposed method to surpass this obstacle is the use of microencapsulation to improve the delivery of bacterial cells to the lower GIT. The aim of this study is to use alginate-poly-L-lysine-alginate (APA) microcapsules to encapsulate Lactobacillus fermentum NCIMB 5221 and characterize its enzymatic activity and viability through a simulated GIT. This specific strain, in previous research, was characterized for its inherent ferulic acid esterase (FAE) activity which could prove beneficial in the development of a therapeutic for the treatment and prevention of cancers and metabolic disorders. Our findings demonstrate that the APA microcapsule does not slow the mass transfer of substrate into and that of the FA product out of the microcapsule, while also not impairing bacterial cell viability. The use of simulated gastrointestinal conditions led to a significant 2.5 log difference in viability between the free (1.10 × 104 ± 1.00 × 103 cfu/mL) and the microencapsulated (5.50 × 106 ± 1.00 × 105 cfu/mL) L. fermentum NCIMB 5221 following exposure. The work presented here suggests that APA microencapsulation can be used as an effective oral delivery method for L. fermentum NCIMB 5221, a FAE-active probiotic strain.

  18. Evaluation of critical formulation parameters in design and differentiation of self-microemulsifying drug delivery systems (SMEDDSs) for oral delivery of aciclovir.

    Science.gov (United States)

    Janković, Jovana; Djekic, Ljiljana; Dobričić, Vladimir; Primorac, Marija

    2016-01-30

    The study investigated the influence of formulation parameters for design of self-microemulsifying drug delivery systems (SMEDDSs) comprising oil (medium chain triglycerides) (10%), surfactant (Labrasol(®), polysorbate 20, or Kolliphor(®) RH40), cosurfactant (Plurol(®) Oleique CC 497) (q.s. ad 100%), and cosolvent (glycerol or macrogol 400) (20% or 30%), and evaluate their potential as carriers for oral delivery of a poorly permeable antivirotic aciclovir (acyclovir). The drug loading capacity of the prepared formulations ranged from 0.18-31.66 mg/ml. Among a total of 60 formulations, three formulations meet the limits for average droplet size (Z-ave) and polydispersity index (PdI) that have been set for SMEDDSs (Z-ave≤100nm, PdI<0.250) upon spontaneous dispersion in 0.1M HCl and phosphate buffer pH 7.2. SMEDDSs with the highest aciclovir loading capacity (24.06 mg/ml and 21.12 mg/ml) provided the in vitro drug release rates of 0.325 mg cm(-2)min(-1) and 0.323 mg cm(-2)min(-1), respectively, and significantly enhanced drug permeability in the parallel artificial membrane permeability assay (PAMPA), in comparison with the pure drug substance. The results revealed that development of SMEDDSs with enhanced drug loading capacity and oral delivery potential, required optimization of hydrophilic ingredients, in terms of size of hydrophilic moiety of the surfactant, surfactant-to-cosurfactant mass ratio (Km), and log P of the cosolvent. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Peptide-based soft materials as potential drug delivery vehicles.

    Science.gov (United States)

    Verma, Sandeep; Joshi, K B; Ghosh, Surajit

    2007-11-01

    Emerging concepts in the construction of nanostructures hold immense potential in the areas of drug delivery and targeting. Such nanoscopic assemblies/structures, similar to natural proteins and self-associating systems, may lead to the formation of programmable soft structures with expanded drug delivery options and the capability to circumvent first-pass metabolism. This article aims to illustrate key recent developments and innovative bioinspired design paradigms pertaining to peptide-containing self-assembled tubular and vesicular soft structures. Soft structures are composed of components that self-assemble to reveal diverse morphologies stabilized by weak, noncovalent interactions. Morphological properties of such structures and their ability to encapsulate drugs, biologicals and bioactive small molecules, with the promise of targeted delivery, are discussed.

  20. Self-double-emulsifying drug delivery system (SDEDDS): a new way for oral delivery of drugs with high solubility and low permeability.

    Science.gov (United States)

    Qi, Xiaole; Wang, Lishuang; Zhu, Jiabi; Hu, Zhenyi; Zhang, Jie

    2011-05-16

    Water-in-oil-in-water (w/o/w) double emulsions are potential for enhancing oral bioavailability of drugs with high solubility and low permeability, but their industrial application is limited due to the instability. Herein, we developed a novel formulation, self-double-emulsifying drug delivery systems (SDEDDS) by formulating mixtures of hydrophilic surfactants and water-in-oil (w/o) emulsions, which were easier to be stable through formulations optimization. SDEDDS can spontaneously emulsify to water-in-oil-in-water (w/o/w) double emulsions in the mixed aqueous gastrointestinal environment, with drugs encapsulated in the internal water phase of the double emulsions. We employed SDEDDS to improve the oral absorption of pidotimod, a peptide-like drug with high solubility and low permeability. The optimized pidotimod-SDEDDS were found to be stable up to 6 months under 25°C. Plasma concentration-time profiles from pharmacokinetic studies in rats dosed with SDEDDS showed 2.56-fold (p<0.05) increased absorption of pidotimod, compared to the pidotimod solution. Histopathologic studies confirmed that SDEDDS exerted absorption promoting effect without serious local damages. These studies demonstrate that SDEDDS may be a promising strategy for peroral delivery of peptide and peptidomimetic drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. The potential of dental-protective chewing gum in oral health interventions.

    Science.gov (United States)

    Ly, Kiet A; Milgrom, Peter; Rothen, Marilynn

    2008-05-01

    The authors provide an overview of chewing gum as a delivery vehicle for dental-protective agents, highlighting xylitol and its potential application in caries-prevention programs for children. The authors reviewed selected clinical investigations and previous reviews associated with chewing gum containing substances such as calcium, bicarbonate, carbamide, chlorhexidine, fluoride and xylitol and their effects on reducing caries. They searched the MEDLINE database by using the key words "dental caries," "oral health," "calcium," "bicarbonate," "carbamide," "chlorhexidine," "fluoride" and "xylitol." Chewing gum is being used as a delivery vehicle for substances such as calcium, bicarbonate, carbamide, chlorhexidine, fluoride and xylitol to improve oral health and reduce caries. These substances exhibit properties that are protective of the oral environment and mediate common oral diseases. The debate for advocating xylitol use in caries prevention is advancing; however, chewing gum use by young schoolchildren in the United States is hindered by choking hazard concerns and lack of specific xylitol dosing recommendations. The use of chewing gum containing dental-protective substances, particularly xylitol, in caries-prevention programs can reduce the tooth decay epidemic. Chewing gum use by children in the school setting should be reconsidered.

  2. Hot embossing and mechanical punching of biodegradable microcontainers for oral drug delivery

    DEFF Research Database (Denmark)

    Petersen, Ritika Singh; Mahshid, Rasoul; Andersen, Nis Korsgaard

    2015-01-01

    A process has been developed to fabricate discrete three-dimensional microcontainers for oral drug delivery application in Poly-L-Lactic Acid (PLLA) polymer. The method combines hot embossing for the definition of holes in a PLLA film and mechanical punching to penetrate the polymer layer around...... and shapes of microcontainers. Finally, the process is compatible with roll-to-roll processing that could lead to low cost high volume production. © 2014 Elsevier B.V. All rights reserved....

  3. Polymeric particulate technologies for oral drug delivery and targeting: A pathophysiological perspective

    DEFF Research Database (Denmark)

    Hunter, A. Christy; Elsom, Jacqueline; Wibroe, Peter Popp

    2012-01-01

    Publication year: 2012 Source:Maturitas, Volume 73, Issue 1 A. Christy Hunter, Jacqueline Elsom, Peter P. Wibroe, S. Moein Moghimi The oral route for delivery of pharmaceuticals is the most widely used and accepted. Nanoparticles and microparticles are increasingly being applied within this arena....... It is the purpose of this review to describe these cutting edge technologies and specifically focus on the interaction and fate of these polymers within the gastrointestinal system....

  4. Self-Micro Emulsifying Drug Delivery Systems: a Strategy to Improve Oral Bioavailability

    Directory of Open Access Journals (Sweden)

    Vijay K. Sharma

    Full Text Available Aim: Oral route has always been the favorite route of drug administration in many diseases and till today it is the first way investigated in the development of new dosage forms. The major problem in oral drug formulations is low and erratic bioavailability, which mainly results from poor aqueous solubility, thereby pose problems in their formulation. For the therapeutic delivery of lipophilic active moieties (BCS class II drugs, lipid based formulations are inviting increasing attention. Methods: To that aim, from the web sites of PubMed, HCAplus, Thomson, and Registry were used as the main sources to perform the search for the most significant research articles published on the subject. The information was then carefully analyzed, highlighting the most important results in the formulation and development of self-micro emulsifying drug delivery systems as well as its therapeutic activity. Results: Self-emulsifying drug delivery system (SMEDDS has gained more attention due to enhanced oral bio-availability enabling reduction in dose, more consistent temporal profiles of drug absorption, selective targeting of drug(s toward specific absorption window in GIT, and protection of drug(s from the unreceptive environment in gut. Conclusions: This article gives a complete overview of SMEDDS as a promising approach to effectively deal with the problem of poorly soluble molecules.

  5. Stabilization challenges and formulation strategies associated with oral biologic drug delivery systems.

    Science.gov (United States)

    Truong-Le, Vu; Lovalenti, Phillip M; Abdul-Fattah, Ahmad M

    2015-10-01

    Delivery of proteins to mucosal tissues of GI tract typically utilize formulations which protect against proteolysis and target the mucosal tissues. Using case studies from literature and the authors' own work, the in-process stability and solid state storage stability of biopharmaceuticals formulated in delivery systems designed for oral delivery to the GI tract will be reviewed. Among the range of delivery systems, biodegradable polymer systems for protection and controlled release of proteins have been the most studied; hence these systems will be covered in greater depth. These delivery systems include polymeric biodegradable microspheres or nanospheres that contain proteins or vaccines, which are designed to reduce the number of administrations/inoculations and the total protein dose required to achieve the desired biological effect. Specifically, this review will include a landscape survey of the systems that have been studied, the manufacturing processes involved, stability through the manufacturing process, key pharmaceutical formulation parameters that impact stability of the encased proteins, and storage stability of the encapsulated proteins in these delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Orally active-targeted drug delivery systems for proteins and peptides.

    Science.gov (United States)

    Li, Xiuying; Yu, Miaorong; Fan, Weiwei; Gan, Yong; Hovgaard, Lars; Yang, Mingshi

    2014-09-01

    In the past decade, extensive efforts have been devoted to designing 'active targeted' drug delivery systems (ATDDS) to improve oral absorption of proteins and peptides. Such ATDDS enhance cellular internalization and permeability of proteins and peptides via molecular recognition processes such as ligand-receptor or antigen-antibody interaction, and thus enhance drug absorption. This review focuses on recent advances with orally ATDDS, including ligand-protein conjugates, recombinant ligand-protein fusion proteins and ligand-modified carriers. In addition to traditional intestinal active transport systems of substrates and their corresponding receptors, transporters and carriers, new targets such as intercellular adhesion molecule-1 and β-integrin are also discussed. ATDDS can improve oral absorption of proteins and peptides. However, currently, no clinical studies on ATDDS for proteins and peptides are underway, perhaps due to the complexity and limited knowledge of transport mechanisms. Therefore, more research is warranted to optimize ATDDS efficiency.

  7. Microfluidic conceived Trojan microcarriers for oral delivery of nanoparticles.

    Science.gov (United States)

    Khan, Ikram Ullah; Serra, Christophe A; Anton, Nicolas; Er-Rafik, Mériem; Blanck, C; Schmutz, Marc; Kraus, Isabelle; Messaddeq, Nadia; Sutter, Christophe; Anton, Halina; Klymchenko, Andrey S; Vandamme, Thierry F

    2015-09-30

    In this study, we report on a novel method for the synthesis of poly(acrylamide) Trojan microparticles containing ketoprofen loaded poly(ethyl acrylate) or poly(methyl acrylate) nanoparticles. To develop these composite particles, a polymerizable nanoemulsion was used as a template. This nanoemulsion was obtained in an elongational-flow micromixer (μRMX) which was linked to a capillary-based microfluidic device for its emulsification into micron range droplets. Downstream, the microdroplets were hardened into Trojan particles in the size range of 213-308 μm by UV initiated free radical polymerization. The nanoemulsion size varied from 98 -132 nm upon changes in surfactant concentration and number of operating cycles in μRMX. SEM and confocal microscopy confirmed the Trojan morphology. Under SEM it was observed that the polymerization reduced the size of the nanoemulsion down to 20-32 nm for poly(ethyl acrylate) and 10-15 nm for poly(methyl acrylate) nanoparticles. This shrinkage was confirmed by cryo-TEM studies. We further showed that Trojan microparticles released embedded nanoparticles on contact with suitable media as confirmed by transmission electron microscopy. In a USP phosphate buffer solution of pH 6.8, Trojan microparticles containing poly(ethyl acrylate) nanoparticles released 35% of encapsulated ketoprofen over 24h. The low release of the drug was attributed to the overall low concentration of nanoparticles and attachment of some of nanoparticles to the poly(acrylamide) matrix. Thus, this novel method has shown possibility to develop Trojan particles convieniently with potential to deliver nanoparticles in the gastrointestinal tract. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Yeast Microcapsule-Mediated Targeted Delivery of Diverse Nanoparticles for Imaging and Therapy via the Oral Route.

    Science.gov (United States)

    Zhou, Xing; Zhang, Xiangjun; Han, Songling; Dou, Yin; Liu, Mengyu; Zhang, Lin; Guo, Jiawei; Shi, Qing; Gong, Genghao; Wang, Ruibing; Hu, Jiang; Li, Xiaohui; Zhang, Jianxiang

    2017-02-08

    Targeting of nanoparticles to distant diseased sites after oral delivery remains highly challenging due to the existence of many biological barriers in the gastrointestinal tract. Here we report targeted oral delivery of diverse nanoparticles in multiple disease models, via a "Trojan horse" strategy based on a bioinspired yeast capsule (YC). Diverse charged nanoprobes including quantum dots (QDs), iron oxide nanoparticles (IONPs), and assembled organic fluorescent nanoparticles can be effectively loaded into YC through electrostatic force-driven spontaneous deposition, resulting in different diagnostic YC assemblies. Also, different positive nanotherapies containing an anti-inflammatory drug indomethacin (IND) or an antitumor drug paclitaxel (PTX) are efficiently packaged into YC. YCs containing either nanoprobes or nanotherapies may be rapidly endocytosed by macrophages and maintained in cells for a relatively long period of time. Post oral administration, nanoparticles packaged in YC are first transcytosed by M cells and sequentially endocytosed by macrophages, then transported to neighboring lymphoid tissues, and finally delivered to remote diseased sites of inflammation or tumor in mice or rats, all through the natural route of macrophage activation, recruitment, and deployment. For the examined acute inflammation model, the targeting efficiency of YC-delivered QDs or IONPs is even higher than that of control nanoprobes administered at the same dose via intravenous injection. Assembled IND or PTX nanotherapies orally delivered via YCs exhibit remarkably potentiated efficacies as compared to nanotherapies alone in animal models of inflammation and tumor, which is consistent with the targeting effect and enhanced accumulation of drug molecules at diseased sites. Consequently, through the intricate transportation route, nanoprobes or nanotherapies enveloped in YC can be preferentially delivered to desired targets, affording remarkably improved efficacies for the

  9. Enhanced oral bioavailability and sustained delivery of glimepiride via niosomal encapsulation: in-vitro characterization and in-vivo evaluation.

    Science.gov (United States)

    Mohsen, Amira Mohamed; AbouSamra, Mona Mahmoud; ElShebiney, Shaimaa Ahmed

    2017-08-01

    This study was designed to investigate the potency of niosomes, for glimepiride (GLM) encapsulation, aiming at enhancing its oral bioavailability and hypoglycemic efficacy. Niosomes containing nonionic surfactants (NIS) were prepared by thin film hydration technique and characterized. In-vitro release study was performed using a dialysis technique. In-vivo pharmacodynamic studies, as well as pharmacokinetic evaluation were performed on alloxan-induced diabetic rats. GLM niosomes exhibited high-entrapment efficiency percentages (E.E. %) up to 98.70% and a particle size diameter ranging from 186.8 ± 18.69 to 797.7 ± 12.45 nm, with negatively charged zeta potential (ZP). Different GLM niosomal formulation showed retarded in vitro release, compared to free drug. In-vivo studies revealed the superiority of GLM niosomes in lowering blood glucose level (BGL) and in maintaining a therapeutic level of GLM for a longer period of time, as compared to free drug and market product. There was no significant difference between mean plasma AUC 0-48 hr of GLM-loaded niosomes and that of market product. GLM-loaded niosomes exhibited seven-fold enhancement in relative bioavailability in comparison with free drug. These findings reinforce the potential use of niosomes for enhancing the oral bioavailability and prolonged delivery of GLM via oral administration.

  10. Formulation of avanafil in a solid self-nanoemulsifying drug delivery system for enhanced oral delivery.

    Science.gov (United States)

    Soliman, Kareem AbuBakr; Ibrahim, Howida Kamal; Ghorab, Mahmoud Mohammed

    2016-10-10

    Avanafil was incorporated into solid self-nanoemulsifying systems with the aim of improving its oral bioavailability. Labrafil, Labrafac, and Miglyol 812 N were investigated as oils, Tween 80 and Cremophor EL as surfactants, and Transcutol HP as a co-surfactant. Nine formulations produced clear solutions of 13.89-38.09nm globules after aqueous dilution. Adsorption of preconcentrate onto Aeroperl 300 Pharma at a 2:1 ratio had no effect on nanoemulsion particle size. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy indicated that avanafil was molecularly dispersed within the solid nanosystems. A formulation containing 10% Labrafil, 60% Tween 80, and 30% Transcutol HP had the highest drug loading (44.48mg/g) and an acceptable in vitro dissolution profile (96.42% within 30min). This formulation was chemically and physically stable for 6months under accelerated storage conditions and it produced a 3.2-fold increase in bioavailability in rabbits, as compared to conventional commercially available avanafil tablets (Spedra(®)). Copyright © 2016 Elsevier B.V. All rights reserved.

  11. A review of advanced oral drug delivery technologies facilitating the protection and absorption of protein and peptide molecules.

    Science.gov (United States)

    Choonara, Bibi F; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Pillay, Viness

    2014-11-15

    The oral delivery of proteins and peptides is a dynamic research field despite the numerous challenges limiting their effective delivery. Successful oral delivery of proteins and peptides requires the accomplishment of three key tasks: protection of the macromolecules from degradation in the gastrointestinal tract (GIT), permeation through the intestinal barrier and absorption of molecules into the systemic circulation. Currently, no clinically useful oral formulations have been developed but several attempts have been made to overcome the challenges of low oral bioavailability resulting from poor absorption, poor permeation and enzymatic degradation of the proteins and peptides in the GIT. Present strategies attempt to provide structural protection of the proteins and peptides and improved absorption through the use of enzyme inhibitors, absorption enhancers, novel polymeric delivery systems and chemical modification. However, each of these technologies has their limitations despite showing positive results. This review attempts to discuss the physical and chemical barriers of the GIT with particular emphasis on the current approaches employed to overcome these barriers, including the evaluation of other non-parenteral routes of protein and peptide delivery. In addition, this review assimilates oral formulation strategies under development and within the clinical trial stage in relation to their benefits and drawbacks with regard to facilitating optimal protection and absorption of proteins and peptides, as well as pertinent future challenges and opportunities governing oral drug delivery. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Enhancement of oral bioavailability of cyclosporine A: comparison of various nanoscale drug-delivery systems

    Directory of Open Access Journals (Sweden)

    Wang K

    2014-10-01

    Full Text Available Kai Wang,1–3 Jianping Qi,1 Tengfei Weng,1,2 Zhiqiang Tian,1 Yi Lu,1 Kaili Hu,4 Zongning Yin,2 Wei Wu1 1School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai, People’s Republic of China; 2West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Tropical Crops Genetic Resources Institute, Hainan Provincial Engineering Research Center for Blumea Balsamifera, Chinese Academy of Tropical Agricultural Sciences, Danzhou, Hainan, People’s Republic of China; 4Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaAbstract: A variety of nanoscale delivery systems have been shown to enhance the oral absorption of poorly water-soluble and poorly permeable drugs. However, the performance of these systems has seldom been evaluated simultaneously. The aim of this study was to compare the bioavailability enhancement effect of lipid-based nanocarriers with poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs to highlight the importance of the lipid composition, with cyclosporine A (CyA as a model drug. CyA-loaded PLGA NPs, nanostructured lipid carriers (NLCs, and self-microemulsifying drug-delivery systems (SMEDDS were prepared. The particle size of PLGA NPs (182.2±12.8 nm was larger than that of NLCs (89.7±9.0 nm and SMEDDS (26.9±1.9 nm. All vehicles are charged negatively. The entrapment efficiency of PLGA NPs and NLCs was 87.6%±1.6% and 80.3%±0.6%, respectively. In vitro release tests indicated that the cumulative release of CyA was lower than 4% from all vehicles, including Sandimmun Neoral®, according to the dialysis method. Both NLCs and SMEDDS showed high relative oral bioavailability, 111.8% and 73.6%, respectively, after oral gavage administration to beagle dogs, which was not statistically different from commercial Sandimmun Neoral®. However, PLGA NPs

  13. Biocompatible nanoemulsions based on hemp oil and less surfactants for oral delivery of baicalein with enhanced bioavailability

    Directory of Open Access Journals (Sweden)

    Yin J

    2017-04-01

    Full Text Available Juntao Yin,1,* Cuiyu Xiang,1,* Peiqing Wang,1 Yuyun Yin,2 Yantao Hou3 1Department of Pharmaceutics, Huaihe Hospital Affiliated to Henan University, Kaifeng, 2Department of Physiochemical Analysis, Henan Provincial Institute for Food and Drug Control, Zhengzhou, 3Department of Pharmaceutical Engineering, Henan Vocational College of Applied Technology, Kaifeng, People’s Republic of China *These authors contributed equally to this work Abstract: Baicalein (BCL possesses high pharmacological activities but low solubility and stability in the intestinal tract. This study aimed to probe the potential of nanoemulsions (NEs consisting of hemp oil and less surfactants in ameliorating the oral bioavailability of BCL. BCL-loaded NEs (BCL-NEs were prepared by high-pressure homogenization technique to reduce the amount of surfactants. BCL-NEs were characterized by particle size, entrapment efficiency (EE, in vitro drug release, and morphology. Bioavailability was studied in Sprague-Dawley rats following oral administration of BCL suspensions, BCL conventional emulsions, and BCL-NEs. The obtained NEs were ~90 nm in particle size with an EE of 99.31%. BCL-NEs significantly enhanced the oral bioavailability of BCL, up to 524.7% and 242.1% relative to the suspensions and conventional emulsions, respectively. BCL-NEs exhibited excellent intestinal permeability and transcellular transport ability. The cytotoxicity of BCL-NEs was documented to be low and acceptable for oral purpose. Our findings suggest that such novel NEs and preparative process provide a promising alternative to current formulation technologies and suitable for oral delivery of drugs with bioavailability issues. Keywords: baicalein, nanoemulsions, biocompatibility, high-pressure homogenization, hemp oil, bioavailability

  14. Development and evaluation of mucoadhesive nanoparticles based on thiolated Eudragit for oral delivery of protein drugs

    International Nuclear Information System (INIS)

    Zhang, Yan; Yang, Zhijie; Hu, Xi; Zhang, Ling; Li, Feng; Li, Meimei; Tang, Xing; Xiao, Wei

    2015-01-01

    The objective of this study was to develop pH-sensitive Eudragit L100–cysteine/reduced glutathione (Eul–cys/GSH) nanoparticles (NPs), which provided the mucoadhesion and protection for protein drugs against enzymatic degradation. Insulin was chosen as a model biomolecule for testing this system. The Eul–cys conjugate, which was obtained by grafting cysteine onto the carboxy group of Eudragit L100, was analyzed by HNMR and SEM, and the swelling degree (SD), cation binding, and enzymatic inhibition were also determined. The results obtained showed that the Eul–cys conjugate represent a pH-sensitive delivery system which effectively protected the insulin from being degraded by the proteases, and this is related to the mechanism of Ca 2+ binding. Insulin-loaded Eul–cys/GSH NPs were prepared by a diffusion method involving an electrostatic interaction between the network structure of the polymer and the embedded proteins, including insulin and GSH. TEM images indicated that Eul–cys/GSH existed as smooth and spherical NPs in aqueous solution with particle sizes of 260 ± 20 nm. The X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) findings showed the presence of amorphous insulin in thiolated NPs and higher free thiol oxidation than the result obtained by Ellman’s reagent method. In addition, thiolated NPs showed excellent binding efficiency to the mucin in rat intestine, indicating that Eul–cys/GSH NPs have great potential to be applied as safe carriers for the oral administration of protein drugs

  15. Development and evaluation of mucoadhesive nanoparticles based on thiolated Eudragit for oral delivery of protein drugs

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yan [Shenyang University, Normal College (China); Yang, Zhijie; Hu, Xi; Zhang, Ling [Shenyang Pharmaceutical University, Department of Pharmaceutics (China); Li, Feng; Li, Meimei [Shenyang University, Normal College (China); Tang, Xing [Shenyang Pharmaceutical University, Department of Pharmaceutics (China); Xiao, Wei, E-mail: wzhzh-nj@tom.com [Jiangsu Kanion Pharmaceutical Co., Ltd (China)

    2015-02-15

    The objective of this study was to develop pH-sensitive Eudragit L100–cysteine/reduced glutathione (Eul–cys/GSH) nanoparticles (NPs), which provided the mucoadhesion and protection for protein drugs against enzymatic degradation. Insulin was chosen as a model biomolecule for testing this system. The Eul–cys conjugate, which was obtained by grafting cysteine onto the carboxy group of Eudragit L100, was analyzed by HNMR and SEM, and the swelling degree (SD), cation binding, and enzymatic inhibition were also determined. The results obtained showed that the Eul–cys conjugate represent a pH-sensitive delivery system which effectively protected the insulin from being degraded by the proteases, and this is related to the mechanism of Ca{sup 2+} binding. Insulin-loaded Eul–cys/GSH NPs were prepared by a diffusion method involving an electrostatic interaction between the network structure of the polymer and the embedded proteins, including insulin and GSH. TEM images indicated that Eul–cys/GSH existed as smooth and spherical NPs in aqueous solution with particle sizes of 260 ± 20 nm. The X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) findings showed the presence of amorphous insulin in thiolated NPs and higher free thiol oxidation than the result obtained by Ellman’s reagent method. In addition, thiolated NPs showed excellent binding efficiency to the mucin in rat intestine, indicating that Eul–cys/GSH NPs have great potential to be applied as safe carriers for the oral administration of protein drugs.

  16. Development and evaluation of mucoadhesive nanoparticles based on thiolated Eudragit for oral delivery of protein drugs

    Science.gov (United States)

    Zhang, Yan; Yang, Zhijie; Hu, Xi; Zhang, Ling; Li, Feng; Li, Meimei; Tang, Xing; Xiao, Wei

    2015-02-01

    The objective of this study was to develop pH-sensitive Eudragit L100-cysteine/reduced glutathione (Eul-cys/GSH) nanoparticles (NPs), which provided the mucoadhesion and protection for protein drugs against enzymatic degradation. Insulin was chosen as a model biomolecule for testing this system. The Eul-cys conjugate, which was obtained by grafting cysteine onto the carboxy group of Eudragit L100, was analyzed by HNMR and SEM, and the swelling degree (SD), cation binding, and enzymatic inhibition were also determined. The results obtained showed that the Eul-cys conjugate represent a pH-sensitive delivery system which effectively protected the insulin from being degraded by the proteases, and this is related to the mechanism of Ca2+ binding. Insulin-loaded Eul-cys/GSH NPs were prepared by a diffusion method involving an electrostatic interaction between the network structure of the polymer and the embedded proteins, including insulin and GSH. TEM images indicated that Eul-cys/GSH existed as smooth and spherical NPs in aqueous solution with particle sizes of 260 ± 20 nm. The X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) findings showed the presence of amorphous insulin in thiolated NPs and higher free thiol oxidation than the result obtained by Ellman's reagent method. In addition, thiolated NPs showed excellent binding efficiency to the mucin in rat intestine, indicating that Eul-cys/GSH NPs have great potential to be applied as safe carriers for the oral administration of protein drugs.

  17. Thiolated chitosan nanoparticles as an oral delivery system for Amikacin: in vitro and ex vivo evaluations.

    Science.gov (United States)

    Atyabi, F; Talaie, F; Dinarvand, R

    2009-08-01

    The purpose of this study was the synthesis of two thiol conjugated Chitosan polymers, and evaluation of the potential of Thiomer nanoparticle formulation as a carrier for oral delivery system. Mediated by EDAC (Ethylene-3-(3-di-methylaminopropyl)-carbodiimide), either N-acetyl Cysteine (NAC) or N-acetyl D-penicillamine (NAP) were covalently attached to Chitosan. The success of the synthesis was demonstrated by comparing FTIR spectra. Iodometric titration demonstrated that depending on the pH value of the synthesis medium, the Thiomers display 250 +/- 30 microMol and 300 +/- 20 microMol thiol groups per gram of polymer respectively. The interaction between mucin and Thiomers, compared to mucin and Chitosan was studied for assessment of mucoadhesion properties of synthesized polymers. This interaction was determined by the measurement of the amount of mucin adsorbed on Chitosan and the conjugated polymers. Rotating cylinder method demonstrated an average of 20 times improvement in mucoadhesion of Thiomers compared to the unmodified polymer. Chitosan and Thiomer nanoparticles were formulated by two methods; TPP and Sodium Sulfate gelation. SEM micrographs and data achieved by a Malvern nano/zetasizer show nanoparticles formed by TPP gelation have a mean size of 150 +/- 15 nm compared to 300 +/- 25 nm sized nanoparticles obtained by Sodium sulfate gelation. TPP gelation yields smaller, more spherical shaped nanoparticles with a smaller range of size distribution. Amikacin loaded nanoparticles with an average size of 280 nm were prepared by TPP gelation in which disulfide bond formation was achieved by a time dependent oxidation process. In vitro studies were carried out; a recovery rate of 33% and a drug entrapment of 25% were achieved. The amount of release was determined during 18 hr in a carefully prepared media. The permeation time across a biological membrane was observed to be about 150 minutes. Microbiological tests were carried out on two microorganisms

  18. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis.

    Science.gov (United States)

    Xiao, Bo; Xu, Zhigang; Viennois, Emilie; Zhang, Yuchen; Zhang, Zhan; Zhang, Mingzhen; Han, Moon Kwon; Kang, Yuejun; Merlin, Didier

    2017-07-05

    Overcoming adverse effects and selectively delivering drug to target cells are two major challenges in the treatment of ulcerative colitis (UC). Lysine-proline-valine (KPV), a naturally occurring tripeptide, has been shown to attenuate the inflammatory responses of colonic cells. Here, we loaded KPV into hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant HA-KPV-NPs had a desirable particle size (∼272.3 nm) and a slightly negative zeta potential (∼-5.3 mV). These NPs successfully mediated the targeted delivery of KPV to key UC therapy-related cells (colonic epithelial cells and macrophages). In addition, these KPV-loaded NPs appear to be nontoxic and biocompatible with intestinal cells. Intriguingly, we found that HA-KPV-NPs exert combined effects against UC by both accelerating mucosal healing and alleviating inflammation. Oral administration of HA-KPV-NPs encapsulated in a hydrogel (chitosan/alginate) exhibited a much stronger capacity to prevent mucosa damage and downregulate TNF-α, thus they showed a much better therapeutic efficacy against UC in a mouse model, compared with a KPV-NP/hydrogel system. These results collectively demonstrate that our HA-KPV-NP/hydrogel system has the capacity to release HA-KPV-NPs in the colonic lumen and that these NPs subsequently penetrate into colitis tissues and enable KPV to be internalized into target cells, thereby alleviating UC. Copyright © 2016 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  19. Transdermal drug delivery

    OpenAIRE

    Prausnitz, Mark R.; Langer, Robert

    2008-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability ...

  20. Solid self-nanoemulsifying drug delivery systems for oral delivery of polypeptide-k: Formulation, optimization, in-vitro and in-vivo antidiabetic evaluation.

    Science.gov (United States)

    Garg, Varun; Kaur, Puneet; Singh, Sachin Kumar; Kumar, Bimlesh; Bawa, Palak; Gulati, Monica; Yadav, Ankit Kumar

    2017-11-15

    Development of self-nanoemulsifying drug delivery systems (SNEDDS) of polypeptide-k (PPK) is reported with the aim to achieve its oral delivery. Box-Behnken design (BBD) was adopted to develop and optimize the composition of SNEDDS. Oleoyl polyoxyl-6 glycerides (A), Tween 80 (B), and diethylene glycol monoethyl ether (C) were used as oil, surfactant and co-surfactant, respectively as independent variables. The effect of variation in their composition was observed on the mean droplet size (y1), polydispersity index (PDI) (y2), % drug loading (y3) and zeta potential (y4). As per the optimal design, seventeen SNEDDS prototypes were prepared. The optimized composition of SNEDDS formulation was 25% v/v Oleoyl polyoxyl-6 glycerides, 37% v/v Tween 80, 38% v/v diethylene glycol monoethyl ether, and 3% w/v PPK. The optimized formulation revealed values of y1, y2, y3, and y4 as 31.89nm, 0.16, 73.15%, and -15.65mV, respectively. Further the optimized liquid SNEDDS were solidified through spray drying using various hydrophilic and hydrophobic carriers. Among the various carriers, Aerosil 200 was found to provide desirable flow, compression, disintegration and dissolution properties. Both, liquid and solid-SNEDDS have shown release of >90% within 10min. The formulation was found stable with change in pH, dilution, temperature variation and freeze thaw cycles in terms of droplet size, zeta potential, drug precipitation and phase separation. Crystalline PPK was observed in amorphous state in solid SNEDDS when characterized through DSC and PXRD studies. The biochemical, hematological and histopathological results of streptozotocin induced diabetic rats shown promising antidiabetic potential of PPK loaded in SNEDDS at its both the doses (i.e. 400mg/kg and 800mg/kg) as compared to its naïve form at both the doses. The study revealed successful formulation of SNEDDS for oral delivery of PPK. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Role of human papillomavirus in oral squamous cell carcinoma and oral potentially malignant disorders: A review of the literature

    Science.gov (United States)

    Gupta, Shikha; Gupta, Sunita

    2015-01-01

    Human papillomaviruses (HPVs) are epitheliotropic viruses with an affinity for keratinocytes and are principally found in the anogenital tract, urethra, skin, larynx, tracheobronchial and oral mucosa. On the basis of high, but variable frequency of HPV in oral squamous cell carcinoma (OSCC), malignant potential of HPV infection has been hypothesized but not definitely confirmed. The aim of this review was to highlight the genomic structure and possible mechanism of infection and carcinogenesis by HPV in the oral mucosa and to review the frequency of HPV prevalence in OSCC and oral potentially malignant disorders. A computer database search was performed through the use of PubMed from 1994 to 2014. Search keywords used were: HPV and oral cancer, HPV and oral leukoplakia, HPV and oral lichen planus, HPV and OSCC, HPV and verrucous carcinoma, HPV and proliferative verrucous leukoplakia, HPV and oral papilloma. PMID:26097339

  2. Potential fluoride toxicity from oral medicaments: A review

    Directory of Open Access Journals (Sweden)

    Rizwan Ullah

    2017-08-01

    Full Text Available The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, toxic effects, and management of fluoride toxicity. The main aim of this review is to highlight the potential adverse effects of fluoride overdose and poorly understood toxicity. In addition, the related clinical significance of fluoride overdose and toxicity has been discussed.

  3. Potential fluoride toxicity from oral medicaments: A review.

    Science.gov (United States)

    Ullah, Rizwan; Zafar, Muhammad Sohail; Shahani, Nazish

    2017-08-01

    The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, toxic effects, and management of fluoride toxicity. The main aim of this review is to highlight the potential adverse effects of fluoride overdose and poorly understood toxicity. In addition, the related clinical significance of fluoride overdose and toxicity has been discussed.

  4. pH-sensitive chitosan/alginate core-shell nanoparticles for efficient and safe oral insulin delivery.

    Science.gov (United States)

    Mukhopadhyay, Piyasi; Chakraborty, Souma; Bhattacharya, Sourav; Mishra, Roshnara; Kundu, P P

    2015-01-01

    Chitosan-alginate (CS/ALG) nanoparticles were prepared by formation of an ionotropic pre-gelation of an alginate (ALG) core entrapping insulin, followed by chitosan (CS) polyelectrolyte complexation, for successful oral insulin administration. Mild preparation process without harsh chemicals is aimed at improving insulin bio-efficiency in in vivo model. The nanoparticles showed an average particle size of 100-200 nm in dynamic light scattering (DLS), with almost spherical or sub-spherical shape and ∼ 85% of insulin encapsulation. Again, retention of almost entire amount of encapsulated insulin in simulated gastric buffer followed by its sustained release in simulated intestinal condition proved its pH sensitivity in in vitro release studies. Significant hypoglycemic effects with improved insulin-relative bioavailability (∼ 8.11%) in in vivo model revealed the efficacy of these core-shell nanoparticles of CS/ALG as an oral insulin carrier. No systemic toxicity was found after its peroral treatment, suggesting these core-shell nanoparticles as a promising device for potential oral insulin delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Microencapsulation as a novel delivery method for the potential antidiabetic drug, Probucol.

    Science.gov (United States)

    Mooranian, Armin; Negrulj, Rebecca; Chen-Tan, Nigel; Al-Sallami, Hesham S; Fang, Zhongxiang; Mukkur, T K; Mikov, Momir; Golocorbin-Kon, Svetlana; Fakhoury, Marc; Watts, Gerald F; Matthews, Vance; Arfuso, Frank; Al-Salami, Hani

    2014-01-01

    In previous studies, we successfully designed complex multicompartmental microcapsules as a platform for the oral targeted delivery of lipophilic drugs in type 2 diabetes (T2D). Probucol (PB) is an antihyperlipidemic and antioxidant drug with the potential to show benefits in T2D. We aimed to create a novel microencapsulated formulation of PB and to examine the shape, size, and chemical, thermal, and rheological properties of these microcapsules in vitro. Microencapsulation was carried out using the Büchi-based microencapsulating system developed in our laboratory. Using the polymer, sodium alginate (SA), empty (control, SA) and loaded (test, PB-SA) microcapsules were prepared at a constant ratio (1:30). Complete characterizations of microcapsules, in terms of morphology, thermal profiles, dispersity, and spectral studies, were carried out in triplicate. PB-SA microcapsules displayed uniform and homogeneous characteristics with an average diameter of 1 mm. The microcapsules exhibited pseudoplastic-thixotropic characteristics and showed no chemical interactions between the ingredients. These data were further supported by differential scanning calorimetric analysis and Fourier transform infrared spectral studies, suggesting microcapsule stability. The new PB-SA microcapsules have good structural properties and may be suitable for the oral delivery of PB in T2D. Further studies are required to examine the clinical efficacy and safety of PB in T2D.

  6. Self-microemulsifying drug delivery system for improved oral bioavailability of dipyridamole: preparation and evaluation.

    Science.gov (United States)

    Guo, Feng; Zhong, Haijun; He, Jing; Xie, Baogang; Liu, Fen; Xu, Helin; Liu, Minmin; Xu, Chunlian

    2011-07-01

    Dipyridamole shows poor and variable bioavailability after oral administration due to pHdependent solubility, low biomembrane permeability as well as being a substrate of P-glycoprotein. In order to improve the oral absorption of dipyridamole, a self-microemulsifying drug delivery system (SMEDDS) for dipyridamole was prepared and evaluated in vitro and in vivo. The optimum formulation was 18% oleic acid, 12% Labrafac lipophile WL 1349, 42% Solutol HS 15 and 28% isopropyl alcohol. It was found that the performance of self-microemulsification with the combination of oleic acid and Labrafac lipophile WL 1349 increased compared with just one oil. The results obtained from an in vitro dissolution assay indicated that dipyridamole in SMEDDS dissolved rapidly and completely in pH 6.8 aqueous media, while the commercial drug tablet was less soluble. An oral bioavailability study in rats showed that dipyridamole in the SMEDDS formulation had a 2.06-fold increased absorption compared with the simple drug suspension. It was evident that SMEDDS may be an effective approach to improve the oral absorption for drugs having pH-dependent solubility.

  7. An introduction to fast dissolving oral thin film drug delivery systems: a review.

    Science.gov (United States)

    Kathpalia, Harsha; Gupte, Aasavari

    2013-12-01

    Many pharmaceutical companies are switching their products from tablets to fast dissolving oral thin films (OTFs). Films have all the advantages of tablets (precise dosage, easy administration) and those of liquid dosage forms (easy swallowing, rapid bioavailability). Statistics have shown that four out of five patients prefer orally disintegrating dosage forms over conventional solid oral dosages forms. Pediatric, geriatric, bedridden, emetic patients and those with Central Nervous System disorders, have difficulty in swallowing or chewing solid dosage forms. Many of these patients are non-compliant in administering solid dosage forms due to fear of choking. OTFs when placed on the tip or the floor of the tongue are instantly wet by saliva. As a result, OTFs rapidly hydrate and then disintegrate and/or dissolve to release the medication for local and/or systemic absorption. This technology provides a good platform for patent non- infringing product development and for increasing the patent life-cycle of the existing products. The application of fast dissolving oral thin films is not only limited to buccal fast dissolving system, but also expands to other applications like gastroretentive, sublingual delivery systems. This review highlights the composition including the details of various types of polymers both natural and synthetic, the different types of manufacturing techniques, packaging materials and evaluation tests for the OTFs.

  8. Electrospun fish protein fibers as a biopolymer-based carrier – implications for oral protein delivery

    DEFF Research Database (Denmark)

    Boutrup Stephansen, Karen; García-Díaz, María; Jessen, Flemming

    2014-01-01

    Purpose: Protein-based electrospun fibers have emerged as novel nanostructured materials for tissue engineering and drug delivery due to their unique structural characteristics, biocompatibility and biodegradability. The aim of this study was to explore the use of electrospun fibers based on fish...... sarcoplasmic proteins as an oral delivery platform for biopharmaceuticals, using insulin as a model protein. Methods: Fish sarcoplasmic proteins (FSP) were isolated from fresh cod and electrospun into nanomicrofibers using insulin as a model payload. The morphology of FSP fibers was characterized using...... differentiated Caco-2 cell monolayers was followed by RP-HPLC and ELISA, and the transepithelial electrical resistance (TEER) was measured before and after the experiment. Cell viability was assessed by the MTS/PMS assay. Results: Insulin was encapsulated in the electrospun FSP fibers with high efficiency, high...

  9. Potential applications for halloysite nanotubes based drug delivery systems

    Science.gov (United States)

    Sun, Lin

    Drug delivery refers to approaches, formulations, technologies, and systems for transporting a drug in the body. The purpose is to enhance the drug efficacy and to reduce side reactions, which can significantly improve treatment outcomes. Halloysite is a naturally occurred alumino-silicate clay with a tubular structure. It is a biocompatible material with a big surface area which can be used for attachment of targeted molecules. Besides, loaded molecules can present a sustained release manner in solution. These properties make halloysite nanotubes (HNTs) a good option for drug delivery. In this study, a drug delivery system was built based on halloysite via three different fabrication methods: physical adsorption, vacuum loading and layer-by-layer coating. Methotrexate was used as the model drug. Factors that may affect performance in both drug loading and release were tested. Results showed that methotrexate could be incorporated within the HNTs system and released in a sustained manner. Layer-by-layer coating showed a better potential than the other two methods in both MTX loading and release. Besides, lower pH could greatly improve MTX loading and release while the increased number of polyelectrolytes bilayers had a limited impact. Osteosarcoma is the most common primary bone malignancy in children and adolescents. Postoperative recurrence and metastasis has become one of the leading causes for patient death after surgical remove of the tumor mass. A strategy could be a sustained release of chemotherapeutics directly at the primary tumor sites where recurrence would mostly occur. Then, this HNTs based system was tested with osteosarcoma cells in vitro to show the potential of delivering chemotherapeutics in the treatment of osteosarcoma. Methotrexate was incorporated within HNTs with a layer-bylayer coating technique, and drug coated HNTs were filled into nylon-6 which is a common material for surgical sutures in industry. Results showed that (1) methotrexate

  10. Exhaled breath and oral cavity VOCs as potential biomarkers in oral cancer patients.

    Science.gov (United States)

    Bouza, M; Gonzalez-Soto, J; Pereiro, R; de Vicente, J C; Sanz-Medel, A

    2017-03-01

    Corporal mechanisms attributed to cancer, such as oxidative stress or the action of cytochrome P450 enzymes, seem to be responsible for the generation of a variety of volatile organic compounds (VOCs) that could be used as non-invasive diagnosis biomarkers. The present work presents an attempt to use VOCs from exhaled breath and oral cavity air as biomarkers for oral squamous cell carcinoma (OSCC) patients. A total of 52 breath samples were collected (in 3 L Tedlar bags) from 26 OSCC patients and 26 cancer-free controls. The samples were analyzed using solid-phase microextraction followed by gas chromatography-mass spectrometry detection. Different statistical strategies (e.g., Icoshift, SIMCA, LDA, etc) were used to classify the analytical data. Results revealed that compounds such as undecane, dodecane, decanal, benzaldehyde, 3,7-dimethyl undecane, 4,5-dimethyl nonane, 1-octene, and hexadecane had relevance as possible biomarkers for OSCC. LDA classification with these compounds showed well-defined clusters for patients and controls (non-smokers and smokers). In addition to breath analysis, preliminary studies were carried out to evaluate the possibility of lesion-surrounded air (analyzed OSCC tumors are in the oral cavity) as a source of biomarkers. The oral cavity location of the squamous cell carcinoma tumors constitutes an opportunity to non-invasively collect the air surrounding the lesion. Small quantities (20 ml) of air collected in the oral cavity were analyzed using the above methodology. Results showed that aldehydes present in the oral cavity might constitute potential OSCC biomarkers.

  11. The challenges and future of oral drug delivery: An interview with David Brayden.

    Science.gov (United States)

    Brayden, David J

    2016-12-01

    David Brayden speaks to Hannah Makin, Commissioning Editor: David Brayden is a Full Professor (Advanced Drug Delivery) at the School of Veterinary Medicine, University College Dublin (UCD) and also a Fellow of the UCD Conway Institute. Following a PhD in Pharmacology at the University of Cambridge, UK (1989), and a postdoctoral research fellowship at Stanford University, CA, USA, he set up Elan Biotechnology Research's in vitro pharmacology laboratory in Dublin (1991). At Elan, he became a senior scientist and project manager of several of Elan's joint-venture drug delivery research collaborations with US biotech companies. In 2001, he joined UCD as a lecturer in veterinary pharmacology and was appointed Associate Professor in 2006 and Full Professor in 2014. He was a Director of the Science Foundation Ireland Research Cluster (The Irish Drug Delivery Research Network) from 2007 to 2013, is a Deputy Coordinator of an FP7 Consortium on oral peptides in nanoparticles ('TRANS-INT', 2012-2017), and is a Co-Principal Investigator in 'CURAM', Science Foundation Ireland's new Centre for Medical Devices (2014-2020 [ 1 ]). He was made a Fellow of the Controlled Release Society in 2012. He is the author or co-author of >200 research publications and patents. D Brayden serves on the Editorial Advisory Boards of Drug Discovery Today, European Journal of Pharmaceutical Sciences, Advanced Drug Delivery Reviews and the Journal of Veterinary Pharmacology and Therapeutics, and is an Associate Editor of Therapeutic Delivery. D Brayden works as an independent consultant for drug delivery companies.

  12. An oral delivery system for indomethicin engineered from cationic lipid emulsions and silica nanoparticles

    DEFF Research Database (Denmark)

    Simovic, Spomenka; Hui, He; Song, Yunmei

    2010-01-01

    We report on a porous silica-lipid hybrid microcapsule (SLH) oral delivery system for indomethacin fabricated from Pickering emulsion templates, where the drug forms an electrostatic complex with cationic lipid present in the oil phase. Dry SLH microcapsules prepared either by spray drying...... (approximately 1-5 microm) or phase coacervation (20-50 microm) exhibit a specific internal porous matrix structure with pore diameters in the range of 20 to 100 nm. Dissolution studies under sink conditions and in the presence of electrolytes revealed a decreased extent of dissolution; this confirms...

  13. Self-assembled lecithin/chitosan nanoparticles for oral insulin delivery: preparation and functional evaluation

    Directory of Open Access Journals (Sweden)

    Liu LY

    2016-02-01

    Full Text Available Liyao Liu, Cuiping Zhou, Xuejun Xia, Yuling Liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China Purpose: Here, we investigated the formation and functional properties of self-assembled lecithin/chitosan nanoparticles (L/C NPs loaded with insulin following insulin–phospholipid complex preparation, with the aim of developing a method for oral insulin delivery.Methods: Using a modified solvent-injection method, insulin-loaded L/C NPs were obtained by combining insulin–phospholipid complexes with L/C NPs. The nanoparticle size distribution was determined by dynamic light scattering, and morphologies were analyzed by cryogenic transmission electron microscopy. Fourier transform infrared spectroscopy analysis was used to disclose the molecular mechanism of prepared insulin-loaded L/C NPs. Fast ultrafiltration and a reversed-phase high-performance liquid chromatography assay were used to separate free insulin from insulin entrapped in the L/C NPs, as well as to measure the insulin-entrapment and drug-loading efficiencies. The in vitro release profile was obtained, and in vivo hypoglycemic effects were evaluated in streptozotocin-induced diabetic rats.Results: Our results indicated that insulin-containing L/C NPs had a mean size of 180 nm, an insulin-entrapment efficiency of 94%, and an insulin-loading efficiency of 4.5%. Cryogenic transmission electron microscopy observations of insulin-loaded L/C NPs revealed multilamellar structures with a hollow core, encircled by several bilayers. In vitro analysis revealed that insulin release from L/C NPs depended on the L/C ratio. Insulin-loaded L/C NPs orally administered to streptozotocin-induced diabetic rats exerted a significant

  14. Future Organization of Oral Health Services Delivery: From 2012 to 2042.

    Science.gov (United States)

    Brown, L Jackson

    2017-09-01

    The United States is currently experiencing a vortex of change in both general health and oral health care delivery, the ultimate outcome of which is still not well understood. The specific focus of this article is to examine the future organization of the oral health services delivery system (OHSDS) in the U.S., with special attention given to the role of large group dental practices (LGDPs) in that future. The article describes the various types of LGDPs and their ability to change the economic characteristics of the OHSDS. Large geographically distributed corporate group dental practices (LGDCGDPs) are the type that may expand their market share to the extent that they could change the economic characteristics of the OHSDS. A wide range of scenarios is used to project the expansion of LGDCGDPs into the future. The scenarios modeled are not intended as predictions but rather to present a range of possible OHSDS market structures that may emerge over the next 30 years. The implications of each scenario for the economic competition within the OHSDS are described. Possible implications of these trends for dental education are also discussed. This article was written as part of the project "Advancing Dental Education in the 21 st Century."

  15. Compartmentalized Metabolic Engineering for Artemisinin Biosynthesis and Effective Malaria Treatment by Oral Delivery of Plant Cells.

    Science.gov (United States)

    Malhotra, Karan; Subramaniyan, Mayavan; Rawat, Khushboo; Kalamuddin, Md; Qureshi, M Irfan; Malhotra, Pawan; Mohmmed, Asif; Cornish, Katrina; Daniell, Henry; Kumar, Shashi

    2016-11-07

    Artemisinin is highly effective against drug-resistant malarial parasites, which affects nearly half of the global population and kills >500 000 people each year. The primary cost of artemisinin is the very expensive process used to extract and purify the drug from Artemisia annua. Elimination of this apparently unnecessary step will make this potent antimalarial drug affordable to the global population living in endemic regions. Here we reported the oral delivery of a non-protein drug artemisinin biosynthesized (∼0.8 mg/g dry weight) at clinically meaningful levels in tobacco by engineering two metabolic pathways targeted to three different cellular compartments (chloroplast, nucleus, and mitochondria). The doubly transgenic lines showed a three-fold enhancement of isopentenyl pyrophosphate, and targeting AACPR, DBR2, and CYP71AV1 to chloroplasts resulted in higher expression and an efficient photo-oxidation of dihydroartemisinic acid to artemisinin. Partially purified extracts from the leaves of transgenic tobacco plants inhibited in vitro growth progression of Plasmodium falciparum-infected red blood cells. Oral feeding of whole intact plant cells bioencapsulating the artemisinin reduced the parasitemia levels in challenged mice in comparison with commercial drug. Such novel synergistic approaches should facilitate low-cost production and delivery of artemisinin and other drugs through metabolic engineering of edible plants. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

  16. Cyclodextrin-insulin complex encapsulated polymethacrylic acid based nanoparticles for oral insulin delivery.

    Science.gov (United States)

    Sajeesh, S; Sharma, Chandra P

    2006-11-15

    Present investigation was aimed at developing an oral insulin delivery system based on hydroxypropyl beta cyclodextrin-insulin (HPbetaCD-I) complex encapsulated polymethacrylic acid-chitosan-polyether (polyethylene glycol-polypropylene glycol copolymer) (PMCP) nanoparticles. Nanoparticles were prepared by the free radical polymerization of methacrylic acid in presence of chitosan and polyether in a solvent/surfactant free medium. Dynamic light scattering (DLS) experiment was conducted with particles dispersed in phosphate buffer (pH 7.4) and size distribution curve was observed in the range of 500-800 nm. HPbetaCD was used to prepare non-covalent inclusion complex with insulin and complex was analyzed by Fourier transform infrared (FTIR) and fluorescence spectroscopic studies. HPbetaCD complexed insulin was encapsulated into PMCP nanoparticles by diffusion filling method and their in vitro release profile was evaluated at acidic/alkaline pH. PMCP nanoparticles displayed good insulin encapsulation efficiency and release profile was largely dependent on the pH of the medium. Enzyme linked immunosorbent assay (ELISA) study demonstrated that insulin encapsulated inside the particles was biologically active. Trypsin inhibitory effect of PMCP nanoparticles was evaluated using N-alpha-benzoyl-L-arginine ethyl ester (BAEE) and casein as substrates. Mucoadhesive studies of PMCP nanoparticles were conducted using freshly excised rat intestinal mucosa and the particles were found fairly adhesive. From the preliminary studies, cyclodextrin complexed insulin encapsulated mucoadhesive nanoparticles appear to be a good candidate for oral insulin delivery.

  17. Thiol functionalized polymethacrylic acid-based hydrogel microparticles for oral insulin delivery.

    Science.gov (United States)

    Sajeesh, S; Vauthier, C; Gueutin, C; Ponchel, G; Sharma, Chandra P

    2010-08-01

    In the present study thiol functionalized polymethacrylic acid-polyethylene glycol-chitosan (PCP)-based hydrogel microparticles were utilized to develop an oral insulin delivery system. Thiol modification was achieved by grafting cysteine to the activated surface carboxyl groups of PCP hydrogels (Cys-PCP). Swelling and insulin loading/release experiments were conducted on these particles. The ability of these particles to inhibit protease enzymes was evaluated under in vitro experimental conditions. Insulin transport experiments were performed on Caco-2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up. Finally, the efficacy of insulin-loaded particles in reducing the blood glucose level in streptozotocin-induced diabetic rats was investigated. Thiolated hydrogel microparticles showed less swelling and had a lower insulin encapsulation efficiency as compared with unmodified PCP particles. PCP and Cys-PCP microparticles were able to inhibit protease enzymes under in vitro conditions. Thiolation was an effective strategy to improve insulin absorption across Caco-2 cell monolayers, however, the effect was reduced in the experiments using excised rat intestinal tissue. Nevertheless, functionalized microparticles were more effective in eliciting a pharmacological response in diabetic animal, as compared with unmodified PCP microparticles. From these studies thiolation of hydrogel microparticles seems to be a promising approach to improve oral delivery of proteins/peptides. Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  18. Development and evaluation of polymer nanoparticles for oral delivery of estradiol to rat brain in a model of Alzheimer's pathology.

    Science.gov (United States)

    Mittal, G; Carswell, H; Brett, R; Currie, S; Kumar, M N V Ravi

    2011-03-10

    The purpose of this study was to develop tween 80 (T-80) coated polylactide-co-glycolide (PLGA) nanoparticles that can deliver estradiol to the brain upon oral administration. Estradiol containing nanoparticles were made by a single emulsion technique and T-80 coating was achieved by incubating the re-constituted nanoparticles at different concentrations of T-80. The process of T-80 coating on the nanoparticles was optimized and the pharmacokinetics of estradiol nanoparticles was studied as a function of T-80 coating. The nanoparticles were then evaluated in an ovariectomized (OVX) rat model of Alzheimer's disease (AD) that mimics the postmenopausal conditions. The nanoparticles bound T-80 were found to proportionally increase from 9.72 ± 1.07 mg to 63.84 ± 3.59 mg with an increase in the initial concentration T-80 from 1% to 5% and were stable in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Orally administered T-80 coated nanoparticles resulted in significantly higher brain estradiol levels after 24h (1.969 ± 0.197 ng/g tissue) as compared to uncoated ones (1.105 ± 0.136 ng/g tissue) at a dose of 0.2mg/rat, suggesting a significant role of surface coating. Moreover, these brain estradiol levels were almost similar to those obtained after administration of the same dose of drug suspension via 100% bioavailable intramuscular route (2.123 ± 0.370 ng/g tissue), indicating the increased fraction of bioavailable drug reaching the brain when administered orally. Also, the nanoparticle treated group was successful in preventing the expression of amyloid beta-42 (Aβ42) immunoreactivity in the hippocampus region of brain. Together, the results indicate the potential of nanoparticles for oral delivery of estradiol to brain. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Immune response induced by oral delivery of Bacillus subtilis spores expressing enolase of Clonorchis sinensis in grass carps (Ctenopharyngodon idellus).

    Science.gov (United States)

    Jiang, Hongye; Chen, Tingjin; Sun, Hengchang; Tang, Zeli; Yu, Jinyun; Lin, Zhipeng; Ren, Pengli; Zhou, Xinyi; Huang, Yan; Li, Xuerong; Yu, Xinbing

    2017-01-01

    Clonorchiasis, caused by the consumption of raw or undercooked freshwater fish containing infective metacercariae of Clonorchis sinensisis (C.sinensis), remains a common public health problem. New effective prevention strategies are still urgent to control this food-borne infectious disease. The previous studies suggested Bacillus subtilis (B. subtilis) spores was an ideal vaccines delivery system, and the C.sinensis enolase (CsENO) was a potential vaccine candidate against clonorchiasis. In the current study, we detected CsENO-specific IgM levels by ELISA in sera, intestinal mucus and skin mucus in grass carps (Ctenopharyngodon idella) through oral administration with B. subtilis spores surface expressing CsENO. In addition, immune-related genes expression was also measured by qRT-PCR. Grass carps orally treated with B. subtilis spores or normal forages were used as controls. The results of ELISA manifested that specific IgM levels of grass carps in CsENO group in sera, intestine mucus and skin mucus almost significantly increased from week 4 post the first oral administration when compared to the two control groups. The levels of specific IgM reached its peak in intestine mucus firstly, then in sera, and last in skin mucus. qRT-PCR results showed that 5 immune-related genes expression had different degree of rising trend in CsENO group when compared to the two control groups. Our study demonstrated that orally administrated with B. subtilis spores expressing CsENO induced innate and adaptive immunity, systemic and local mucosal immunity, and humoral and cellular immunity. Our work may pave the way to clarify the exact mechanisms of protective efficacy elicited by B. subtilis spores expressing CsENO and provide new ideas for vaccine development against C. sinensis infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Zirconium Phosphate Nanoplatelet Potential for Anticancer Drug Delivery Applications.

    Science.gov (United States)

    González, Millie L; Ortiz, Mayra; Hernández, Carmen; Cabán, Jennifer; Rodríguez, Axel; Colón, Jorge L; Báez, Adriana

    2016-01-01

    Zirconium phosphate (ZrP) nanoplatelets can intercalate anticancer agents via an ion exchange reaction creating an inorganic delivery system with potential for cancer treatment. ZrP delivery of anticancer agents inside tumor cells was explored in vitro. Internalization and cytotoxicity of ZrP nanoplatelets were studied in MCF-7 and MCF-10A cells. DOX-loaded ZrP nanoplatelets (DOX@ZrP) uptake was assessed by confocal (CLSM) and transmission electron microscopy (TEM). Cytotoxicity to MCF-7 and MCF-10A cells was determined by the MTT assay. Reactive Oxy- gen Species (ROS) production was analyzed by fluorometric assay, and cell cycle alterations and induction of apoptosis were analyzed by flow cytometry. ZrP nanoplatelets were localized in the endosomes of MCF-7 cells. DOX and ZrP nanoplatelets were co-internalized into MCF-7 cells as detected by CLSM. While ZrP showed limited toxicity to MCF-7 cells, DOX@ZrP was cytotoxic at an IC₅₀ similar to that of free DOX. Meanwhile, DOX lC₅₀ was significantly lower than the equivalent concentration of DOX@ZrP in MCF-10A cells. ZrP did not induce apoptosis in both cell lines. DOX and DOX@ZrP induced significant oxidative stress in both cell models. Results suggest that ZrP nanoplatelets are promising as carriers of anticancer agents into cancer cells.

  1. Potential and problems in ultrasound-responsive drug delivery systems

    Directory of Open Access Journals (Sweden)

    Zhao YZ

    2013-04-01

    Full Text Available Ying-Zheng Zhao,1,3 Li-Na Du,2 Cui-Tao Lu,1 Yi-Guang Jin,2 Shu-Ping Ge3 1Wenzhou Medical College, Wenzhou City, Zhejiang Province, 2Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China; 3St Christopher’s Hospital for Children/Drexel University College of Medicine, Philadelphia, PA, USA Abstract: Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. Keywords: ultrasound, targeted therapy, clinical application

  2. Lipid Nanocarriers for Oral Delivery of Serenoa repens CO2 Extract: A Study of Microemulsion and Self-Microemulsifying Drug Delivery Systems.

    Science.gov (United States)

    Guccione, Clizia; Bergonzi, Maria Camilla; Awada, Khaled M; Piazzini, Vieri; Bilia, Anna Rita

    2018-07-01

    The aim of this study was the development and characterization of lipid nanocarriers using food grade components for oral delivery of Serenoa repens CO 2 extract, namely microemulsions (MEs) and self-microemulsifying drug delivery systems (SMEDDSs) to improve the oral absorption. A commercial blend (CB) containing 320 of S. repens CO 2 extract plus the aqueous soluble extracts of nettle root and pineapple stem was formulated in two MEs and two SMEDDSs. The optimized ME loaded with the CB (CBM2) had a very low content of water (only 17.3%). The drug delivery systems were characterized by dynamic light scattering, transmission electron microscopy, and high-performance liquid chromatography (HPLC) with a diode-array detector analyses in order to evaluate the size, the homogeneity, the morphology, and the encapsulation efficiency. β -carotene was selected as marker for the quantitative HPLC analysis. Additionally, physical and chemical stabilities were acceptable during 3 wk at 4 °C. Stability of these nanocarriers in simulated stomach and intestinal conditions was proved. Finally, the improvement of oral absorption of S. repens was studied in vitro using parallel artificial membrane permeability assay. An enhancement of oral permeation was found in both CBM2 and CBS2 nanoformulations comparing with the CB and S. repens CO 2 extract. The best performance was obtained by the CBM2 nanoformulation (~ 17%) predicting a 30 - 70% passive oral human absorption in vivo . Georg Thieme Verlag KG Stuttgart · New York.

  3. Potential effect of cationic liposomes on interactions with oral bacterial cells and biofilms.

    Science.gov (United States)

    Sugano, Marika; Morisaki, Hirobumi; Negishi, Yoichi; Endo-Takahashi, Yoko; Kuwata, Hirotaka; Miyazaki, Takashi; Yamamoto, Matsuo

    2016-01-01

    Although oral infectious diseases have been attributed to bacteria, drug treatments remain ineffective because bacteria and their products exist as biofilms. Cationic liposomes have been suggested to electrostatically interact with the negative charge on the bacterial surface, thereby improving the effects of conventional drug therapies. However, the electrostatic interaction between oral bacteria and cationic liposomes has not yet been examined in detail. The aim of the present study was to examine the behavior of cationic liposomes and Streptococcus mutans in planktonic cells and biofilms. Liposomes with or without cationic lipid were prepared using a reverse-phase evaporation method. The zeta potentials of conventional liposomes (without cationic lipid) and cationic liposomes were -13 and 8 mV, respectively, and both had a mean particle size of approximately 180 nm. We first assessed the interaction between liposomes and planktonic bacterial cells with a flow cytometer. We then used a surface plasmon resonance method to examine the binding of liposomes to biofilms. We confirmed the binding behavior of liposomes with biofilms using confocal laser scanning microscopy. The interactions between cationic liposomes and S. mutans cells and biofilms were stronger than those of conventional liposomes. Microscopic observations revealed that many cationic liposomes interacted with the bacterial mass and penetrated the deep layers of biofilms. In this study, we demonstrated that cationic liposomes had higher affinity not only to oral bacterial cells, but also biofilms than conventional liposomes. This electrostatic interaction may be useful as a potential drug delivery system to biofilms.

  4. Lipid nanoparticles of zaleplon for improved oral delivery by Box-Behnken design: optimization, in vitro and in vivo evaluation.

    Science.gov (United States)

    Dudhipala, Narendar; Janga, Karthik Yadav

    2017-07-01

    Zaleplon (ZL) is a hypnotic drug prescribed for the management of insomnia and convulsions. The oral bioavailability of ZL was low (∼30%) owing to poor water solubility and hepatic first-pass metabolism. The cornerstone of this investigation is to develop and optimize solid lipid nanoparticles (SLNs) of ZL with the aid of Box-Behnken design (BBD) to improve the oral bioavailability. A design space with three formulation variables at three levels were evaluated in BBD. Amount of lipid (A 1 ), amount of surfactant (A 2 ) and concentration of co-surfactant (%) (A 3 ) were selected as independent variables, whereas, particle size (B 1 ), entrapment efficiency (B 2 ) and zeta potential (ZP, B 3 ) as responses. ZL-SLNs were prepared by hot homogenization with ultrasonication method and evaluated for responses to obtain optimized formulation. Morphology of nanoparticles was observed under SEM. DSC and XRD studies were examined to understand the native crystalline behavior of drug in SLN formulations. Further, in vivo studies were performed in Wistar rats. The optimized formulation with 132.89 mg of lipid, 106.7 mg of surfactant and 0.2% w/v of co-surfactant ensued in the nanoparticles with 219.9 ± 3.7 nm of size, -25.66 ± 2.83 mV surface charge and 86.83 ± 2.65% of entrapment efficiency. SEM studies confirmed the spherical shape of SLN formulations. The DSC and XRD studies revealed the transformation of crystalline drug to amorphous form in SLN formulation. In conclusion, in vivo studies in male Wistar rats demonstrated an improvement in the oral bioavailability of ZL from SLN over control ZL suspension. The enhancement in the oral bioavailability of ZL from SLNs, developed with the aid of BBD, explicated the potential of lipid-based nanoparticles as a potential carrier in improving the oral delivery of this poorly soluble drug.

  5. Design of microemulsion system suitable for the oral delivery of poorly aqueous soluble beta-carotene.

    Science.gov (United States)

    Peng, Cheng; Svirskis, Darren; Lee, Sung Je; Oey, Indrawati; Kwak, Hae-Soo; Chen, Guanyu; Bunt, Craig; Wen, Jingyuan

    2017-02-14

    Beta-carotene is a potent antioxidant for maintaining human health. However, its oral absorption is low due to poor aqueous solubility of less than 1 μg/ml. A microemulsion delivery system was designed to solubilize beta-carotene toward enhancing its oral bioavailability. From seven pseudoternary diagrams constructed, three systems were selected with large microemulsion areas suitable for oral administration and dilution in the predominately aqueous gastrointestinal fluids. Conductivity and rheology characterization were conducted along four dilution lines within the selected systems. Three pseudoternary-phase diagrams were selected with large microemulsion regions, >60% of the total phase diagram area, which provide microemulsions with higher drug-loading capacity. A phenomenon was observed by which both propylene glycol and Capmul MCM EP stabilize the microstructure of the microemulsions has been proposed based on the characterization studies. An optimal bicontinuous microemulsion formulation was selected comprising 12% orange oil, 24% Capmul MCM, 18% Tween 20, 6% Labrasol, 20% propylene glycol and 20% water, with a high beta-carotene loading capacity of 140.8 μg/ml and droplet size of 117.4 nm. In conclusion, the developed novel microemulsion formulation allows solubilizing beta-carotene and is a promising basis for further development as a functional beverage.

  6. Antibody response in animals immunized after oral delivery of attenuated liver hepatitis a vaccine

    International Nuclear Information System (INIS)

    Long Runxiang; Hou Zongliu; Xie Zhongping; Ding Xuefeng; Pan Yue; Huang Cheng; Zhang Ming; Yang Lixian

    2006-01-01

    The microspheres were prepared by encapsulating live attenuated hepatitis A vaccine with PLA/PLG, and the rhesus monkeys and mice were immunized by such microspheres through oral route. Then serum was collected to detect the HAV-IgM, HAV-IgG, HAV-IgA with EIA, so as to find a convenient immunization way. Results showed that HAV-IgG in rhesus monkeys was detected in the 3rd week and reached a peak value (1267mlU/mL), and then decreased by degrees. HAV-IgM titer was 1:4000. After an oral booster was given, the HAV-IgG level increased, and HAV-IgM titer was 1:1000. The level reached 1244mIU/mL after challenge with wild virus strain, and HAV-IgM was 1:100. HAV-IgM was detected in the control group only after challenge with wild virus strain. HAV-IgG in mice was detected in the 2nd week and reached a peak value in the 4th week. HAV S-IgA was detected in the 1st week and reached a peak value in the 4th week. Antibody response was induced in the rhesus monkeys after oral delivery of the biodegradable microspheres containing live attenuated HA vaccine. The results in mice were similar with the report but the anti-HAV was present earlier as compared with rhesus monkeys. (authors)

  7. A review on oral liquid as an emerging technology in controlled drug delivery system.

    Science.gov (United States)

    Torne, Sangmesh Raosaheb; Sheela, Angappan; Sarada, N C

    2017-12-03

    The oral liquid drug delivery system (OLDDS) remains as the primary choice of dosage form, though challenging, for the pharmaceutical scientists. In the last two decades, Oral Liquid Controlled Release (OLCR) formulation has gained a lot of attention because of its advantages over the conventional dosage forms. The world of nanotechnology has paved multiple ways to administer the drug through oral cavity in liquid dosage form with an additional advantage of control over the release. In the current study, the various approaches towards the same have been discussed comprehensively to understand the different mechanisms of OLCR. This review also emphasizes on the existing techniques and the developments that have been made to improve on its efficacy including various formulation related factors. It also provides valuable insights into the role of polymers in the development of OLCR formulation that can be used in the management of Gastroesophageal reflux disease (GERD). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Preparation and evaluation of chitosan-based nanogels/gels for oral delivery of myricetin.

    Science.gov (United States)

    Yao, Yashu; Xia, Mengxin; Wang, Huizhen; Li, Guowen; Shen, Hongyi; Ji, Guang; Meng, Qianchao; Xie, Yan

    2016-08-25

    A novel nanogel/gel based on chitosan (CS) for the oral delivery of myricetin (Myr) was developed and evaluated comprehensively. The particle size of the obtained Myr-loaded CS/β-glycerol phosphate (β-GP) nanogels was in the range of 100-300nm. The rheological tests showed that the sol-gel transition happened when the nanogels were exposed to physiological temperatures, and 3D network structures of the gelatinized nanogels (gels) were confirmed by Scanning Electron Microscopy. Myr was released from CS/β-GP nanogel/gel in acidic buffers via a Fickian mechanism, and this release was simultaneously accompanied by swelling and erosion. Moreover, the nanogel/gel exhibited no cytotoxicity by MTT assay, and the oral bioavailability of Myr in rats was improved with an accelerated absorption rate after Myr was loaded into CS/β-GP nanogel/gel. In summary, all of the above showed that CS/β-GP nanogel/gel was an excellent system for orally delivering Myr. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. [Potential of cell penetrating peptides for cell drug delivery].

    Science.gov (United States)

    Poillot, Cathy; De Waard, Michel

    2011-05-01

    The interest of the scientific community for cell penetrating peptides (CPP) has been growing exponentially for these last years, and the list of novel CPP is increasing. These peptides are powerful tools for the delivery of cargoes to their site of action. Indeed, several drugs that cannot translocate through the cell plasma membrane have been successfully delivered into cells when grafted to a CPP. Various cargoes have been linked to CPP, such as oligonucleotides, pharmacologically active drugs, contrast agents for imaging, or nanoparticles as platforms for multigrafting purposes… This review illustrates the fabulous potential of CPP and the diversity of their use, but their most interesting application appears their future clinical use for the treatment of various pathological conditions. © 2011 médecine/sciences - Inserm / SRMS.

  10. Development of oral food-grade delivery systems: current knowledge and future challenges.

    Science.gov (United States)

    Benshitrit, Revital Cohen; Levi, Carmit Shani; Tal, Sharon Levi; Shimoni, Eyal; Lesmes, Uri

    2012-01-01

    In recent years there has been an increasing interest in the development of new and efficient oral food delivery systems as tools to prevent disease and promote human health and well-being. Such vehicles are sought to protect bioactive ingredients added to food while controlling and targeting their release as they pass through the human gastrointestinal tract (GIT). This review aims to summarize the key concepts of food delivery systems, their characterization and evaluation. Particularly, evaluation of their performance within the human GIT is discussed. To this end an overview of several in vivo and in vitro methods currently applied for the study of such systems is given. Although considered to be still in its infancy, this promising field of research is likely to infiltrate into real products through rational design. In order for such efforts to materialize into real products some challenges still need to be met and are discussed herein. Overall, it seems that adopting a comprehensive pharmacological approach and relevant cutting edge tools are likely to facilitate innovations and help elucidate and perhaps tailor delivery systems' behavior in the human GIT.

  11. Carbon nanotubes buckypapers for potential transdermal drug delivery

    International Nuclear Information System (INIS)

    Schwengber, Alex; Prado, Héctor J.; Zilli, Darío A.; Bonelli, Pablo R.

    2015-01-01

    Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT–drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect. - Highlights: • Drug loaded buckypapers from carbon nanotubes were prepared and characterized. • Their potentialities for transdermal drug delivery applications were evaluated. • Characteristics of carbon nanotubes and the structure of the drug affected release • A higher carbon nanotube:drug mass ratio decelerated release • Up to one week controlled release profiles were obtained for the drug flurbiprofen

  12. Carbon nanotubes buckypapers for potential transdermal drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Schwengber, Alex [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Prado, Héctor J. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Cátedra de Tecnología Farmacéutica II, Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, C1033AAJ Buenos Aires (Argentina); Zilli, Darío A. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Bonelli, Pablo R. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, C1033AAJ Buenos Aires (Argentina); and others

    2015-12-01

    Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT–drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect. - Highlights: • Drug loaded buckypapers from carbon nanotubes were prepared and characterized. • Their potentialities for transdermal drug delivery applications were evaluated. • Characteristics of carbon nanotubes and the structure of the drug affected release • A higher carbon nanotube:drug mass ratio decelerated release • Up to one week controlled release profiles were obtained for the drug flurbiprofen.

  13. In vivo evaluation of an oral salmon calcitonin-delivery system based on a thiolated chitosan carrier matrix.

    Science.gov (United States)

    Guggi, Davide; Kast, Constantia E; Bernkop-Schnürch, Andreas

    2003-12-01

    To develop and evaluate an oral delivery system for salmon calcitonin. 2-Iminothiolane was covalently bound to chitosan in order to improve the mucoadhesive and cohesive properties of the polymer. The resulting chitosan-TBA conjugate (chitosan-4-thiobutylamidine conjugate) was homogenized with salmon calcitonin. mannitol, and a chitosan-Bowman-Birk inhibitor conjugate and a chitosan-elastatinal conjugate (6.75 + 0.25 + 1 + 1 + 1). Optionally 0.5% (m/m) reduced glutathione. used as permeation mediator, was added. Each mixture was compressed to 2 mg microtablets and enteric coated with a polymethacrylate. Biofeedback studies were performed in rats by oral administration of the delivery system and determination of the decrease in plasma calcium level as a function of time. Test formulations led to a significant (p thiolated chitosan, chitosan-enzyme-inhibitor conjugates and the permeation mediator glutathione seems to represent a promising strategy for the oral delivery of salmon calcitonin.

  14. Self-assembled lecithin/chitosan nanoparticles for oral insulin delivery: preparation and functional evaluation

    Science.gov (United States)

    Liu, Liyao; Zhou, Cuiping; Xia, Xuejun; Liu, Yuling

    2016-01-01

    Purpose Here, we investigated the formation and functional properties of self-assembled lecithin/chitosan nanoparticles (L/C NPs) loaded with insulin following insulin–phospholipid complex preparation, with the aim of developing a method for oral insulin delivery. Methods Using a modified solvent-injection method, insulin-loaded L/C NPs were obtained by combining insulin–phospholipid complexes with L/C NPs. The nanoparticle size distribution was determined by dynamic light scattering, and morphologies were analyzed by cryogenic transmission electron microscopy. Fourier transform infrared spectroscopy analysis was used to disclose the molecular mechanism of prepared insulin-loaded L/C NPs. Fast ultrafiltration and a reversed-phase high-performance liquid chromatography assay were used to separate free insulin from insulin entrapped in the L/C NPs, as well as to measure the insulin-entrapment and drug-loading efficiencies. The in vitro release profile was obtained, and in vivo hypoglycemic effects were evaluated in streptozotocin-induced diabetic rats. Results Our results indicated that insulin-containing L/C NPs had a mean size of 180 nm, an insulin-entrapment efficiency of 94%, and an insulin-loading efficiency of 4.5%. Cryogenic transmission electron microscopy observations of insulin-loaded L/C NPs revealed multilamellar structures with a hollow core, encircled by several bilayers. In vitro analysis revealed that insulin release from L/C NPs depended on the L/C ratio. Insulin-loaded L/C NPs orally administered to streptozotocin-induced diabetic rats exerted a significant hypoglycemic effect. The relative pharmacological bioavailability following oral administration of L/C NPs was 6.01%. Conclusion With the aid of phospholipid-complexation techniques, some hydrophilic peptides, such as insulin, can be successfully entrapped into L/C NPs, which could improve oral bioavailability, time-dependent release, and therapeutic activity. PMID:26966360

  15. Characterization and Oral Delivery of Proinsulin-Transferrin Fusion Protein Expressed Using ExpressTec

    Directory of Open Access Journals (Sweden)

    Yu-Sheng Chen

    2018-01-01

    Full Text Available Proinsulin-transferrin fusion protein (ProINS-Tf has been designed and successfully expressed from the mammalian HEK293 cells (HEK-ProINS-Tf. It was found that HEK-ProINS-Tf could be converted into an activated form in the liver. Furthermore, HEK-ProINS-Tf was demonstrated as an extra-long acting insulin analogue with liver-specific insulin action in streptozotocin (STZ-induced type 1 diabetic mice. However, due to the low production yield from transfected HEK293 cells, there are other interesting features, including the oral bioavailability, which have not been fully explored and characterized. To improve the protein production yield, an alternative protein expression system, ExpressTec using transgenic rice (Oryza sativa L., was used. The intact and active rice-derived ProINS-Tf (ExpressTec-ProINS-Tf was successfully expressed from the transgenic rice expression system. Our results suggested that, although the insulin-like bioactivity of ExpressTec-ProINS-Tf was slightly lower in vitro, its potency of in vivo blood glucose control was considerably stronger than that of HEK-ProINS-Tf. The oral delivery studies in type 1 diabetic mice demonstrated a prolonged control of blood glucose to near-normal levels after oral administration of ExpressTec-ProINS-Tf. Results in this report suggest that ExpressTec-ProINS-Tf is a promising insulin analog with advantages including low cost, prolonged and liver targeting effects, and most importantly, oral bioactivity.

  16. Nanostructured lipid carriers used for oral delivery of oridonin: an effect of ligand modification on absorption.

    Science.gov (United States)

    Zhou, Xiaotong; Zhang, Xingwang; Ye, Yanghuan; Zhang, Tianpeng; Wang, Huan; Ma, Zhiguo; Wu, Baojian

    2015-02-20

    Oridonin (Ori) is a natural compound with notable anti-inflammation and anti-cancer activities. However, therapeutic use of this compound is limited by its poor solubility and low bioavailability. Here a novel biotin-modified nanostructured lipid carrier (NLC) was developed to enhance the bioavailability of Ori. The effect of ligand (biotin) modification on oral absorption of Ori encapsulated in NLCs was also explored. Ori-loaded NLCs (Ori-NLCs) were prepared by the melt dispersion-high pressure homogenization method. Biotin modification of Ori-NLCs was achieved by EDC and NHS in aqueous phase. The obtained biotin-decorated Ori-NLCs (Bio-Ori-NLCs) were 144.9nm in size with an entrapment efficiency of 49.54% and a drug load of 4.81%. Oral bioavailability was enhanced by use of Bio-Ori-NLCs with a relative bioavailability of 171.01%, while the value of non-modified Ori-NLCs was improved to 143.48%. Intestinal perfusion showed that Ori solution unexpectedly exhibited a moderate permeability, indicating that permeability was not a limiting factor of Ori absorption. Ori could be rapidly metabolized that was the main cause of low bioavailability. However, there was a difference in the enhancement of bioavailability between Bio-Ori-NLCs and conventional NLCs. Although severe lipolyses happened both on Bio-Ori-NLCs and non-modified NLCs, the performance of Bio-Ori-NLCs in the bioavailability improvement was more significant. Overall, Bio-Ori-NLCs can further promote the oral absorption of Ori by a ligand-mediated active transport. It may be a promising carrier for the oral delivery of Ori. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Poly methacrylic acid modified CDHA nanocomposites as potential pH responsive drug delivery vehicles.

    Science.gov (United States)

    Victor, Sunita Prem; Sharma, Chandra P

    2013-08-01

    The objective of this study was to prepare pH sensitive polymethacrylic acid-calcium deficient hydroxyapatite (CDHA) nanocomposites. The CDHA nanoparticles were prepared by coprecipitation method. The modification of CDHA by methacrylic acid (MA) was achieved by AIBN initiated free radical polymerization with sodium bisulphite as catalyst followed by emulsion technique. These nanocomposites with a half life of 8h consisted of high aspect ratio, needle like particles and exhibited an increase in swelling behaviour with pH. The in vivo potential of the nanocomposites was evaluated in vitro by the results of cell aggregation, protein adsorption, MTT assay and haemolytic activity. The invitro loading and release studies using albumin as a model drug indicate that the nanocomposites gave better loading when compared to the CDHA nanoparticles and altered the drug release rates. The nanocomposites also exhibited good uptake on C6 glioma cells as studied by fluorescence microscopy. The results obtained suggest that these nanocomposites have great potential for oral controlled protein delivery and can be extended further for intracellular drug delivery applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Noninvasive ocular drug delivery: potential transcorneal and other alternative delivery routes for therapeutic molecules in glaucoma.

    Science.gov (United States)

    Foldvari, Marianna

    2014-01-01

    Drug delivery to the eye is made difficult by multiple barriers (such as the tear film, cornea, and vitreous) between the surface of the eye and the treatment site. These barriers are difficult to surmount for the purposes of drug delivery without causing toxicity. Using nanotechnology tools to control, manipulate, and study delivery systems, new approaches to delivering drugs, genes, and antigens that are effective and safe can be developed. Topical administration to the ocular surface would be the safest method for delivery, as it is noninvasive and painless compared with other delivery methods. However, there is only limited success using topical delivery methods, especially for gene therapy. Current thinking on treatments of the future enabled by nanodelivery systems and the identification of target specificity parameters that require deeper understanding to develop successful topical delivery systems for glaucoma is highlighted.

  19. Receptor-mediated oral delivery of a bioencapsulated green fluorescent protein expressed in transgenic chloroplasts into the mouse circulatory system.

    Science.gov (United States)

    Limaye, Arati; Koya, Vijay; Samsam, Mohtashem; Daniell, Henry

    2006-05-01

    Oral delivery of biopharmaceutical proteins expressed in plant cells should reduce their cost of production, purification, processing, cold storage, transportation, and delivery. However, poor intestinal absorption of intact proteins is a major challenge. To overcome this limitation, we investigate here the concept of receptor-mediated oral delivery of chloroplast-expressed foreign proteins. Therefore, the transmucosal carrier cholera toxin B-subunit and green fluorescent protein (CTB-GFP), separated by a furin cleavage site, was expressed via the tobacco chloroplast genome. Polymerase chain reaction (PCR) and Southern blot analyses confirmed site-specific transgene integration and homoplasmy. Immunoblot analysis and ELISA confirmed expression of monomeric and pentameric forms of CTB-GFP, up to 21.3% of total soluble proteins. An in vitro furin cleavage assay confirmed integrity of the engineered furin cleavage site, and a GM1 binding assay confirmed the functionality of CTB-GFP pentamers. Following oral administration of CTB-GFP expressing leaf material to mice, GFP was observed in the mice intestinal mucosa, liver, and spleen in fluorescence and immunohistochemical studies, while CTB remained in the intestinal cell. This report of receptor-mediated oral delivery of a foreign protein into the circulatory system opens the door for low-cost production and delivery of human therapeutic proteins.

  20. Biodegradable nanoparticles loaded with insulin-phospholipid complex for oral delivery: preparation, in vitro characterization and in vivo evaluation.

    Science.gov (United States)

    Cui, Fude; Shi, Kai; Zhang, Liqiang; Tao, Anjin; Kawashima, Yoshiaki

    2006-08-28

    Biodegradable nanoparticles loaded with insulin-phospholipid complex were prepared by a novel reverse micelle-solvent evaporation method, in which soybean phosphatidylcholine (SPC) was employed to improve the liposolubility of insulin, and biodegradable polymers as carrier materials to control drug release. Solubilization study, IR and X-ray diffraction analysis were employed to prove the complex formation. The effects of key parameters such as polymer/SPC weight ratio, organic phase and polymer type on the properties of the nanoparticles were investigated. Spherical particles of 200 nm mean diameter and a narrow size distribution were obtained under optimal conditions. The drug entrapment efficiency was up to 90%. The in vitro drug release was characterized by an initial burst and subsequent delayed release in both pH 6.8 and pH 1.2 dissolution mediums. The specific modality of drug release, i.e., free or SPC-combined, was investigated in the aid of ultracentrifugation and ultrafiltration methods. The influence of polymer type on the drug release was also discussed. The pharmacological effects of the nanoparticles made of PLGA 50/50 (Av.Mw 9500) were further evaluated to confirm their potential suitability for oral delivery. Intragastric administration of the 20 IU/kg nanoparticles reduced fasting plasma glucose levels to 57.4% within the first 8 h of administration and this continued for 12 h. PK/PD analysis indicated that 7.7% of oral bioavailability relative to subcutaneous injection was obtained.

  1. Preparation and characterization of tetrandrine-phospholipid complex loaded lipid nanocapsules as potential oral carriers

    Directory of Open Access Journals (Sweden)

    Zhao YQ

    2013-10-01

    that the crystalline state was less ordered in lipid nanocapsules. The in vitro release study demonstrated a fast release of approximately 25% in the first 1 hour, which was followed by a sustained release of 70% over 12 hours. The relative bioavailability of TPC-LNCs compared to that of tablets was 208%, indicating a significant improvement in the oral absorption of tetrandrine.Conclusion: The TPC-LNCs system developed in this study is a promising carrier that improves the oral bioavailability of tetrandrine in rats. The phospholipid complex loaded lipid nanocapsules have great potential for use as an oral drug delivery system for moderately lipophilic drugs that are encapsulated in the lipid nanocapsules.Keywords: tetrandrine, phospholipid complex, lipid nanocapsules, oral bioavailability, enhanced liposolubility

  2. Poly(ethylene glycol) grafted chitosan as new copolymer material for oral delivery of insulin

    International Nuclear Information System (INIS)

    Ho, Thanh Ha; Thanh Le, Thi Nu; Nguyen, Tuan Anh; Dang, Mau Chien

    2015-01-01

    A new scheme of grafting poly (ethylene glycol) onto chitosan was proposed in this study to give new material for delivery of insulin over oral pathway. First, methoxy poly(ethylene glycol) amine (mPEGa MW 2000) were grafted onto chitosan (CS) through multiples steps to synthesize the grafting copolymer PEG-g-CS. After each synthesis step, chitosan and its derivatives were characterized by FTIR, "1H NMR Then, insulin loaded PEG-g-CS nanoparticles were prepared by cross-linking of CS with sodium tripolyphosphate (TPP). Same insulin loaded nanoparticles using unmodified chitosan were also prepared in order to compare with the modified ones. Results showed better protecting capacity of the synthesized copolymer over original CS. CS nanoparticles (10 nm of size) were gel like and high sensible to temperature as well as acidic environment while PEG-g-CS nanoparticles (200 nm of size) were rigid and more thermo and pH stable. (paper)

  3. Innovative Models of Dental Care Delivery and Coverage: Patient-Centric Dental Benefits Based on Digital Oral Health Risk Assessment.

    Science.gov (United States)

    Martin, John; Mills, Shannon; Foley, Mary E

    2018-04-01

    Innovative models of dental care delivery and coverage are emerging across oral health care systems causing changes to treatment and benefit plans. A novel addition to these models is digital risk assessment, which offers a promising new approach that incorporates the use of a cloud-based technology platform to assess an individual patient's risk for oral disease. Risk assessment changes treatment by including risk as a modifier of treatment and as a determinant of preventive services. Benefit plans are being developed to use risk assessment to predetermine preventive benefits for patients identified at elevated risk for oral disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Thiolated Eudragit nanoparticles for oral insulin delivery: preparation, characterization and in vivo evaluation.

    Science.gov (United States)

    Zhang, Yan; Wu, Xiaorong; Meng, Lingkuo; Zhang, Yu; Ai, Ruiting; Qi, Na; He, Haibing; Xu, Hui; Tang, Xing

    2012-10-15

    In the present study thiolated Eudragit L100 (Eul) based polymeric nanoparticles (NPs) were employed to develop an oral insulin delivery system. Sulfydryl modification was achieved by grafting cysteine to the carboxylic acid group of Eudragit L100, which displayed maximum conjugate level of 390.3±13.4 μmol thiol groups per gram. Eudragit L100-cysteine (Eul-cys) and Eul nanoparticles were prepared by the precipitation method, in which reversible swelling of pH-sensitive material was used for insulin loading and release. Nanoparticles were characterized in terms of their particle size, morphology, loading efficiency (LE%) and in vitro insulin release behavior. The NPs had an average size of 324.2±39.0 nm and 308.8±35.7 nm, maximal LE% of 92.2±1.7% and 96.4±0.5% for Eul-cys and Eul, respectively. The release profile of NPs in vitro showed pH-dependent behavior. Circular dichroism (CD) spectroscopy analysis proved that the secondary structure of the insulin released from NPs was unchanged compared with native insulin. The mucoadhesion study in vitro showed that Eul-cys NPs produced a 3-fold and 2.8-fold increase in rat jejunum and ileum compared with unmodified polymer NPs, respectively, which was due to the immobilization of thiol groups on Eudragit L100. Oral administration of insulin-loaded Eul-cys NPs produced a higher and prolonged hypoglycemic action, and the corresponding relative bioavailability of insulin was found to be 7.33±0.33%, an increase of 2.8-fold compared with Eul NPs (2.65±0.63%). This delivery system is a promising novel tool to improve the absorption of protein and peptide drugs in the intestinal tract. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Status of governmental oral health care delivery system in Haryana, India

    Directory of Open Access Journals (Sweden)

    Ashish Vashist

    2016-01-01

    Full Text Available Background: Health system should be organized to meet the needs of entire population of the nation. This means that the state has the direct responsibility for the health of its population and improving the quality of life through research, education, and provision of health services. The present study was conducted to evaluate the government oral health care delivery system in Haryana, India. Materials and Methods: The present cross-sectional study was conducted among 135 dental care units (DCUs of various primary health centers (PHCs, community health centers (CHCs, and general hospitals (GHs existing in the state by employing a cluster random sampling technique. Data regarding the provision of water and electricity supply, dental man power and their qualification, number and type of instruments in the dental operatory unit, etc., were collected on a structured format. Statistical analysis was done using number and percentages (SPSS package version 16. Results: Alternative source of electricity (generator existed in only a few of health centers. About 93.4% (155 of the staff were graduates (BDS and 6.6% (11 were postgraduates (MDS. Ultrasonic scaler was available at dental units of 83.1% (64 of PHCs, 73.1% (19 of CHCs, and 93.8% (30 of GHs. Patient drapes were provided in 48.1% (65 of the DCUs, doctor′s aprons were provided in 74.1% (100 of the places. Conclusion: There is a shortfall in infrastructure and significant problem with the adequacy of working facilities. A great deal of effort is required to harmonize the oral health care delivery system.

  6. A Novel Self-Microemulsifying System for the Simultaneous Delivery and Enhanced Oral Absorption of Curcumin and Resveratrol.

    Science.gov (United States)

    Jaisamut, Patcharawalai; Wiwattanawongsa, Kamonthip; Wiwattanapatapee, Ruedeekorn

    2017-03-01

    The use of curcumin and resveratrol in combination has now become increasingly of interest because of their synergistic effects as therapeutic agents for various diseases, especially cancer. To overcome the poor oral bioavailability of both compounds and improve patient compliance, a novel self-microemulsifying formulation containing curcumin together with resveratrol was developed. Capryol 90, Cremophor EL, and Labrasol were selected as the oil, surfactant, and co-surfactant in the formulation, respectively, based on the solubility study of both compounds. More than 70 % and 80 % of curcumin and resveratrol, respectively, were released in 20 min. The formulation formed a fine oil in water microemulsion with droplet sizes in aqueous media of 15-20 nm. In addition, the formulation containing curcumin and resveratrol showed greater antioxidant activity than that of the formulations with individual compounds, while the cytotoxic activity against HT-29 of the co-formulation (IC 50  = 18.25 µM; curcumin and resveratrol in the ratio 1 : 1) was less than the formulation with only curcumin (IC 50  = 30.1 µM) and only resveratrol (IC 50  = 25.4 µM). After oral administration to rabbits, the self-microemulsifying formulation containing curcumin together with resveratrol increased the total plasma concentrations of curcumin and resveratrol by 10-fold and 6-fold, respectively, compared to the unformulated combination. This study clearly demonstrated the potential use of the self-microemulsifying formulation for co-delivery, and enhanced oral absorption of poorly water-soluble natural compounds. In addition, the combination was found to produce synergistic antioxidant activity and cytotoxicity against HT-29 cells. Georg Thieme Verlag KG Stuttgart · New York.

  7. Core–shell hybrid nanocapsules for oral delivery of camptothecin: formulation development, in vitro and in vivo evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Ünal, Hale, E-mail: unalhale@gmail.com [Hacettepe University, Division of Nanotechnology and Nanomedicine, Institute of Pure and Applied Science (Turkey); D’Angelo, Ivana [Second University of Napoli, Di.S.T.A.Bi.F. (Italy); Pagano, Ester; Borrelli, Francesca; Izzo, Angelo; Ungaro, Francesca; Quaglia, Fabiana [University of Naples Federico II, Department of Pharmacy (Italy); Bilensoy, Erem [Hacettepe University, Division of Nanotechnology and Nanomedicine, Institute of Pure and Applied Science (Turkey)

    2015-01-15

    The objective of this study was to design and in vitro–in vivo evaluate oral nanocapsules prepared from amphiphilic cyclodextrins (CDs) or poly-ε-caprolactone (PCL) for the effective oral delivery of an anticancer agent, camptothecin (CPT). CPT-loaded anionic and Chitosan (CS)-coated cationic nanocapsules were prepared and characterized in vitro. Morphological analysis was performed by scanning electron microscope (SEM). CPT release profile was evaluated using dialysis method under sink conditions. To determine the protective effect and drug stability provided by nanocapsules, all the formulations were incubated in simulated gastrointestinal media. Measurement of mucoadhesive tendency of CPT-loaded nanocapsules was realized by turbidimetric method. Penetration of nanocapsules was performed through an artificial mucus model. The permeability of CPT in solution form and bound to nanocapsule formulations were demonstrated across Caco-2 cell line. Finally, the intestinal uptake of nanocapsules was evaluated in vivo, in a mouse model. Both anionic and cationic formulations were in the range of 180–220 nm with a narrow size distribution and desired zeta potential values. CPT-loaded nanocapsules were found to be stable in simulated gastrointestinal media. Turbidimetric measurements confirmed the interaction between nanoparticles and mucin. Penetration of CPT through an artificial mucus gel layer was higher with CS-coated nanocapsules in accordance with the results obtained from permeability studies across Caco-2 cell line. In vivo animal studies confirmed that the intestinal uptake of nanocapsules was significantly higher with cationic nanocapsules. CPT-loaded positively charged CD nanocapsules might be an attractive and promising treatment for oral chemotherapy.

  8. Core–shell hybrid nanocapsules for oral delivery of camptothecin: formulation development, in vitro and in vivo evaluation

    International Nuclear Information System (INIS)

    Ünal, Hale; D’Angelo, Ivana; Pagano, Ester; Borrelli, Francesca; Izzo, Angelo; Ungaro, Francesca; Quaglia, Fabiana; Bilensoy, Erem

    2015-01-01

    The objective of this study was to design and in vitro–in vivo evaluate oral nanocapsules prepared from amphiphilic cyclodextrins (CDs) or poly-ε-caprolactone (PCL) for the effective oral delivery of an anticancer agent, camptothecin (CPT). CPT-loaded anionic and Chitosan (CS)-coated cationic nanocapsules were prepared and characterized in vitro. Morphological analysis was performed by scanning electron microscope (SEM). CPT release profile was evaluated using dialysis method under sink conditions. To determine the protective effect and drug stability provided by nanocapsules, all the formulations were incubated in simulated gastrointestinal media. Measurement of mucoadhesive tendency of CPT-loaded nanocapsules was realized by turbidimetric method. Penetration of nanocapsules was performed through an artificial mucus model. The permeability of CPT in solution form and bound to nanocapsule formulations were demonstrated across Caco-2 cell line. Finally, the intestinal uptake of nanocapsules was evaluated in vivo, in a mouse model. Both anionic and cationic formulations were in the range of 180–220 nm with a narrow size distribution and desired zeta potential values. CPT-loaded nanocapsules were found to be stable in simulated gastrointestinal media. Turbidimetric measurements confirmed the interaction between nanoparticles and mucin. Penetration of CPT through an artificial mucus gel layer was higher with CS-coated nanocapsules in accordance with the results obtained from permeability studies across Caco-2 cell line. In vivo animal studies confirmed that the intestinal uptake of nanocapsules was significantly higher with cationic nanocapsules. CPT-loaded positively charged CD nanocapsules might be an attractive and promising treatment for oral chemotherapy

  9. Insulin Inclusion into a Tragacanth Hydrogel: An Oral Delivery System for Insulin

    OpenAIRE

    Mokhamad Nur; Todor Vasiljevic

    2018-01-01

    Nanoparticles or microparticles created by physical complexation between two polyelectrolytes may have a prospective use as an excipient for oral insulin administration. Natural polymers such as tragacanth, alginate, dextran, pullulan, hyaluronic acid, gelatin and chitosan can be potential candidates for this purpose. In this research, insulin particles were prepared by the inclusion of insulin into a tragacanth hydrogel. The effect of the pH and concentration relationship involving polyelect...

  10. An oral oligonucleotide delivery system based on a thiolated polymer: Development and in vitro evaluation.

    Science.gov (United States)

    Martien, Ronny; Hoyer, Herbert; Perera, Glen; Schnürch, Andreas Bernkop

    2011-08-01

    The purpose of this study was to develop and evaluate an oral oligonucleotide delivery system based on a thiolated polymer/reduced glutathione (GSH) system providing a protective effect toward nucleases and permeation enhancement. A polycarbophil-cysteine conjugate (PCP-Cys) was synthesized. Enzymatic degradation of a model oligonucleotide by DNase I and within freshly collected intestinal fluid was investigated in the absence and presence of PCP-Cys. Permeation studies with PCP-Cys/GSH versus control were performed in vitro on Caco-2 cell monolayers and ex vivo on rat intestinal mucosa. PCP-Cys displayed 223 ± 13.8 μmol thiol groups per gram polymer. After 4h, 61% of the free oligonucleotides were degraded by DNase I and 80% within intestinal fluid. In contrast, less than 41% (DNase I) and 60% (intestinal fluid) were degraded in the presence of 0.02% (m/v) PCP-Cys. Permeation studies revealed an 8-fold (Caco-2) and 10-fold (intestinal mucosa) increase in apparent permeability compared to buffer control. Hence, this PCP-Cys/GSH system might be a promising tool for the oral administration of oligonucleotides as it allows a significant protection toward degrading enzymes and facilitates their transport across intestinal membranes. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Preparation and characterization of docetaxel self-nanoemulsifying powders (SNEPs): A strategy for improved oral delivery

    Energy Technology Data Exchange (ETDEWEB)

    Sunkavalli, Sharath; Eedara, Basanth Babu; Janga, Karthik Yadav; Velpula, Ashok; Jukanti, Raju; Bandari, Suresh [St. Peter' s Institute of Pharmaceutical Sciences, Warangal (India)

    2016-03-15

    Liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) of docetaxel were prepared using varying ratios of Capmul PG 8 NF (oil), Cremophor EL (surfactant) and Transcutol-P (co-surfactant). The optimized L-SNEDDS (L{sub 11}) was transformed into self-nanoemulsifying powder (SNEP) by physical adsorption on to Neusilin US2 and evaluated for dissolution behavior, in vitro cytotoxicity and in vivo oral bioavailability. Optimized L-SNEDDS (L{sub 11}) composed of 50% of oil, 41.7% of surfactant and 8.3% co-surfactant produced stable emulsion with smaller globules (43±3 nm). In vitro dissolution studies showed the rapid drug release within 5min (95.42±1%) from SNEP{sub N}. In vitro cytotoxicity assessed by the MTT assay using MCF-7 human breast cancer cell lines revealed that L-SNEDDS significantly reduced the IC{sub 50} value and was 2.3 times lower than the pure docetaxel. Further, the oral bioavailability studies in male Wistar rats showed higher C{sub max} values following treatment with SNEP{sub N} (0.98±0.13 μg/mL) and L-SNEDDS (1.09± 0.06 μg/mL) compared to pure docetaxel (0.37±0.04 μg/mL).

  12. Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery.

    Science.gov (United States)

    Sadekar, S; Ghandehari, H

    2012-05-01

    This article summarizes efforts to evaluate poly(amido amine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the effect of PAMAM generation, surface charge and surface modification on toxicity, cellular uptake and transepithelial transport is discussed. Studies on Caco-2 monolayers, as models of intestinal epithelial barrier, show that by engineering surface chemistry of PAMAM dendrimers, it is possible to minimize toxicity while maximizing transepithelial transport. It has been demonstrated that PAMAM dendrimers are transported by a combination of paracellular and transcellular routes. Depending on surface chemistry, PAMAM dendrimers can open the tight junctions of epithelial barriers. This tight junction opening is in part mediated by internalization of the dendrimers. Transcellular transport of PAMAM dendrimers is mediated by a variety of endocytic mechanisms. Attachment or complexation of cytotoxic agents to PAMAM dendrimers enhances the transport of such drugs across epithelial barriers. A remaining challenge is the design and development of linker chemistries that are stable in the gastrointestinal tract (GIT) and the blood stream, but amenable to cleavage at the target site of action. Recent efforts have focused on the use of PAMAM dendrimers as penetration enhancers. Detailed in vivo oral bioavailability of PAMAM dendrimer-drug conjugates, as a function of physicochemical properties will further need to be assessed. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Influence of Electron Irradiation Factor on Haruan Traditional Extract (HTE) for Oral Drug Delivery

    International Nuclear Information System (INIS)

    Ibrahim Ijang; Abdul Manan, M.J.; Kamaruddin Hashim

    2014-01-01

    Haruan or Channa striatus is source of protein, Haruan extract is well known in the region for having a medicinal quality and widely consumed. It is great advantage if this product could be administered by oral rather than injection because oral route of drug delivery is still preferred by the vast majority of patients. However protein and peptides can be denatured or degraded by conditions included the acidic pH of the stomach and presence of endogenous enzymes. In order to protect or prevent digestion and degradation of the protein in the stomach and to ensure the protein reach to gastro intestinal (GI) tract, CMS nano gel system was developed using electron irradiation method. However stability of HTE toward radiation needed to be ensured before being used for the next level. In this study, the HTE was radiated with electron radiation. Its stability was analysed in term of physical aspect by looking at the colour difference, melting point by using Differential Scanning Calorimetry (DSC) and in terms of chemical aspect which include molecular bonds by using Fourier Transform Infrared (FTIR). The results of this study were that no apparent colour difference was seen on the HTE before and after irradiation. Those are supported by FTIR and DSC analysis results that showed that there were no change of molecular bonds and melting point, compared between no irradiation and irradiation HTE during electron irradiation up to 10 kGy. Statistically the test showed no significant difference at p<0.005 within melting temperatures. (author)

  14. Influence of Electron Beam Irradiation on Peptide of Haruan Traditional Extract (HTE) for Oral Drug Delivery

    International Nuclear Information System (INIS)

    Ibrahim Ijang

    2015-01-01

    Haruan or Channa striatus is source of protein, Haruan extract is well known in the region for having a medicinal quality and widely consumed. It is great advantage if this product could be administered by oral rather than injection because oral route of drug delivery is still preferred by the vast majority of patients. However protein and peptides can be denatured or degraded by conditions included the acidic pH of the stomach and presence of endogenous enzymes. In order to protect or prevent digestion and degradation of the protein in the stomach and to ensure the protein reach to gastro intestinal (GI) tract, CMS nano gel system was developed using electron irradiation method. However stability of HTE toward radiation needed to be ensured before being used for the next level. In this study, the HTE was radiated with electron radiation. Its stability was analysed in term of physical aspect by looking at the colour difference, melting point by using Differential Scanning Calorimetry (DSC) and in terms of chemical aspect which include molecular bonds by using Fourier Transform Infrared (FTIR). The results of this study were that no apparent colour difference was seen on the HTE before and after irradiation. Those are supported by FTIR and DSC analysis results that showed that there were no change of molecular bonds and melting point, compared between no irradiation and irradiation HTE during electron irradiation up to 30 KGy. Statistically the test showed no significant difference at p<0.005 within melting temperatures. (author)

  15. Evaluation of AgNORs in Oral Potentially Malignant Lesions

    Directory of Open Access Journals (Sweden)

    Karin Berria Tomazelli

    2015-01-01

    Full Text Available Oral squamous cell carcinoma (OSCC is usually preceded by detectable mucosal changes, as leukoplakias and erythroplakia. Histologically, these lesions can range from hyperkeratosis and acanthosis to epithelial dysplasia and even OSCC. The aim of this study was to investigate the proliferative activity, using AgNORs quantification proteins, in low- and high-risk oral epithelial dysplasia, OSCC, and nondysplastic epithelium (inflammatory fibrous hyperplasia. The sample was divided into 4 groups: G1: 10 cases of inflammatory fibrous hyperplasia (IFH, G2: 11 cases of low-risk epithelial dysplasia (LD, G3: 10 cases of high-risk epithelial dysplasia (HD, and G4: 11 cases of OSCC. The quantitative analysis was performed using an image processing software in photomicrographs at 1000x magnification. The one-way ANOVA was used for comparison of the mean AgNORs counts between the study groups. The mean AgNORs count was significantly higher P≤0.01 in OSCC when compared to IFH and the LD; however, it was not statistically different from HD. The mean number of LD was significantly lower than the HD and OSCC, with no difference related to IFH. AgNORs quantification can be an important and cheap method to help in the determination of the degree of epithelial dysplasia and, consequently, in the analysis of their potential for malignant transformation.

  16. Assessing the contribution of the dental care delivery system to oral health care disparities.

    Science.gov (United States)

    Pourat, Nadereh; Andersen, Ronald M; Marcus, Marvin

    2015-01-01

    Existing studies of disparities in access to oral health care for underserved populations often focus on supply measures such as number of dentists. This approach overlooks the importance of other aspects of the dental care delivery system, such as personal and practice characteristics of dentists, that determine the capacity to provide care. This study aims to assess the role of such characteristics in access to care of underserved populations. We merged data from the 2003 California Health Interview Survey and a 2003 survey of California dentists in their Medical Study Service Areas (MSSAs). We examined the role of overall supply and other characteristics of dentists in income and racial/ethnic disparities in access, which was measured by annual dental visits and unmet need for dental care due to costs. We found that some characteristics of MSSAs, including higher proportions of dentists who were older, white, busy or overworked, and did not accept public insurance or discounted fees, inhibited access for low-income and minority populations. These findings highlight the importance of monitoring characteristics of dentists in addition to traditional measures of supply such as licensed-dentist-to-population ratios. The findings identify specific aspects of the delivery system such as dentists' participation in Medicaid, provision of discounted care, busyness, age, race/ethnicity, and gender that should be regularly monitored. These data will provide a better understanding of how the dental care delivery system is organized and how this knowledge can be used to develop more narrowly targeted policies to alleviate disparities. © 2014 American Association of Public Health Dentistry.

  17. Colon-targeted oral drug delivery systems: design trends and approaches.

    Science.gov (United States)

    Amidon, Seth; Brown, Jack E; Dave, Vivek S

    2015-08-01

    Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS.

  18. In vivo evaluation of an oral drug delivery system for peptides based on S-protected thiolated chitosan.

    Science.gov (United States)

    Dünnhaupt, Sarah; Barthelmes, Jan; Iqbal, Javed; Perera, Glen; Thurner, Clemens C; Friedl, Heike; Bernkop-Schnürch, Andreas

    2012-06-28

    The aim of the present study was the development and evaluation in vitro as well as in vivo of an oral delivery system based on a novel type of thiolated chitosan, so-called S-protected thiolated chitosan, for the peptide drug antide. The sulfhydryl ligand thioglycolic acid (TGA) was covalently attached to chitosan (CS) in the first step of modification. In the second step, these thiol groups of thiolated chitosan were protected by disulfide bond formation with the thiolated aromatic residue 6-mercaptonicotinamide (6-MNA). Absorptive transport studies of antide were evaluated ex vivo using rat intestinal mucosa. Matrix tablets of each polymer sample were prepared and their effect on the absorption of antide evaluated in vivo in male Sprague-Dawley rats. In addition, tablets were examined in terms of their disintegration, swelling and drug release behavior. The resulting S-protected thiomer (TGA-MNA) exhibited 840μmol of covalently linked 6-MNA per gram thiomer. Based on the implementation of this hydrophobic ligand on the thiolated backbone, the disintegration behavior was reduced greatly and a controlled release of the peptide could be achieved. Furthermore, permeation studies with TGA-MNA on rat intestine revealed a 4.5-fold enhanced absorptive transport of the peptide in comparison to antide in solution. Additional in vivo studies confirmed the potential of this novel conjugate. Oral administration of antide in solution led to only very small detectable quantities in plasma with an absolute and relative bioavailability (BA) of 0.003 and 0.03%, only. In contrast, with antide incorporated in TGA-MNA matrix tablets an absolute and relative BA of 1.4 and 10.9% could be reached, resulting in a 421-fold increased area under the plasma concentration time curve (AUC) compared to the antide solution. According to these results, S-protected thiolated chitosan as oral drug delivery system might be a valuable tool for improving the bioavailability of peptides. Copyright

  19. Ficus Deltoidea: A potential source for new oral antidiabetic agent

    International Nuclear Information System (INIS)

    Zainah Adam; Juliana Mahamad Napiah; Shafii Khamis; Muhajir Hamid

    2012-01-01

    Ficus deltoidea or locally known as Mas Cotek is one of the common medicinal plant used in Malaysia. Ethno botanical approaches showed that this plant possess antidiabetic property. Previous study had shown that F. deltoidea reduced hyperglycemia in type I diabetic rats at different prandial state. This study was done to elucidate the possible antihyperglycemic mechanisms of F. deltoidea. The results showed that F. deltoidea significantly stimulated insulin secretion from pancreatic β-cells with the highest magnitude of stimulation was 7.31-fold (p 50 value was 4.15±0.25 mg/ml. Kinetic analysis of the enzyme activity revealed the F. deltoidea exhibited a mixed-type inhibition mechanism against sucrase activity. Such observations showed that F. deltoidea has the potential to be developed as new oral antidiabetic agent for the treatment of diabetes mellitus. (author)

  20. Oral Cholera Vaccination Delivery Cost in Low- and Middle-Income Countries: An Analysis Based on Systematic Review.

    Science.gov (United States)

    Mogasale, Vittal; Ramani, Enusa; Wee, Hyeseung; Kim, Jerome H

    2016-12-01

    Use of the oral cholera vaccine (OCV) is a vital short-term strategy to control cholera in endemic areas with poor water and sanitation infrastructure. Identifying, estimating, and categorizing the delivery costs of OCV campaigns are useful in analyzing cost-effectiveness, understanding vaccine affordability, and in planning and decision making by program managers and policy makers. To review and re-estimate oral cholera vaccination program costs and propose a new standardized categorization that can help in collation, analysis, and comparison of delivery costs across countries. Peer reviewed publications listed in PubMed database, Google Scholar and World Health Organization (WHO) websites and unpublished data from organizations involved in oral cholera vaccination. The publications and reports containing oral cholera vaccination delivery costs, conducted in low- and middle-income countries based on World Bank Classification. Limits are humans and publication date before December 31st, 2014. No participants are involved, only costs are collected. Oral cholera vaccination and cost estimation. A systematic review was conducted using pre-defined inclusion and exclusion criteria. Cost items were categorized into four main cost groups: vaccination program preparation, vaccine administration, adverse events following immunization and vaccine procurement; the first three groups constituting the vaccine delivery costs. The costs were re-estimated in 2014 US dollars (US$) and in international dollar (I$). Ten studies were identified and included in the analysis. The vaccine delivery costs ranged from US$0.36 to US$ 6.32 (in US$2014) which was equivalent to I$ 0.99 to I$ 16.81 (in I$2014). The vaccine procurement costs ranged from US$ 0.29 to US$ 29.70 (in US$2014), which was equivalent to I$ 0.72 to I$ 78.96 (in I$2014). The delivery costs in routine immunization systems were lowest from US$ 0.36 (in US$2014) equivalent to I$ 0.99 (in I$2014). The reported cost categories

  1. Oral Cholera Vaccination Delivery Cost in Low- and Middle-Income Countries: An Analysis Based on Systematic Review

    Science.gov (United States)

    Ramani, Enusa; Wee, Hyeseung; Kim, Jerome H.

    2016-01-01

    Background Use of the oral cholera vaccine (OCV) is a vital short-term strategy to control cholera in endemic areas with poor water and sanitation infrastructure. Identifying, estimating, and categorizing the delivery costs of OCV campaigns are useful in analyzing cost-effectiveness, understanding vaccine affordability, and in planning and decision making by program managers and policy makers. Objectives To review and re-estimate oral cholera vaccination program costs and propose a new standardized categorization that can help in collation, analysis, and comparison of delivery costs across countries. Data sources Peer reviewed publications listed in PubMed database, Google Scholar and World Health Organization (WHO) websites and unpublished data from organizations involved in oral cholera vaccination. Study eligibility criteria The publications and reports containing oral cholera vaccination delivery costs, conducted in low- and middle-income countries based on World Bank Classification. Limits are humans and publication date before December 31st, 2014. Participants No participants are involved, only costs are collected. Intervention Oral cholera vaccination and cost estimation. Study appraisal and synthesis method A systematic review was conducted using pre-defined inclusion and exclusion criteria. Cost items were categorized into four main cost groups: vaccination program preparation, vaccine administration, adverse events following immunization and vaccine procurement; the first three groups constituting the vaccine delivery costs. The costs were re-estimated in 2014 US dollars (US$) and in international dollar (I$). Results Ten studies were identified and included in the analysis. The vaccine delivery costs ranged from US$0.36 to US$ 6.32 (in US$2014) which was equivalent to I$ 0.99 to I$ 16.81 (in I$2014). The vaccine procurement costs ranged from US$ 0.29 to US$ 29.70 (in US$2014), which was equivalent to I$ 0.72 to I$ 78.96 (in I$2014). The delivery costs in

  2. Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

    Science.gov (United States)

    Dhote, Vinod; Bhatnagar, Punit; Mishra, Pradyumna K.; Mahajan, Suresh C.; Mishra, Dinesh K.

    2012-01-01

    The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application. PMID:22396901

  3. Potential of Piper betle extracts on inhibition of oral pathogens.

    Science.gov (United States)

    Phumat, Pimpak; Khongkhunthian, Sakornrat; Wanachantararak, Phenphichar; Okonogi, Siriporn

    2017-01-01

    In the present study, antimicrobial activity of Piper betle crude ethanol extract against 4 strains of oral pathogens; Candida albicans DMST 8684, C. albicans DMST 5815, Streptococcus gordonii DMST 38731 and Streptococcus mutans DMST 18777 was compared with other medicinal plants. P. betle showed the strongest antimicrobial activity against all tested strains. Fractionated extracts of P. betle using hexane, ethyl acetate, and ethanol, respectively, were subjected to antimicrobial assay. The result revealed that the fractionated extract from ethyl acetate (F-EtOAc) possessed the strongest antimicrobial activity against all tested strains. Its inhibition zones against those pathogens were 23.00 ± 0.00, 24.33 ± 0.58, 12.50 ± 0.70 and 11.00 ± 0.00 mm, respectively and its minimum inhibitory concentrations were 0.50, 1.00, 0.50 and 1.00 mg/mL, respectively. Interestingly, the minimum concentration to completely kill those pathogens was the same for all strains and found to be 2.00 mg/mL. Killing kinetic study revealed that the activity of F-EtOAc was dose dependent. HPLC chromatograms of P. betle extracts were compared with its antimicrobial activity. An obvious peak at a retention time of 4.11 min was found to be a major component of F-EtOAc whereas it was a minor compound in the other extracts. This peak was considered to be an active compound of P. betle as it was consistent with the antimicrobial activity of F-EtOAc, the most potential extract against the tested pathogens. It is suggested that F-EtOAc is a promising extract of P. betle for inhibition of oral pathogens. Separation and structure elucidation of the active compound of this extract will be further investigated.

  4. Facile preparation of pH-responsive polyurethane nanocarrier for oral delivery

    Energy Technology Data Exchange (ETDEWEB)

    Nabid, Mohammad Reza, E-mail: M-nabid@sbu.ac.ir; Omrani, Ismail

    2016-12-01

    This study reports a novel one pot synthesis of pH-responsive nanocarrier for oral delivery of hydrophobic drug under gastrointestinal tract. Triblock copolymer MPEG-HTPB-MPEG was synthesized coupling of MPEG and HTPB using hexamethylene diisocyanate(HDI) and pH-responsive carboxylic acid group was attached to polybuthadiene backbone by thiol-ene click reaction in a facile and convenient procedure. The MPEG-HTPB (g-COOH)-MPEG block copolymers were self-organized into micelle assemblies in the water. The size and shape of the micelle assemblies were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The nanocarriers have high drug loading ability for poorly water-soluble drug. The pH-responsive profile was demonstrated by pH-dependent swelling and in vitro drug release. < 10.0% IBU was released under artificial gastric fluid after 2 h, whereas an immediate release was observed under artificial intestinal fluid. The XTT assay indicated that the micelle obtained from PEG-HTPB (g-COOH)-PEG triblock copolymer are safe in a wide range of concentrations. The results show that pH-responsive PEG-HTPB (g-COOH)-PEG triblock copolymers are promising nanocarriers for the oral administration of hydrophobic drugs. - Highlights: • A facile method for synthesis of pH-responsive nanocarriers was developed. • pH-responsive amphiphilic polymer was synthesized using a rapid and one-pot procedure. • The nanocarriers have high drug loading ability for poorly water-soluble drug. • The nanocarriers show pH-dependent release profile. • The nanocarriers were stable in the gastric fluid and ruptured to release the loaded drug in intestinal fluid.

  5. Facile preparation of pH-responsive polyurethane nanocarrier for oral delivery

    International Nuclear Information System (INIS)

    Nabid, Mohammad Reza; Omrani, Ismail

    2016-01-01

    This study reports a novel one pot synthesis of pH-responsive nanocarrier for oral delivery of hydrophobic drug under gastrointestinal tract. Triblock copolymer MPEG-HTPB-MPEG was synthesized coupling of MPEG and HTPB using hexamethylene diisocyanate(HDI) and pH-responsive carboxylic acid group was attached to polybuthadiene backbone by thiol-ene click reaction in a facile and convenient procedure. The MPEG-HTPB (g-COOH)-MPEG block copolymers were self-organized into micelle assemblies in the water. The size and shape of the micelle assemblies were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The nanocarriers have high drug loading ability for poorly water-soluble drug. The pH-responsive profile was demonstrated by pH-dependent swelling and in vitro drug release. < 10.0% IBU was released under artificial gastric fluid after 2 h, whereas an immediate release was observed under artificial intestinal fluid. The XTT assay indicated that the micelle obtained from PEG-HTPB (g-COOH)-PEG triblock copolymer are safe in a wide range of concentrations. The results show that pH-responsive PEG-HTPB (g-COOH)-PEG triblock copolymers are promising nanocarriers for the oral administration of hydrophobic drugs. - Highlights: • A facile method for synthesis of pH-responsive nanocarriers was developed. • pH-responsive amphiphilic polymer was synthesized using a rapid and one-pot procedure. • The nanocarriers have high drug loading ability for poorly water-soluble drug. • The nanocarriers show pH-dependent release profile. • The nanocarriers were stable in the gastric fluid and ruptured to release the loaded drug in intestinal fluid.

  6. Preclinical Studies on Intestinal Administration of Antisense Oligonucleotides as a Model for Oral Delivery for Treatment of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Maaike van Putten

    2014-01-01

    Full Text Available Antisense oligonucleotides (AONs used to reframe dystrophin mRNA transcripts for Duchenne muscular dystrophy (DMD patients are tested in clinical trials. Here, AONs are administered subcutaneously and intravenously, while the less invasive oral route would be preferred. Oral delivery of encapsulated AONs supplemented with a permeation enhancer, sodium caprate, has been successfully used to target tumor necrosis factor (TNF-α expression in liver. To test the feasibility of orally delivered AONs for DMD, we applied 2′-O-methyl phosphorothioate AONs (with or without sodium caprate supplementation directly to the intestine of mdx mice and compared pharmacokinetics and -dynamics with intravenous, intraperitoneal, and subcutaneous delivery. Intestinally infused AONs were taken up, but resulted in lower plasma levels compared to other delivery routes, although bioavailability could be largely improved by supplementation of sodium caprate. After intestinal infusion, AON levels in all tissues were lower than for other administration routes, as were the ratios of target versus nontarget organ levels, except for diaphragm and heart where comparable levels and ratios were observed. For each administration route, low levels of exon skipping in triceps was observed 3 hours post-AON administration. These data suggest that oral administration of naked 2′-O-methyl phosphorothioate AONs may be feasible, but only when high AON concentrations are used in combination with sodium caprate.

  7. Development of hydrocortisone succinic acid/and 5-fluorouracil/chitosan microcapsules for oral and topical drug deliveries.

    Science.gov (United States)

    Lam, Pik-Ling; Lee, Kenneth Ka-Ho; Wong, Raymond Siu-Ming; Cheng, Gregory Yin Ming; Cheng, Shuk Yan; Yuen, Marcus Chun-Wah; Lam, Kim-Hung; Gambari, Roberto; Kok, Stanton Hon-Lung; Chui, Chung-Hin

    2012-05-01

    Recently, we demonstrated the safety use of calendula oil/chitosan microcapsules as a carrier for both oral and topical deliveries. We also reported the improved biological activity towards skin cells and Staphylococcus aureus of phyllanthin containing chitosan microcapsules. However, the possibility of both oral and topical applications was still necessary to be further studied. Here we investigated that both oral and topical applications of chitosan-based microcapsules were tested using hydrocortisone succinic acid (HSA) and 5-fluorouracil (5-FU), respectively. The drug loading efficiency, particle size, surface morphology and chemical compositions of both drug loaded microcapsules were confirmed by UV-vis spectrophotometer, particle size analyzer, scanning electron microscope and Fourier transform infrared spectroscopy. The in vitro release studies revealed that both HSA and 5-FU could be released form chitosan microcapsules. The mean adrenocorticotropic hormone concentration in HSA loaded microcapsule mice plasma was detected to be lower than that of water control. One hundred micrograms per milliliter of 5-FU containing microcapsules exhibited a stronger growth inhibition towards skin keratinocytes than that of free 5-FU. In vitro drug delivery model demonstrated the delivery of 5-FU from microcapsule treated textiles into nude mice skin. Further uses of the drug loaded microcapsules may provide an efficiency deliverable tool for both oral and topical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Salivary micro RNA as a potential biomarker in oral potentially malignant disorders: A systematic review

    Directory of Open Access Journals (Sweden)

    T N Uma Maheswari

    2018-01-01

    Full Text Available Oral potentially malignant disorders (OPMD are oral mucosal disorders which have a high potential to turn into malignancy. A recent report suggests that 16%–62% of epithelial dysplasia cases of OPMD undergo malignant transformation, showing the need for early detection of malignancy in these disorders. Micro RNA (miRNA plays an important role in cellular growth, differentiation, apoptosis, and immune response, and hence, deregulation of miRNA is considered a signature of oral carcinogenesis. A search was done using MeSH terms in the PubMed, ScienceDirect databases, hand search, and finally, six studies were included in this systematic review. A total of 167 patients with oral cancer, 78 with OPMDs, 147 healthy controls, and 20 disease controls were analyzed for the expression of salivary miRNAs. Quality assessment based on the Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to obtain a risk of bias chart using Revman 5.3 software and it was proved that the study done by Zahran et al. in 2015 had a low risk of bias. The results of this study revealed upregulated miRNA 184 with an area under the curve (AUC of 0.86 and miRNA 21 with an AUC of 0.73 and downregulated miRNA 145 with an AUC of 0.68, which proved that these miRNAs are significant in detecting early malignancy in OPMD and should be further analyzed in various populations. This systematic review explored the potential of expression of salivary miRNA in OPMD for future studies. This could pave the way to utilize saliva as a surrogate marker in diagnosing early malignant changes in OPMD.

  9. Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system

    Directory of Open Access Journals (Sweden)

    Chen ZQ

    2012-02-01

    Full Text Available Zhi-Qiang Chen, Ying Liu, Ji-Hui Zhao, Lan Wang, Nian-Ping FengSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of ChinaBackground: Indirubin, isolated from the leaves of the Chinese herb Isatis tinctoria L, is a protein kinase inhibitor and promising antitumor agent. However, the poor water solubility of indirubin has limited its application. In this study, a supersaturatable self-microemulsifying drug delivery system (S-SMEDDS was developed to improve the oral bioavailability of indirubin.Methods: A prototype S-SMEDDS was designed using solubility studies and phase diagram construction. Precipitation inhibitors were selected from hydrophilic polymers according to their crystallization-inhibiting capacity through in vitro precipitation tests. In vitro release of indirubin from S-SMEDDS was examined to investigate its likely release behavior in vivo. The in vivo bioavailability of indirubin from S-SMEDDS and from SMEDDS was compared in rats.Results: The prototype formulation of S-SMEDDS comprised Maisine™ 35-1:Cremophor® EL:Transcutol® P (15:40:45, w/w/w. Polyvinylpyrrolidone K17, a hydrophilic polymer, was used as a precipitation inhibitor based on its better crystallization-inhibiting capacity compared with polyethylene glycol 4000 and hydroxypropyl methylcellulose. In vitro release analysis showed more rapid drug release from S-SMEDDS than from SMEDDS. In vivo bioavailability analysis in rats indicated that improved oral absorption was achieved and that the relative bioavailability of S-SMEDDS was 129.5% compared with SMEDDS.Conclusion: The novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of indirubin in rats. The results suggest that S-SMEDDS is a superior means of oral delivery of indirubin.Keywords: supersaturatable self-microemulsifying drug delivery system, indirubin, bioavailability, oral drug delivery, hydrophilic polymer

  10. Oral delivery of Angiotensin-converting enzyme 2 and Angiotensin-(1-7) bioencapsulated in plant cells attenuates pulmonary hypertension.

    Science.gov (United States)

    Shenoy, Vinayak; Kwon, Kwang-Chul; Rathinasabapathy, Anandharajan; Lin, Shina; Jin, Guiying; Song, Chunjuan; Shil, Pollob; Nair, Anand; Qi, Yanfei; Li, Qiuhong; Francis, Joseph; Katovich, Michael J; Daniell, Henry; Raizada, Mohan K

    2014-12-01

    Emerging evidences indicate that diminished activity of the vasoprotective axis of the renin-angiotensin system, constituting angiotensin-converting enzyme 2 (ACE2) and its enzymatic product, angiotensin-(1-7) [Ang-(1-7)] contribute to the pathogenesis of pulmonary hypertension (PH). However, long-term repetitive delivery of ACE2 or Ang-(1-7) would require enhanced protein stability and ease of administration to improve patient compliance. Chloroplast expression of therapeutic proteins enables their bioencapsulation within plant cells to protect against gastric enzymatic degradation and facilitates long-term storage at room temperature. Besides, fusion to a transmucosal carrier helps effective systemic absorption from the intestine on oral delivery. We hypothesized that bioencapsulating ACE2 or Ang-(1-7) fused to the cholera nontoxin B subunit would enable development of an oral delivery system that is effective in treating PH. PH was induced in male Sprague Dawley rats by monocrotaline administration. Subset of animals was simultaneously treated with bioencapsulaed ACE2 or Ang-(1-7) (prevention protocol). In a separate set of experiments, drug treatment was initiated after 2 weeks of PH induction (reversal protocol). Oral feeding of rats with bioencapsulated ACE2 or Ang-(1-7) prevented the development of monocrotaline-induced PH and improved associated cardiopulmonary pathophysiology. Furthermore, in the reversal protocol, oral ACE2 or Ang-(1-7) treatment significantly arrested disease progression, along with improvement in right heart function, and decrease in pulmonary vessel wall thickness. In addition, a combination therapy with ACE2 and Ang-(1-7) augmented the beneficial effects against monocrotaline-induced lung injury. Our study provides proof-of-concept for a novel low-cost oral ACE2 or Ang-(1-7) delivery system using transplastomic technology for pulmonary disease therapeutics. © 2014 American Heart Association, Inc.

  11. Selenium nanoparticles: potential in cancer gene and drug delivery.

    Science.gov (United States)

    Maiyo, Fiona; Singh, Moganavelli

    2017-05-01

    In recent decades, colloidal selenium nanoparticles have emerged as exceptional selenium species with reported chemopreventative and therapeutic properties. This has sparked widespread interest in their use as a carrier of therapeutic agents with results displaying synergistic effects of selenium with its therapeutic cargo and improved anticancer activity. Functionalization remains a critical step in selenium nanoparticles' development for application in gene or drug delivery. In this review, we highlight recent developments in the synthesis and functionalization strategies of selenium nanoparticles used in cancer drug and gene delivery systems. We also provide an update of recent preclinical studies utilizing selenium nanoparticles in cancer therapeutics.

  12. Poly(n-butylcyanoacrylate nanoparticles for oral delivery of quercetin: preparation, characterization, and pharmacokinetics and biodistribution studies in Wistar rats

    Directory of Open Access Journals (Sweden)

    Bagad M

    2015-06-01

    Full Text Available Mayur Bagad, Zaved Ahmed KhanMedical Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore Tamil Nadu, IndiaBackground: Quercetin (QT is a potential bioflavonol and antioxidant with poor bioavailability and very low distribution in the brain. A new oral delivery system comprising of poly(n-butylcyanoacrylate nanoparticles (PBCA NPs was introduced to improve the oral bioavailability of QT and to increase its distribution in the brain. Physicochemical characteristics, in vitro release, stability in simulated gastric fluid and intestinal fluids, and pharmacokinetics and biodistribution studies of QT-PBCA NPs coated with polysorbate-80 (P-80 were investigated.Objective: This study aimed to investigate the physicochemical characteristics, in vitro release, stability in simulated gastric fluid and intestinal fluids, and pharmacokinetics and biodistribution studies of QT-PBCA NPs coated with polysorbate-80 (P-80.Results: The results showed that QT-PBCA NPs and QT-PBCA NPs coated with P-80 (QT-PBCA+P-80 had mean particle sizes of 161.1±0.44 nm and 166.6±0.33 nm respectively, and appeared spherical in shape under transmission electron microscopy. The mean entrapment efficiency was 79.86%±0.45% for QT-PBCA NPs and 74.58%±1.44% for QT-PBCA+P-80. The in vitro release of QT-PBCA NPs and QT-PBCA+P-80 showed an initial burst release followed by a sustained release when compared to free QT. The relative bioavailability of QT-PBCA NPs and QT-PBCA+P-80 enhanced QT bioavailability by 2.38- and 4.93-fold respectively, when compared to free QT. The biodistribution study in rats showed that a higher concentration of QT was detected in the brain after the NPs were coated with P-80.Conclusion: This study indicates that PBCA NPs coated with P-80 can be potential drug carriers for poorly water-soluble drugs. These NPs were observed to improve the drugs’ oral bioavailability and enhance their transport to the brain

  13. Expression of ABCG2 and Bmi-1 in oral potentially malignant lesions and oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Dalley, Andrew J; Pitty, Luke P; Major, Aidan G; AbdulMajeed, Ahmad A; Farah, Camile S

    2014-01-01

    Early diagnosis is vital for effective treatment of oral squamous cell carcinoma (OSCC). The optimal time for clinical intervention is prior to malignancy when patients present with oral potentially malignant lesions such as leukoplakia or erythroplakia. Transformation rates for oral dysplasia vary greatly and more rigorous methods are needed to predict the malignant potential of oral lesions. We hypothesized that the expression of two putative stem cell markers, ABCG2 and Bmi-1, would correlate with disease severity for non diseased, potentially malignant and OSCC specimens and cell lines derived from an equivalent range of tissues. We compared immunoreactive protein and relative gene expression of ABCG2 and Bmi-1 in eight cell lines derived from source tissues ranging in disease severity from normal (OKF6-TERT2) through mild and moderate/severe dysplasia (DOK, POE-9n) to OSCC (PE/CA-PJ15, SCC04, SCC25, SCC09, SCC15). We also analyzed immunoreactive protein expression of ABCG2 and Bmi-1 in 189 tissue samples with the same range of disease severity. A trend between oral lesion severity to ABCG2 and Bmi-1 immunostain intensity was observed. Flow cytometry of oral cell lines confirmed this trend and gave good correlation with RT-PCR results for ABCG2 (r = 0.919, P = 0.001; Pearson) but not Bmi-1 (r = −0.311). The results provide evidence of increased density of ABCG2 and Bmi-1-positive populations in malignant and oral potentially malignant lesions and derived cell lines, but that intragroup variability within IHC, flow cytometry, and RT-PCR results compromise the diagnostic potential of these techniques for discriminating oral dysplasia from normal tissue or OSCC

  14. Interleukin-37 expression and its potential role in oral leukoplakia and oral squamous cell carcinoma.

    Science.gov (United States)

    Lin, Lin; Wang, Jiayi; Liu, Dongjuan; Liu, Sai; Xu, Hao; Ji, Ning; Zhou, Min; Zeng, Xin; Zhang, Dunfang; Li, Jing; Chen, Qianming

    2016-05-26

    Interleukin 37 (IL-37) has been reported to play a significant role in innate immune response and to be involved in several kinds of cancers. However, the investigation of association between IL-37 and oral mucosa carcinogenesis hasn't been clearly established. The aim of the study was to assess IL-37 expression and explore its role in oral mucosa carcinogenesis. The expression of IL-37 increased from normal control (NC) to Oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC). Moreover, statistically highly significant difference was present between scores of OLK with and without mild/moderate dysplasia (P oral mucosa carcinogenesis. Overall, IL-37 can be used as a biomarker for early oral tumorigenesis and for malignant transformation risk assessment of premalignant lesions.

  15. Potential for treating tuberculosis with nano drug delivery system

    CSIR Research Space (South Africa)

    Swai, H

    2006-11-01

    Full Text Available www.csir.co.za • Performed in guinea pigs • Similar pathophysiology to humans • Drugs administered orally • Analyzed in lung, spleen and liver • ATD loaded PLGA detectable up to 11 days • Free ATD cleared in 1-2 days • No toxic side effects...

  16. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers.

    Science.gov (United States)

    Lin, Chih-Hung; Chen, Chun-Han; Lin, Zih-Chan; Fang, Jia-You

    2017-04-01

    Chemical and enzymatic barriers in the gastrointestinal (GI) tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs) are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs. Copyright © 2017. Published by Elsevier B.V.

  17. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers

    Directory of Open Access Journals (Sweden)

    Chih-Hung Lin

    2017-04-01

    Full Text Available Chemical and enzymatic barriers in the gastrointestinal (GI tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs.

  18. pH-responsive and enzymatically-responsive hydrogel microparticles for the oral delivery of therapeutic proteins: Effects of protein size, crosslinking density, and hydrogel degradation on protein delivery.

    Science.gov (United States)

    Koetting, Michael Clinton; Guido, Joseph Frank; Gupta, Malvika; Zhang, Annie; Peppas, Nicholas A

    2016-01-10

    Two potential platform technologies for the oral delivery of protein therapeutics were synthesized and tested. pH-responsive poly(itaconic acid-co-N-vinyl-2-pyrrolidone) (P(IA-co-NVP)) hydrogel microparticles were tested in vitro with model proteins salmon calcitonin, urokinase, and rituximab to determine the effects of particle size, protein size, and crosslinking density on oral delivery capability. Particle size showed no significant effect on overall delivery potential but did improve percent release of encapsulated protein over the micro-scale particle size range studied. Protein size was shown to have a significant impact on the delivery capability of the P(IA-co-NVP) hydrogel. We show that when using P(IA-co-NVP) hydrogel microparticles with 3 mol% tetra(ethylene glycol) dimethacrylate crosslinker, a small polypeptide (salmon calcitonin) loads and releases up to 45 μg/mg hydrogel while the mid-sized protein urokinase and large monoclonal antibody rituximab load and release only 19 and 24 μg/mg hydrogel, respectively. We further demonstrate that crosslinking density offers a simple method for tuning hydrogel properties to variously sized proteins. Using 5 mol% TEGDMA crosslinker offers optimal performance for the small peptide, salmon calcitonin, whereas lower crosslinking density of 1 mol% offers optimal performance for the much larger protein rituximab. Finally, an enzymatically-degradable hydrogels of P(MAA-co-NVP) crosslinked with the peptide sequence MMRRRKK were synthesized and tested in simulated gastric and intestinal conditions. These hydrogels offer ideal loading and release behavior, showing no degradative release of encapsulated salmon calcitonin in gastric conditions while yielding rapid and complete release of encapsulated protein within 1h in intestinal conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. The potential for preventing the delivery and perinatal mortality of ...

    African Journals Online (AJOL)

    Objective. To determine the potentiaJ for preventing the delivery and perinatal mortality of low-birth-weight (LBW) babies in a black urban population. Design. Cross-sectionaJ descriptive study. Setting. All women delivering babies weighing less than 2 500 g at Kalafong Hospital in a 6-month period (December 1991 - May ...

  20. Investigating Engineered Ribonucleoprotein Particles to Improve Oral RNAi Delivery in Crop Insect Pests

    Directory of Open Access Journals (Sweden)

    François-Xavier Gillet

    2017-04-01

    Full Text Available Genetically modified (GM crops producing double-stranded RNAs (dsRNAs are being investigated largely as an RNA interference (RNAi-based resistance strategy against crop insect pests. However, limitations of this strategy include the sensitivity of dsRNA to insect gut nucleases and its poor insect cell membrane penetration. Working with the insect pest cotton boll weevil (Anthonomus grandis, we showed that the chimeric protein PTD-DRBD (peptide transduction domain—dsRNA binding domain combined with dsRNA forms a ribonucleoprotein particle (RNP that improves the effectiveness of the RNAi mechanism in the insect. The RNP slows down nuclease activity, probably by masking the dsRNA. Furthermore, PTD-mediated internalization in insect gut cells is achieved within minutes after plasma membrane contact, limiting the exposure time of the RNPs to gut nucleases. Therefore, the RNP provides an approximately 2-fold increase in the efficiency of insect gene silencing upon oral delivery when compared to naked dsRNA. Taken together, these data demonstrate the role of engineered RNPs in improving dsRNA stability and cellular entry, representing a path toward the design of enhanced RNAi strategies in GM plants against crop insect pests.

  1. Investigating Engineered Ribonucleoprotein Particles to Improve Oral RNAi Delivery in Crop Insect Pests.

    Science.gov (United States)

    Gillet, François-Xavier; Garcia, Rayssa A; Macedo, Leonardo L P; Albuquerque, Erika V S; Silva, Maria C M; Grossi-de-Sa, Maria F

    2017-01-01

    Genetically modified (GM) crops producing double-stranded RNAs (dsRNAs) are being investigated largely as an RNA interference (RNAi)-based resistance strategy against crop insect pests. However, limitations of this strategy include the sensitivity of dsRNA to insect gut nucleases and its poor insect cell membrane penetration. Working with the insect pest cotton boll weevil ( Anthonomus grandis ), we showed that the chimeric protein PTD-DRBD (peptide transduction domain-dsRNA binding domain) combined with dsRNA forms a ribonucleoprotein particle (RNP) that improves the effectiveness of the RNAi mechanism in the insect. The RNP slows down nuclease activity, probably by masking the dsRNA. Furthermore, PTD-mediated internalization in insect gut cells is achieved within minutes after plasma membrane contact, limiting the exposure time of the RNPs to gut nucleases. Therefore, the RNP provides an approximately 2-fold increase in the efficiency of insect gene silencing upon oral delivery when compared to naked dsRNA. Taken together, these data demonstrate the role of engineered RNPs in improving dsRNA stability and cellular entry, representing a path toward the design of enhanced RNAi strategies in GM plants against crop insect pests.

  2. Transepithelial transport of PEGylated anionic poly(amidoamine) dendrimers: implications for oral drug delivery.

    Science.gov (United States)

    Sweet, Deborah M; Kolhatkar, Rohit B; Ray, Abhijit; Swaan, Peter; Ghandehari, Hamidreza

    2009-08-19

    The purpose of this work was to assess the impact of PEGylation on transepithelial transport of anionic poly(amidoamine) dendrimers. Cytotoxicity, uptake and transport across Caco-2 cells of PEGylated G3.5 and G4.5 PAMAM dendrimers were studied. Methoxy polyethylene glycol (750 Da) was conjugated to carboxylic acid-terminated PAMAM dendrimers at feed ratios of 1, 2 and 4 PEG per dendrimer. Compared to the control, PEGylation of anionic dendrimers did not significantly alter cytotoxicity up to a concentration of 0.1 mM. PEGylation of G3.5 dendrimers significantly decreased cellular uptake and transepithelial transport while PEGylation of G4.5 dendrimers led to a significant increase in uptake, but also a significant decrease in transport. Dendrimer PEGylation reduced the opening of tight junctions as evidenced by confocal microscopy techniques. Modulation of the tight junctional complex correlated well with changes in PEGylated dendrimer transport and suggests that anionic dendrimers are transported primarily through the paracellular route. PEGylated dendrimers show promise in oral delivery applications where increased functionality for drug conjugation and release is desired.

  3. Formulation and evaluation of gastroretentive microballoons containing baclofen for a floating oral controlled drug delivery system.

    Science.gov (United States)

    Dube, T S; Ranpise, N S; Ranade, A N

    2014-01-01

    The objective of the present study was to fabricate and evaluate a multiparticulate oral gastroretentive dosage form of baclofen characterized by a central large cavity (hollow core) promoting unmitigated floatation with practical applications to alleviate the signs and symptoms of spasticity and muscular rigidity. Solvent diffusion and evaporation procedure were applied to prepare floating microspheres with a central large cavity using various combinations of ethylcellulose (release retardant) and HPMC K4M (release modifier) dissolved in a mixture of dichloromethane and methanol (2:1). The obtained microspheres (700-1000 µm) exhibit excellent floating ability (86 ± 2.00%) and release characteristics with entrapment efficiency of 95.2 ± 0.32%. Microspheres fabricated with ethylcellulose to HPMC K4M in the ratio 8.5:1.5 released 98.67% of the entrapped drug in 12 h. Muscle relaxation caused by baclofen microspheres impairs the rotarod performance for more than 12 h. Abdominal X-ray images showed that the gastroretention period of the floating barium sulfate- labeled microspheres was no less than 10 h. The buoyant baclofen microspheres provide a promising gastroretentive drug delivery system to deliver baclofen in spastic patients with a sustained release rate.

  4. Novel pH responsive polymethacrylic acid-chitosan-polyethylene glycol nanoparticles for oral peptide delivery.

    Science.gov (United States)

    Sajeesh, S; Sharma, Chandra P

    2006-02-01

    In present study, novel pH sensitive polymethacrylic acid-chitosan-polyethylene glycol (PCP) nanoparticles were prepared under mild aqueous conditions via polyelectrolyte complexation. Free radical polymerization of methacrylic acid (MAA) was carried out in presence of chitosan (CS) and polyethylene glycol (PEG) using a water-soluble initiator and particles were obtained spontaneously during polymerization without using organic solvents or surfactants/steric stabilizers. Dried particles were analyzed by scanning electron microscopy (SEM) and particles dispersed in phosphate buffer (pH 7.0) were visualized under transmission electron microscope (TEM). SEM studies indicated that PCP particles have an aggregated and irregular morphology, however, TEM revealed that these aggregated particles were composed of smaller fragments with size less than 1 micron. Insulin and bovine serum albumin (BSA) as model proteins were incorporated into the nanoparticles by diffusion filling method and their in vitro release characteristics were evaluated at pH 1.2 and 7.4. PCP nanoparticles exhibited good protein encapsulation efficiency and pH responsive release profile was observed under in vitro conditions. Trypsin inhibitory effect of these PCP nanoparticles was studied using casein substrate and these particles displayed lesser inhibitory effect than reference polymer carbopol. Preliminary investigation suggests that these particles can serve as good candidate for oral peptide delivery. Copyright 2005 Wiley Periodicals, Inc.

  5. Surface-functionalized polymethacrylic acid based hydrogel microparticles for oral drug delivery.

    Science.gov (United States)

    Sajeesh, S; Bouchemal, K; Sharma, C P; Vauthier, C

    2010-02-01

    Aim of the present work was to develop novel thiol-functionalized hydrogel microparticles based on poly(methacrylic acid)-chitosan-poly(ethylene glycol) (PCP) for oral drug delivery applications. PCP microparticles were prepared by a modified ionic gelation process in aqueous medium. Thiol modification of surface carboxylic acid groups of PCP micro particles was carried out by coupling l-cysteine with a water-soluble carbodiimide. Ellman's method was adopted to quantify the sulfhydryl groups, and dynamic light-scattering technique was used to measure the average particle size. Cytotoxicity of the modified particles was evaluated on Caco 2 cells by MTT assay. Effect of thiol modification on permeability of paracellular marker fluorescence dextran (FD4) was evaluated on Caco 2 cell monolayers and freshly excised rat intestinal tissue with an Ussing chamber set-up. Mucoadhesion experiments were carried out by an ex vivo bioadhesion method with excised rat intestinal tissue. The average size of the PCP microparticles was increased after thiol modification. Thiolated microparticles significantly improved the paracellular permeability of FD4 across Caco 2 cell monolayers, with no sign of toxicity. However, the efficacy of thiolated system remained low when permeation experiments were carried out across excised intestinal membrane. This was attributed to the high adhesion of the thiolated particles on the gut mucosa. Nevertheless, it can be concluded that surface thiolation is an interesting strategy to improve paracellular permeability of hydrophilic macromolecules. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  6. Plant-based vaccines for oral delivery of type 1 diabetes-related autoantigens: Evaluating oral tolerance mechanisms and disease prevention in NOD mice.

    Science.gov (United States)

    Posgai, Amanda L; Wasserfall, Clive H; Kwon, Kwang-Chul; Daniell, Henry; Schatz, Desmond A; Atkinson, Mark A

    2017-02-13

    Autoantigen-specific immunological tolerance represents a central objective for prevention of type 1 diabetes (T1D). Previous studies demonstrated mucosal antigen administration results in expansion of Foxp3 + and LAP + regulatory T cells (Tregs), suggesting oral delivery of self-antigens might represent an effective means for modulating autoimmune disease. Early preclinical experiments using the non-obese diabetic (NOD) mouse model reported mucosal administration of T1D-related autoantigens [proinsulin or glutamic acid decarboxylase 65 (GAD)] delayed T1D onset, but published data are conflicting regarding dose, treatment duration, requirement for combinatorial agents, and extent of efficacy. Recently, dogma was challenged in a report demonstrating oral insulin does not prevent T1D in NOD mice, possibly due to antigen digestion prior to mucosal immune exposure. We used transplastomic plants expressing proinsulin and GAD to protect the autoantigens from degradation in an oral vaccine and tested the optimal combination, dose, and treatment duration for the prevention of T1D in NOD mice. Our data suggest oral autoantigen therapy alone does not effectively influence disease incidence or result in antigen-specific tolerance assessed by IL-10 measurement and Treg frequency. A more aggressive approach involving tolerogenic cytokine administration and/or lymphocyte depletion prior to oral antigen-specific immunotherapy will likely be required to impart durable therapeutic efficacy.

  7. Salivary mRNA markers having the potential to detect oral squamous cell carcinoma segregated from oral leukoplakia with dysplasia.

    Science.gov (United States)

    Michailidou, Evangelia; Tzimagiorgis, Georgios; Chatzopoulou, Fani; Vahtsevanos, Konstantinos; Antoniadis, Konstantinos; Kouidou, Sofia; Markopoulos, Anastasios; Antoniades, Dimitrios

    2016-08-01

    In the current study the presence of extracellular IL-1B, IL-8, OAZ and SAT mRNAs in the saliva was evaluated as a tool in the early detection of oral squamous cell carcinoma. 34 patients with primary oral squamous cell carcinoma stage T1N0M0/T2N0M0, 20 patients with oral leukoplakia and dysplasia (15 patients with mild dysplasia and 5 with severe dysplasia/in situ carcinoma) and 31 matched healthy-control subjects were included in the study. The presence of IL-1B, IL-8, OAZ and SAT mRNA was evaluated in extracellular RNA isolated from saliva samples using sequence-specific primers and real-time RT-PCR. ROC curve analysis was used to estimate the ability of the biomarkers to detect oral squamous cell carcinoma patients. The data reveal that the combination of these four biomarkers provides a good predictive probability of up to 80% (AUC=0.799, p=0.002) for patients with oral squamous cell carcinoma but not patients suffering from oral leukoplakia with dysplasia. Moreover, the combination of only the two biomarkers (SAT and IL-8) also raises a high predictive ability of 75.5% (AUC=0.755, p=0.007) approximately equal to the four biomarkers suggesting the use of the two biomarkers only in the prediction model for oral squamous cell carcinoma patients limiting the economic and health cost in half. SAT and IL-8 mRNAs are present in the saliva in high quality and quantity, with a good discriminatory ability for oral squamous cell carcinoma patients only but not for patients with oral leukoplakia and dysplasia an oral potentially malignant disorder. Copyright © 2016. Published by Elsevier Ltd.

  8. Modified biomolecule as potential vehicle for buccal delivery of doxepin.

    Science.gov (United States)

    Laffleur, Flavia; Zilio, Martina; Shuwisitkul, Duangratana

    2016-10-01

    Doxepin is a traditional tricyclic antidepressant with analgesic and anesthetic properties when applied topically to the mucosa. Doxepin is one approach in treating insomnia and depression in Parkinson's disease. Patients with Parkinson's disease suffer difficulties in swallowing. Therefore, it was the aim of this study to develop a buccal-adhesive delivery system. Pectin was modified with cysteine. Stability assays in form of disintegration assay according to the Ph.Eur were performed. Furthermore, bioadhesiveness on buccal mucosa was investigated incorporating the drug doxepin. The adhesiveness was improved 1.4-fold and revealed a sustained release over 3 h. Taking these findings into account, the modifications render this designed excipient fruitful for buccal delivery.

  9. Transdermal Delivery of Drugs with Microneedles—Potential and Challenges

    Directory of Open Access Journals (Sweden)

    Kevin Ita

    2015-06-01

    Full Text Available Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use.

  10. Microencapsulation as a novel delivery method for the potential antidiabetic drug, Probucol

    Directory of Open Access Journals (Sweden)

    Mooranian A

    2014-09-01

    Full Text Available Armin Mooranian,1 Rebecca Negrulj,1 Nigel Chen-Tan,2 Hesham S Al-Sallami,3 Zhongxiang Fang,4 TK Mukkur,5 Momir Mikov,6,7 Svetlana Golocorbin-Kon,6,7 Marc Fakhoury,8 Gerald F Watts,9 Vance Matthews,10 Frank Arfuso,5 Hani Al-Salami1 1Biotechnology and Drug Development Research Laboratory School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, Western Australia, Australia; 2Faculty of Science and Engineering, Curtin University, Perth, Western Australia, Australia; 3School of Pharmacy, University of Otago, Dunedin, New Zealand; 4School of Public Health, Curtin University, Perth, Western Australia, Australia; 5Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Biomedical Science, Curtin University, Perth, Western Australia, Australia; 6Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Serbia; 7Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Serbia; 8Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada; 9School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia; 10Laboratory for Metabolic Dysfunction, UWA Centre for Medical Research, Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia Introduction: In previous studies, we successfully designed complex multicompartmental microcapsules as a platform for the oral targeted delivery of lipophilic drugs in type 2 diabetes (T2D. Probucol (PB is an antihyperlipidemic and antioxidant drug with the potential to show benefits in T2D. We aimed to create a novel microencapsulated formulation of PB and to examine the shape, size, and chemical, thermal, and rheological properties of these microcapsules in vitro. Method: Microencapsulation was carried out using the Büchi-based microencapsulating system developed in our laboratory. Using the polymer, sodium

  11. Transdermal drug delivery

    Science.gov (United States)

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

  12. Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

    NARCIS (Netherlands)

    van Leeuwen, R. W. F.; Brundel, D. H. S.; Neef, C.; van Gelder, T.; Mathijssen, R. H. J.; Burger, D. M.; Jansman, F. G. A.

    2013-01-01

    Background: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment. Methods: A

  13. Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

    NARCIS (Netherlands)

    R.W.F. van Leeuwen (Roelof); D.H.S. Brundel (D. H S); C. Neef (Cees); T. van Gelder (Teun); A.H.J. Mathijssen (Ron); D.M. Burger (David); F.G.A. Jansman (Frank)

    2013-01-01

    textabstractBackground: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment.

  14. Liposomes coated with thiolated chitosan enhance oral peptide delivery to rats☆

    Science.gov (United States)

    Gradauer, K.; Barthelmes, J.; Vonach, C.; Almer, G.; Mangge, H.; Teubl, B.; Roblegg, E.; Dünnhaupt, S.; Fröhlich, E.; Bernkop-Schnürch, A.; Prassl, R.

    2013-01-01

    The aim of the present study was the in vivo evaluation of thiomer-coated liposomes for an oral application of peptides. For this purpose, salmon calcitonin was chosen as a model drug and encapsulated within liposomes. Subsequently, the drug loaded liposomes were coated with either chitosan–thioglycolic acid (CS–TGA) or an S-protected version of the same polymer (CS–TGA–MNA), leading to an increase in the particle size of about 500 nm and an increase in the zeta potential from approximately − 40 mV to a maximum value of about + 44 mV, depending on the polymer. Coated liposomes were demonstrated to effectively penetrate the intestinal mucus layer where they came in close contact with the underlying epithelium. To investigate the permeation enhancing properties of the coated liposomes ex vivo, we monitored the transport of fluoresceinisothiocyanate-labeled salmon calcitonin (FITC-sCT) through rat small intestine. Liposomes coated with CS–TGA–MNA showed the highest effect, leading to a 3.8-fold increase in the uptake of FITC-sCT versus the buffer control. In vivo evaluation of the different formulations was carried out by the oral application of 40 μg of sCT per rat, either encapsulated within uncoated liposomes, CS–TGA-coated liposomes or CS–TGA–MNA-coated liposomes, or given as a solution serving as negative control. The blood calcium level was monitored over a time period of 24 h. The highest reduction in the blood calcium level, to a minimum of 65% of the initial value after 6 h, was achieved for CS–TGA–MNA-coated liposomes. Comparing the areas above curves (AAC) of the blood calcium levels, CS–TGA–MNA-coated liposomes led to an 8.2-fold increase compared to the free sCT solution if applied orally in the same concentration. According to these results, liposomes coated with S-protected thiomers have demonstrated to be highly valuable carriers for enhancing the oral bioavailability of salmon calcitonin. PMID:24140721

  15. Liposomes coated with thiolated chitosan enhance oral peptide delivery to rats.

    Science.gov (United States)

    Gradauer, K; Barthelmes, J; Vonach, C; Almer, G; Mangge, H; Teubl, B; Roblegg, E; Dünnhaupt, S; Fröhlich, E; Bernkop-Schnürch, A; Prassl, R

    2013-12-28

    The aim of the present study was the in vivo evaluation of thiomer-coated liposomes for an oral application of peptides. For this purpose, salmon calcitonin was chosen as a model drug and encapsulated within liposomes. Subsequently, the drug loaded liposomes were coated with either chitosan-thioglycolic acid (CS-TGA) or an S-protected version of the same polymer (CS-TGA-MNA), leading to an increase in the particle size of about 500 nm and an increase in the zeta potential from approximately -40 mV to a maximum value of about +44 mV, depending on the polymer. Coated liposomes were demonstrated to effectively penetrate the intestinal mucus layer where they came in close contact with the underlying epithelium. To investigate the permeation enhancing properties of the coated liposomes ex vivo, we monitored the transport of fluoresceinisothiocyanate-labeled salmon calcitonin (FITC-sCT) through rat small intestine. Liposomes coated with CS-TGA-MNA showed the highest effect, leading to a 3.8-fold increase in the uptake of FITC-sCT versus the buffer control. In vivo evaluation of the different formulations was carried out by the oral application of 40 μg of sCT per rat, either encapsulated within uncoated liposomes, CS-TGA-coated liposomes or CS-TGA-MNA-coated liposomes, or given as a solution serving as negative control. The blood calcium level was monitored over a time period of 24h. The highest reduction in the blood calcium level, to a minimum of 65% of the initial value after 6h, was achieved for CS-TGA-MNA-coated liposomes. Comparing the areas above curves (AAC) of the blood calcium levels, CS-TGA-MNA-coated liposomes led to an 8.2-fold increase compared to the free sCT solution if applied orally in the same concentration. According to these results, liposomes coated with S-protected thiomers have demonstrated to be highly valuable carriers for enhancing the oral bioavailability of salmon calcitonin. © 2013. Published by Elsevier B.V. All rights reserved.

  16. Development and in vivo evaluation of an oral delivery system for low molecular weight heparin based on thiolated polycarbophil.

    Science.gov (United States)

    Kast, Constantia E; Guggi, Davide; Langoth, Nina; Bernkop-Schnürch, Andreas

    2003-06-01

    It was the purpose of this study to develop a new oral drug delivery system for low molecular weight heparin (LMWH) providing an improved bioavailability and a prolonged therapeutic effect. The permeation enhancing polycarbophil-cysteine conjugate (PCP-Cys) used in this study displayed 111.4 +/- 6.4 microM thiol groups per gram polymer. Permeation studies on freshly excised intestinal mucosa were performed in Ussing chambers demonstrating a 2-fold improved uptake of heparin as a result of the addition of 0.5% (w/v) PCP-Cys and the permeation mediator glutathione (GSH). Tablets containing PCP-Cys, GSH, and 279 IU of LMWH showed a sustained drug release over 4 h. To guarantee the swelling of the polymeric carrier matrix in the small intestine tablets were enteric coated. They were orally given to rats. For tablets being based on the thiomer/GSH system an absolute bioavailability of 19.9 +/- 9.3% (means +/- SD; n = 5) vs. intravenous injection could be achieved. whereas tablets comprising unmodified PCP did not lead to a significant (p < 0.01) heparin concentration in plasma. The permeation enhancing effect and subsequently a therapeutic heparin level was maintained for 24 h after a single dose. Because of the strong and prolonged lasting permeation enhancing effect of the thiomer/GSH system, the oral bioavailability of LMWH could be significantly improved. This new delivery system represents therefore a promising tool for the oral administration of heparin.

  17. Oral delivery of ACE2/Ang-(1-7) bioencapsulated in plant cells protects against experimental uveitis and autoimmune uveoretinitis.

    Science.gov (United States)

    Shil, Pollob K; Kwon, Kwang-Chul; Zhu, Ping; Verma, Amrisha; Daniell, Henry; Li, Qiuhong

    2014-12-01

    Hyperactivity of the renin-angiotensin system (RAS) resulting in elevated Angiotensin II (Ang II) contributes to all stages of inflammatory responses including ocular inflammation. The discovery of angiotensin-converting enzyme 2 (ACE2) has established a protective axis of RAS involving ACE2/Ang-(1-7)/Mas that counteracts the proinflammatory and hypertrophic effects of the deleterious ACE/AngII/AT1R axis. Here we investigated the hypothesis that enhancing the systemic and local activity of the protective axis of the RAS by oral delivery of ACE2 and Ang-(1-7) bioencapsulated in plant cells would confer protection against ocular inflammation. Both ACE2 and Ang-(1-7), fused with the non-toxic cholera toxin subunit B (CTB) were expressed in plant chloroplasts. Increased levels of ACE2 and Ang-(1-7) were observed in circulation and retina after oral administration of CTB-ACE2 and Ang-(1-7) expressing plant cells. Oral feeding of mice with bioencapsulated ACE2/Ang-(1-7) significantly reduced endotoxin-induced uveitis (EIU) in mice. Treatment with bioencapsulated ACE2/Ang-(1-7) also dramatically decreased cellular infiltration, retinal vasculitis, damage and folding in experimental autoimmune uveoretinitis (EAU). Thus, enhancing the protective axis of RAS by oral delivery of ACE2/Ang-(1-7) bioencapsulated in plant cells provide an innovative, highly efficient and cost-effective therapeutic strategy for ocular inflammatory diseases.

  18. A novel oral delivery system consisting in "drug-in cyclodextrin-in nanostructured lipid carriers" for poorly water-soluble drug: vinpocetine.

    Science.gov (United States)

    Lin, Congcong; Chen, Fen; Ye, Tiantian; Zhang, Lina; Zhang, Wenji; Liu, Dandan; Xiong, Wei; Yang, Xinggang; Pan, Weisan

    2014-04-25

    The purpose of this study was to develop a new delivery system based on drug cyclodextrin (CD) complexation and loading into nanostructured lipid carriers (NLC) to improve the oral bioavailability of vinpocetine (VP). Three different CDs and three different methods to obtain solid vinpocetine-cyclodextrin-tartaric acid complexes (VP-CD-TA) were contrasted. The co-evaporation vinpocetine-β-cyclodextrin-tartaric acid loaded NLC (VP-β-CD-TA COE-loaded NLC) was obtained by emulsification ultrasonic dispersion method. VP-β-CD-TA COE-loaded NLC was suitably characterized for particle size, polydispersity index, zeta potential, entrapment efficiency and the morphology. The crystallization of drug in VP-CD-TA and NLC was investigated by differential scanning calorimetry (DSC). The in vitro release study was carried out at pH 1.2, pH 6.8 and pH 7.4 medium. New Zealand rabbits were applied to investigate the pharmacokinetic behavior in vivo. The VP-β-CD-TA COE-loaded NLC presented a superior physicochemical property and selected to further study. In the in vitro release study, VP-β-CD-TA COE-loaded NLC exhibited a higher dissolution rate in the pH 6.8 and pH 7.4 medium than VP suspension and VP-NLC. The relative bioavailability of VP-β-CD-TA COE-loaded NLC was 592% compared with VP suspension and 92% higher than VP-NLC. In conclusion, the new formulation significantly improved bioavailability of VP for oral delivery, demonstrated a perspective way for oral delivery of poorly water-soluble drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Preparation and Evaluation of Enteric-Coated Chitosan Derivative-Based Microparticles Loaded with Salmon Calcitonin as an Oral Delivery System

    Directory of Open Access Journals (Sweden)

    Hiraku Onishi

    2016-09-01

    Full Text Available Background: The production of protein drugs has recently increased due to advances in biotechnology, but their clinical use is generally limited to parenteral administration due to low absorption in non-parenteral administration. Therefore, non-parenteral delivery systems allowing sufficient absorption draw much attention. Methods: Microparticles (MP were prepared using chitosan-4-thio-butylamidine conjugate (Ch-TBA, trimethyl-chitosan (TMC, and chitosan (Ch. Using salmon calcitonin (sCT as a model protein drug, Ch-TBA-, Ch-TBA/TMC (4/1-, and Ch-based MP were produced, and their Eudragit L100 (Eud-coated MP, named Ch-TBA-MP/Eud, Ch-TBA/TMC-MP/Eud, and Ch-MP/Eud, respectively, were prepared as oral delivery systems. These enteric-coated microparticles were examined in vitro and in vivo. Results: All microparticles before and after enteric coating had a submicron size (600–800 nm and micrometer size (1300–1500 nm, respectively. In vitro release patterns were similar among all microparticles; release occurred gradually, and the release rate was slower at pH 1.2 than at pH 6.8. In oral ingestion, Ch-TBA-MP/Eud suppressed plasma Ca levels most effectively among the microparticles tested. The relative effectiveness of Ch-TBA-MP/Eud to the intramuscular injection was 8.6%, while the sCT solution showed no effectiveness. Conclusion: The results suggest that Eud-coated Ch-TBA-based microparticles should have potential as an oral delivery system of protein drugs.

  20. Chloroplast-derived vaccine antigens and biopharmaceuticals: protocols for expression, purification, or oral delivery and functional evaluation.

    Science.gov (United States)

    Singh, N Dolendro; Ding, Yi; Daniell, Henry

    2009-01-01

    Many vaccine antigens and biopharmaceutical proteins have been expressed at high levels via the chloroplast genome and their functionality has been evaluated using in vitro assays in cell cultures (i.e., macrophage lysis assay, inhibition of vesicular stomatitis virus-induced cytopathicity in baby hamster kidney cells, or inhibition of human HIV infection in TZM-BL cells) as well as protection after challenge with bacterial or viral pathogens or antitumor assays or delay the onset of insulitis in suitable animal models. Production of therapeutic proteins in chloroplasts eliminates the expensive fermentation technology. Moreover, oral delivery of chloroplast-derived therapeutic proteins eliminates expensive purification steps, cold storage, cold transportation, and delivery via sterile needles, thereby further decreasing their cost. In this chapter, we describe detailed protocols for chloroplast transformation including the construction of chloroplast transformation vectors, delivery of DNA into plant cells using particle bombardment, selection and regeneration of transformants by tissue culture, confirmation of transgene integration into the chloroplast genome and homoplasmy, evaluation of foreign gene expression, purification of foreign protein, or oral delivery via bioencapsulation, functional evaluation using in vitro and in vivo assays, and evaluation of immunity after challenge with pathogens in suitable animal models.

  1. Antibiotic treatment at delivery shapes the initial oral microbiome in neonates

    OpenAIRE

    Gomez-Arango, Luisa F.; Barrett, Helen L.; McIntyre, H. David.; Callaway, Leonie K.; Morrison, Mark; Dekker Nitert, Marloes

    2017-01-01

    Oral microorganisms are important determinants of health and disease. The source of the initial neonatal microbiome and the factors dictating initial human oral microbiota development are unknown. This study aimed to investigate this in placental, oral and gut microbiome profiles from 36 overweight or obese mother-baby dyads as determined by 16S rRNA sequencing. Expression of five antibiotic resistance genes of the ?-lactamase class was analysed in the infant oral microbiota samples by QPCR. ...

  2. Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery

    Science.gov (United States)

    Hou, Lin; Shi, Yuyang; Jiang, Guixiang; Liu, Wei; Han, Huili; Feng, Qianhua; Ren, Junxiao; Yuan, Yujie; Wang, Yongchao; Shi, Jinjin; Zhang, Zhenzhong

    2016-08-01

    A safe and efficient nanocomposite hydrogel for colon cancer drug delivery was synthesized using pH-sensitive and biocompatible graphene oxide (GO) containing azoaromatic crosslinks as well as poly (vinyl alcohol) (PVA) (GO-N=N-GO/PVA composite hydrogels). Curcumin (CUR), an anti-cancer drug, was encapsulated successfully into the hydrogel through a freezing and thawing process. Fourier transform infrared spectroscopy, scanning electron microscopy and Raman spectroscopy were performed to confirm the formation and morphological properties of the nanocomposite hydrogel. The hydrogels exhibited good swelling properties in a pH-sensitive manner. Drug release studies under conditions mimicking stomach to colon transit have shown that the drug was protected from being released completely into the physiological environment of the stomach and small intestine. In vivo imaging analysis, pharmacokinetics and a distribution of the gastrointestinal tract experiment were systematically studied and evaluated as colon-specific drug delivery systems. All the results demonstrated that GO-N=N-GO/PVA composite hydrogels could protect CUR well while passing through the stomach and small intestine to the proximal colon, and enhance the colon-targeting ability and residence time in the colon site. Therefore, CUR loaded GO-N=N-GO/PVA composite hydrogels might potentially provide a theoretical basis for the treatment of colon cancer with high efficiency and low toxicity.

  3. [Potentially malignant character of oral lichen planus and lichenoid lesions].

    Science.gov (United States)

    Mares, S; Ben Slama, L; Gruffaz, F; Goudot, P; Bertolus, C

    2013-11-01

    Many authors have reported the possible malignant transformation of oral lichen. The incidence of this event remains controversial. Many authors make a distinction between the "true" oral lichen planus (OLP) and lichenoid lesions (LL) according to the WHO clinical and histological classification. For these authors an increased risk of development of oral cancer could occur only on LL. Our aim was to check this hypothesis on a cohort followed for 10 years. We included patients who were referred to our team for the first time between 1995 and 1997, still followed in 2010, with a histological diagnosis of buccal lichen planus. We classified lesions as OLP or LL according to the WHO clinical and histological classification: the two clinical criteria for OLP were a reticulated aspect and bilateral and symmetric lesions. Three histological criteria were necessary for the diagnosis: dense inflammatory infiltrate in the upper lamina propria, liquefaction degeneration of basal keratinocytes, and no signs of dysplasia. The final diagnosis was OLP, when all clinical ad histological criteria were met otherwise it was LL. We studied the patient's outcome between their first consultations and May 2010. Thirty-two patients, whose data was available, met inclusion criteria. Eight were diagnosed with OLP and 24 with LL. The mean follow-up was 164 months [154-183]. No oral cancer was observed in the OLP group. Two patients in the LL group presented with oral cancer after 45 and 143 months of follow-up. Malignant transformations were observed only in the LL group. Our results correlate with those of Van Der Meij et al. published in 2006. The strict use of the WHO diagnostic criteria seems to allow identifying patients at risk of developing oral cancer (LL) and others with only a benign course of this chronic oral mucosal disease. These results need to be confirmed by prospective multicentric studies. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. Income inequality in the United States and its potential effect on oral health.

    Science.gov (United States)

    Moeller, Jamie; Starkel, Rebecca; Quiñonez, Carlos; Vujicic, Marko

    2017-06-01

    The authors explored the relationship between income inequality and self-reported oral health and oral health-related quality of life. The authors used an online survey to gather data about US adults' perceptions of their overall oral health and how oral health affected their quality of life. The authors categorized respondents as coming from areas of low, medium, or high income inequality on the basis of a county-level Gini coefficient. Results of χ 2 tests and an analysis of variance indicated that there was a significant association between income inequality and oral health as measured by using the overall condition of the mouth and teeth, life satisfaction, and frequency of experiencing functional and social problems related to oral health. Generally, adults from areas of lower income inequality reported better oral health and oral health-related quality of life. Income inequality has the potential to affect both functional and social dimensions of oral health, possibly through a psychosocial pathway. Future research is necessary to determine whether any causal link exists. Our findings may inform oral health policy. Long-term policies designed to improve the oral health of Americans could work best when supported by policies designed to reduce levels of income inequality, and thereby, may reduce oral health inequalities. Further research is needed to examine the effectiveness of such policies. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

  5. Microencapsulation of indocyanine green for potential applications in image-guided drug delivery.

    Science.gov (United States)

    Zhu, Zhiqiang; Si, Ting; Xu, Ronald X

    2015-02-07

    We present a novel process to encapsulate indocyanine green (ICG) in liposomal droplets at high concentration for potential applications in image-guided drug delivery. The microencapsulation process follows two consecutive steps of droplet formation by liquid-driven coaxial flow focusing (LDCFF) and solvent removal by oil phase dewetting. These biocompatible lipid vesicles may have important applications in drug delivery and fluorescence imaging.

  6. Scalable fabrication of size-controlled chitosan nanoparticles for oral delivery of insulin.

    Science.gov (United States)

    He, Zhiyu; Santos, Jose Luis; Tian, Houkuan; Huang, Huahua; Hu, Yizong; Liu, Lixin; Leong, Kam W; Chen, Yongming; Mao, Hai-Quan

    2017-06-01

    Controlled delivery of protein would find diverse therapeutic applications. Formulation of protein nanoparticles by polyelectrolyte complexation between the protein and a natural polymer such as chitosan (CS) is a popular approach. However, the current method of batch-mode mixing faces significant challenges in scaling up while maintaining size control, high uniformity, and high encapsulation efficiency. Here we report a new method, termed flash nanocomplexation (FNC), to fabricate insulin nanoparticles by infusing aqueous solutions of CS, tripolyphosphate (TPP), and insulin under rapid mixing condition (Re > 1600) in a multi-inlet vortex mixer. In comparison with the bulk-mixing method, the optimized FNC process produces CS/TPP/insulin nanoparticles with a smaller size (down to 45 nm) and narrower size distribution, higher encapsulation efficiency (up to 90%), and pH-dependent nanoparticle dissolution and insulin release. The CS/TPP/insulin nanoparticles can be lyophilized and reconstituted without loss of activity, and produced at a throughput of 5.1 g h -1 when a flow rate of 50 mL min -1 is used. Evaluated in a Type I diabetes rat model, the smaller nanoparticles (45 nm and 115 nm) control the blood glucose level through oral administration more effectively than the larger particles (240 nm). This efficient, reproducible and continuous FNC technique is amenable to scale-up in order to address the critical barrier of manufacturing for the translation of protein nanoparticles. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Potentially malignant disorders of the oral cavity: a clinical study.

    Science.gov (United States)

    Shukla, Anirudh

    2014-01-01

    Oral cancers in India, unlike in the West are the most common cancers encountered, be it a primary or a tertiary referral practice. This makes the study and management of these cancers an important issue especially for the otolaryngologist. It is well known that the most common variant of oral cancers is the squamous cell carcinoma. Also the etiology is well established; with tobacco use in both smoking and smokeless forms, alcohol, betel nut and recently the Human Papilloma virus infection being implicated. Certain conditions which definitely increase the probability of getting oral cancers are known and this study aims in revisiting these aspects of pre-malignancy. The progression from a pre-cancerous lesion/condition to frank cancer is well established across many studies and many specialties. Also timely recognizing these pre-cancerous conditions and administration of proper treatment will greatly help in reducing the morbidity and mortality from subsequent much advanced and dangerous oral cancer. Keeping these facts in mind this study was planned to study the established pre-cancerous lesions which are known to progress to oral cancers.

  8. Genipin Cross-Linked Polymeric Alginate-Chitosan Microcapsules for Oral Delivery: In-Vitro Analysis

    Directory of Open Access Journals (Sweden)

    Hongmei Chen

    2009-01-01

    Full Text Available We have previously reported the preparation of the genipin cross-linked alginate-chitosan (GCAC microcapsules composed of an alginate core with a genipin cross-linked chitosan membrane. This paper is the further investigation on their structural and physical characteristics. Results showed that the GCAC microcapsules had a smooth and dense surface and a networked interior. Cross-linking by genipin substantially reduced swelling and physical disintegration of microcapsules induced by nongelling ions and calcium sequestrants. Strong resistance to mechanical shear forces and enzymatic degradation was observed. Furthermore, the GCAC membranes were permeable to bovine serum albumin and maintained a molecular weight cutoff at 70 KD, analogous to the widely studied alginate-chitosan, and alginate-poly-L-lysine-alginate microcapsules. The release features and the tolerance of the GCAC microcapsules in the stimulated gastrointestinal environment were also investigated. This GCAC microcapsule formulation offers significant potential as a delivery vehicle for many biomedical applications.

  9. Lipid drug conjugate nanoparticle as a novel lipid nanocarrier for the oral delivery of decitabine: ex vivo gut permeation studies

    International Nuclear Information System (INIS)

    Neupane, Yub Raj; Sabir, M D; Ahmad, Nafees; Ali, Mushir; Kohli, Kanchan

    2013-01-01

    The purpose of this study was to develop lipid drug conjugate (LDC) nanoparticles of decitabine (DCB) using stearic acid as a lipid to increase the permeability of the drug along with its protection from chemical degradation. The LDC was prepared by salt formation of DCB with stearic acid and followed by cold homogenization technique to produce the LDC nanoparticles. The role of key independent variables influencing on dependent variables were determined by using a Box–Behnken design. The optimized batch revealed spherical morphology under TEM analysis with particle size of 202.6 ± 1.65 nm and 0.334 ± 0.987 PDI. The zeta potential and %EE were found to be −33.6 ± 0.845 mV and 68.89% ± 0.59 respectively. Lyophilized powder showed the crystalline structure under DSC analysis. In vitro release studies showed the initial burst release followed by a sustained release up to 24 h in PBS pH 7.4 and the data were further studied using release kinetic models which revealed the first-order model as a best-fitting model. Ex vivo gut permeation studies proved that the formulation containing lipid and surfactants has a higher permeability than the plain drug solution with nearly fourfold increase in the apparent permeability coefficients. Finally, LDC nanoparticles prepared by using stearic acid as a lipid and surfactants as Tween 80, Poloxamer 188, and Labrasol in equal ratio possess high potential for the oral delivery of hydrophilic drugs. (paper)

  10. Lipid drug conjugate nanoparticle as a novel lipid nanocarrier for the oral delivery of decitabine: ex vivo gut permeation studies

    Science.gov (United States)

    Neupane, Yub Raj; Sabir, M. D.; Ahmad, Nafees; Ali, Mushir; Kohli, Kanchan

    2013-10-01

    The purpose of this study was to develop lipid drug conjugate (LDC) nanoparticles of decitabine (DCB) using stearic acid as a lipid to increase the permeability of the drug along with its protection from chemical degradation. The LDC was prepared by salt formation of DCB with stearic acid and followed by cold homogenization technique to produce the LDC nanoparticles. The role of key independent variables influencing on dependent variables were determined by using a Box-Behnken design. The optimized batch revealed spherical morphology under TEM analysis with particle size of 202.6 ± 1.65 nm and 0.334 ± 0.987 PDI. The zeta potential and %EE were found to be -33.6 ± 0.845 mV and 68.89% ± 0.59 respectively. Lyophilized powder showed the crystalline structure under DSC analysis. In vitro release studies showed the initial burst release followed by a sustained release up to 24 h in PBS pH 7.4 and the data were further studied using release kinetic models which revealed the first-order model as a best-fitting model. Ex vivo gut permeation studies proved that the formulation containing lipid and surfactants has a higher permeability than the plain drug solution with nearly fourfold increase in the apparent permeability coefficients. Finally, LDC nanoparticles prepared by using stearic acid as a lipid and surfactants as Tween 80, Poloxamer 188, and Labrasol in equal ratio possess high potential for the oral delivery of hydrophilic drugs.

  11. Optical imaging for the diagnosis of oral cancer and oral potentially malignant disorders

    Science.gov (United States)

    Yoshida, K.

    2016-03-01

    Optical Imaging is being conducted as a therapeutic non-invasive. Many kinds of the light source are selected for this purpose. Recently the oral cancer screening is conducted by using light-induced tissue autofluorescence examination such as several kinds of handheld devices. However, the mechanism of its action is still not clear. Therefore basic experimental research was conducted. One of auto fluorescence Imaging (AFI) device, VELscopeTM and near-infrared (NIR) fluorescence imaging using ICG-labeled antibody as a probe were compared using oral squamous cell carcinoma (OSCC) mouse models. The experiments revealed that intracutaneous tumor was successfully visualized as low density image by VELscopeTM and high density image by NIR image. In addition, VELscopeTM showed higher sensitivity and lower specificity than that of NIR fluorescence imaging and the sensitivity of identification of carcinoma areas with the VELscopeTM was good results. However, further more studies were needed to enhance the screening and diagnostic uses, sensitivity and specificity for detecting malignant lesions and differentiation from premalignant or benign lesions. Therefore, additional studies were conducted using a new developed near infrared (NIR) fluorescence imaging method targeting podoplanine (PDPN) which consists of indocyanine green (ICG)-labeled anti-human podoplanin antibody as a probe and IVIS imaging system or a handy realtime ICG imaging device that is overexpressed in oral malignant neoplasm to improve imaging for detection of early oral malignant neoplasm. Then evaluated for its sensitivity and specificity for detection of oral malignant neoplasm in xenografted mice model and compared with VELscopeTM. The results revealed that ICG fluorescence imaging method and VELscopeTM had the almost the same sensitivity for detection of oral malignant neoplasm. The current topics of optical imaging about oral malignant neoplasm were reviewed.

  12. Tragacanth as an oral peptide and protein delivery carrier: Characterization and mucoadhesion.

    Science.gov (United States)

    Nur, M; Ramchandran, L; Vasiljevic, T

    2016-06-05

    Biopolymers such as tragacanth, an anionic polysaccharide gum, can be alternative polymeric carrier for physiologically important peptides and proteins. Characterization of tragacanth is thus essential for providing a foundation for possible applications. Rheological studies colloidal solution of tragacanth at pH 3, 5 or 7 were carried out by means of steady shear and small amplitude oscillatory measurements. Tragacanth mucoadhesivity was also analyzed using an applicable rheological method and compared to chitosan, alginate and PVP. The particle size and zeta potential were measured by a zetasizer. Thermal properties of solutions were obtained using a differential scanning calorimetry. The solution exhibited shear-thinning characteristics. The value of the storage modulus (G') and the loss modulus (G″) increased with an increase in angular frequency (Ω). In all cases, loss modulus values were higher than storage values (G″>G') and viscous character was, therefore, dominant. Tragacanth and alginate showed a good mucoadhesion. Tragacanth upon dispersion created particles of a submicron size with a negative zeta potential (-7.98 to -11.92 mV). These properties were pH dependant resulting in acid gel formation at pH 3.5. Tragacanth has thus a potential to be used as an excipient for peptide/protein delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Targeted delivery of antigen to intestinal dendritic cells induces oral tolerance and prevents autoimmune diabetes in NOD mice.

    Science.gov (United States)

    Chen, Yulin; Wu, Jie; Wang, Jiajia; Zhang, Wenjing; Xu, Bohui; Xu, Xiaojun; Zong, Li

    2018-03-15

    The intestinal immune system is an ideal target to induce immune tolerance physiologically. However, the efficiency of oral protein antigen delivery is limited by degradation of the antigen in the gastrointestinal tract and poor uptake by antigen-presenting cells. Gut dendritic cells (DCs) are professional antigen-presenting cells that are prone to inducing antigen-specific immune tolerance. In this study, we delivered the antigen heat shock protein 65-6×P277 (H6P) directly to the gut DCs of NOD mice through oral vaccination with H6P-loaded targeting nanoparticles (NPs), and investigated the ability of this antigen to induce immune tolerance to prevent autoimmune diabetes in NOD mice. A targeting NP delivery system was developed to encapsulate H6P, and the ability of this system to protect and facilitate H6P delivery to gut DCs was assessed. NOD mice were immunised with H6P-loaded targeting NPs orally once a week for 7 weeks and the onset of diabetes was assessed by monitoring blood glucose levels. H6P-loaded targeting NPs protected the encapsulated H6P from degradation in the gastrointestinal tract environment and significantly increased the uptake of H6P by DCs in the gut Peyer's patches (4.1 times higher uptake compared with the control H6P solution group). Oral vaccination with H6P-loaded targeting NPs induced antigen-specific T cell tolerance and prevented diabetes in 100% of NOD mice. Immune deviation (T helper [Th]1 to Th2) and CD4 + CD25 + FOXP3 + regulatory T cells were found to participate in the induction of immune tolerance. In this study, we successfully induced antigen-specific T cell tolerance and prevented the onset of diabetes in NOD mice. To our knowledge, this is the first attempt at delivering antigen to gut DCs using targeting NPs to induce T cell tolerance.

  14. Pluronic-Functionalized Silica-Lipid Hybrid Microparticles: Improving the Oral Delivery of Poorly Water-Soluble Weak Bases.

    Science.gov (United States)

    Rao, Shasha; Richter, Katharina; Nguyen, Tri-Hung; Boyd, Ben J; Porter, Christopher J H; Tan, Angel; Prestidge, Clive A

    2015-12-07

    A Pluronic-functionalized silica-lipid hybrid (Plu-SLH) microparticle system for the oral delivery of poorly water-soluble, weak base drugs is reported for the first time. A highly effective Plu-SLH microparticle system was composed of Labrasol as the lipid phase, Pluronic F127 as the polymeric precipitation inhibitor (PPI), and silica nanoparticles as the solid carrier. For the model drug cinnarizine (CIN), the Plu-SLH delivery system was shown to offer significant biopharmaceutical advantages in comparison with unformulated drug and drug in the silica-lipid hybrid (SLH) system. In vitro two-phase dissolution studies illustrated significantly reduced pH provoked CIN precipitation and an 8- to 14-fold improvement in the extent of dissolution in intestinal conditions. In addition, under simulated intestinal digesting conditions, the Plu-SLH provided approximately three times more drug solubilization than the SLH. Oral administration in rats resulted in superior bioavailability for Plu-SLH microparticles, i.e., 1.6- and 2.1-fold greater than the SLH and the unformulated CIN, respectively. A physical mixture of Pluronic and SLH (Plu&SLH), having the same composition as Plu-SLH, was also evaluated, but showed no significant increase in CIN absorption when compared to unmodified CIN or SLH. This work represents the first study where different methods of incorporating PPI to formulate solid-state lipid-based formulations were compared for the impact on the biopharmaceutical performance. The data suggest that the novel physicochemical properties and structure of the fabricated Plu-SLH microparticle delivery system play an important role in facilitating the synergistic advantage of Labrasol and Pluronic F127 in preventing drug precipitation, and the Plu-SLH provides efficient oral delivery of poorly water-soluble weak bases.

  15. Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice.

    Science.gov (United States)

    Verma, Dheeraj; Moghimi, Babak; LoDuca, Paul A; Singh, Harminder D; Hoffman, Brad E; Herzog, Roland W; Daniell, Henry

    2010-04-13

    To address complications of pathogenic antibody or life-threatening anaphylactic reactions in protein replacement therapy for patients with hemophilia or other inherited protein deficiencies, we have developed a prophylactic protocol using a murine hemophilia B model. Oral delivery of coagulation factor IX fused with cholera toxin beta-subunit (with or without a furin cleavage site; CTB-FFIX or CTB-FIX), expressed in chloroplasts (up to 3.8% soluble protein or 0.4 mg/g leaf tissue), bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies (undetectable or up to 100-fold less than controls). Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after four to six exposures to intravenous F.IX. Whereas only 20-25% of control animals survived after six to eight F.IX doses, 90-93% of F.IX-fed mice survived 12 injections without signs of allergy or anaphylaxis. Immunostaining confirmed delivery of F.IX to Peyer's patches in the ileum. Within 2-5 h, feeding of CTB-FFIX additionally resulted in systemic delivery of F.IX antigen. This high-responder strain of hemophilia B mice represents a new animal model to study anaphylactic reactions. The protocol was effective over a range of oral antigen doses (equivalent to 5-80 microg recombinant F.IX/kg), and controlled inhibitor formation and anaphylaxis long-term, up to 7 months (approximately 40% life span of this mouse strain). Oral antigen administration caused a deviant immune response that suppressed formation of IgE and inhibitory antibodies. This cost-effective and efficient approach of antigen delivery to the gut should be applicable to several genetic diseases that are prone to pathogenic antibody responses during treatment.

  16. Radiolabelling of potential colonic delivery systems by neutron activation. An evaluation based on physiochemical properties of excipients and formulations

    International Nuclear Information System (INIS)

    Ahrabi, Sayeh

    1999-01-01

    The effects of neutron irradiation on the physicochemical properties of some potential release-controlling excipients for oral delivery to colon (based on microbially degradable polysaccharide or a combination of pH- and time-dependent mechanisms) were initially investigated. The aim was to choose the most irradiation-resistant ones for the development of a colonic delivery system to be radiolabelled by the neutron activation procedure. However, no correlation between the extent of irradiation-induced changes of the release-controlling polymers and the in vitro properties of the final formulation was observed. Incorporation of samarium oxide (Sm 2 O 3 ) resulted in retardation of the drug release through the diffusion layer. The influence of neutron activation factors on the properties of some suppository combinations was also studied. The effect of the admixture of Sm 2 O 3 on the dissolution and disintegration of the suppositories was more profound than the effect of neutron irradiation. In hydrophilic suppositories, the effect of Sm 2 O 3 was dependent on the type, amount and the physicochemical characteristics of the incorporated drug. In lipophilic suppositories, the release-controlling effect of Sm 2 O 3 was hypothesised to be due to its insoluble micronised particles blocking the drug diffusion layer. The neutron activation procedure could be utilised for radiolabelling potential oral and rectal colonic drug delivery systems. However, to avoid alteration in the crucial in vitro characteristics of the formulations, the amount, the particle size and the aggregated particle characteristics of the lanthanide salt (e.g. Sm 2 O 3 or samarium stearate) together with the neutron irradiation dose should be controlled precisely for each dosage system. For the systems investigated in this work the release-controlling mechanism of the dosage form seems to be a key parameter to predict the extent of the influence of neutron activation factors on the in vitro properties

  17. Houttuynia cordata modulates oral innate immune mediators: potential role of herbal plant on oral health.

    Science.gov (United States)

    Satthakarn, S; Chung, W O; Promsong, A; Nittayananta, W

    2015-05-01

    Epithelial cells play an active role in oral innate immunity by producing various immune mediators. Houttuynia cordata Thunb (H. cordata), a herbal plant found in Asia, possesses many activities. However, its impacts on oral innate immunity have never been reported. The aim of this study was to determine the effects of H. cordata extract on the expression of innate immune mediators produced by oral epithelial cells. Primary gingival epithelial cells (GECs) were treated with various concentrations of the extract for 18 h. The gene expression of hBD2, SLPI, cytokines, and chemokines was measured using quantitative real-time RT-PCR. The secreted proteins in the culture supernatants were detected by ELISA or Luminex assay. Cytotoxicity of the extract was assessed using CellTiter-Blue Assay. H. cordata significantly induced the expression of hBD2, SLPI, IL-8, and CCL20 in a dose-dependent manner without cytotoxicity. The secreted hBD2 and SLPI proteins were modulated, and the levels of IL-2, IL-6, IL-8, and IFN-γ were significantly induced by the extract. Our data indicated that H. cordata can modulate oral innate immune mediators. These findings may lead to the development of new topical agents from H. cordata for the prevention and treatment of immune-mediated oral diseases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Bioavailability Enhancement of Paclitaxel via a Novel Oral Drug Delivery System: Paclitaxel-Loaded Glycyrrhizic Acid Micelles

    Directory of Open Access Journals (Sweden)

    Fu-Heng Yang

    2015-03-01

    Full Text Available Paclitaxel (PTX, taxol, a classical antitumor drug against a wide range of tumors, shows poor oral bioavailability. In order to improve the oral bioavailability of PTX, glycyrrhizic acid (GA was used as the carrier in this study. This was the first report on the preparation, characterization and the pharmacokinetic study in rats of PTX-loaded GA micelles The PTX-loaded micelles, prepared with ultrasonic dispersion method, displayed small particle sizes and spherical shapes. Differential scanning calorimeter (DSC thermograms indicated that PTX was entrapped in the GA micelles and existed as an amorphous state. The encapsulation efficiency was about 90%, and the drug loading rate could reach up to 7.90%. PTX-loaded GA micelles displayed a delayed drug release compared to Taxol in the in vitro release experiment. In pharmacokinetic study via oral administration, the area under the plasma concentration-time curve (AUC0→24 h of PTX-loaded GA micelles was about six times higher than that of Taxol (p < 0.05. The significant oral absorption enhancement of PTX from PTX-loaded GA micelles could be largely due to the increased absorption in jejunum and colon intestine. All these results suggested that GA would be a promising carrier for the oral delivery of PTX.

  19. Evaluation of Potential Effect of Menthol Solution on Oral Hygiene ...

    African Journals Online (AJOL)

    Purpose: To test the effect of menthol extract on the oral hygiene status of dental students of Faculty of Dentistry, Al- Mustansiriya University, Baghdad, Iraq. Methods: A solution (18 mg %) of menthol was prepared by dissolving menthol crystals in absolute ethanol. Chlorhexidine (CHX, 0.2 %) and deionized water were used ...

  20. Healing Potentials of Oral Moringa Oleifera Leaves Extract and ...

    African Journals Online (AJOL)

    Summary: The effects of oral dose of aqueous extract of Moringa oleifera and tetracycline antibiotics on cutaneous wounds infected with Staphylococcus aureus were studied in eighteen adult wistar rats (159±31.5g) randomized into three groups: Group A, n = 6, Moringa oleifera-(300 mg/kg). Group B, n = 6, tetracycline (9.4 ...

  1. Evaluation of Potential Effect of Menthol Solution on Oral Hygiene ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research April 2015; 14 (4): 687-692 ... Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, ... Keywords: Menthol mouth rinse, Chlorhexidine, Dental plaque, Gingivitis, Oral hygiene ... International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index ...

  2. Poor oral health, a potential new geriatric syndrome

    NARCIS (Netherlands)

    Putten, G.J. van der; Baat, C. de; Visschere, L. De; Schols, J.

    2014-01-01

    This article presents a brief introduction to the medical aspects of ageing and age-related diseases, and to some geriatric syndromes, followed by a discussion on their impact on general and oral healthcare provision to community-dwelling older people. Recent investigations suggest that inflammation

  3. Insulin Inclusion into a Tragacanth Hydrogel: An Oral Delivery System for Insulin

    Directory of Open Access Journals (Sweden)

    Mokhamad Nur

    2018-01-01

    Full Text Available Nanoparticles or microparticles created by physical complexation between two polyelectrolytes may have a prospective use as an excipient for oral insulin administration. Natural polymers such as tragacanth, alginate, dextran, pullulan, hyaluronic acid, gelatin and chitosan can be potential candidates for this purpose. In this research, insulin particles were prepared by the inclusion of insulin into a tragacanth hydrogel. The effect of the pH and concentration relationship involving polyelectrolytes offering individual particle size and zeta potential was assessed by zetasizer and scanning electron microscopy (SEM. Insulin–tragacanth interactions at varying pH (3.7, 4.3, 4.6, or 6, and concentration (0.1%, 0.5%, or 1% w/w were evaluated by differential scanning calorimetry (DSC and ATR Fourier transform infrared (ATR-FTIR analysis. Individual and smaller particles, approximately 800 nm, were acquired at pH 4.6 with 0.5% of tragacanth. The acid gelation test indicated that insulin could be entrapped in the physical hydrogel of tragacanth. DSC thermograms of insulin–tragacanth showed shifts on the same unloaded tragacanth peaks and suggested polyelectrolyte–protein interactions at a pH close to 4.3–4.6. FTIR spectra of tragacanth–insulin complexes exhibited amide absorption bands featuring in the protein spectra and revealed the creation of a new chemical substance.

  4. Insulin Inclusion into a Tragacanth Hydrogel: An Oral Delivery System for Insulin

    Science.gov (United States)

    Vasiljevic, Todor

    2018-01-01

    Nanoparticles or microparticles created by physical complexation between two polyelectrolytes may have a prospective use as an excipient for oral insulin administration. Natural polymers such as tragacanth, alginate, dextran, pullulan, hyaluronic acid, gelatin and chitosan can be potential candidates for this purpose. In this research, insulin particles were prepared by the inclusion of insulin into a tragacanth hydrogel. The effect of the pH and concentration relationship involving polyelectrolytes offering individual particle size and zeta potential was assessed by zetasizer and scanning electron microscopy (SEM). Insulin–tragacanth interactions at varying pH (3.7, 4.3, 4.6, or 6), and concentration (0.1%, 0.5%, or 1% w/w) were evaluated by differential scanning calorimetry (DSC) and ATR Fourier transform infrared (ATR-FTIR) analysis. Individual and smaller particles, approximately 800 nm, were acquired at pH 4.6 with 0.5% of tragacanth. The acid gelation test indicated that insulin could be entrapped in the physical hydrogel of tragacanth. DSC thermograms of insulin–tragacanth showed shifts on the same unloaded tragacanth peaks and suggested polyelectrolyte–protein interactions at a pH close to 4.3–4.6. FTIR spectra of tragacanth–insulin complexes exhibited amide absorption bands featuring in the protein spectra and revealed the creation of a new chemical substance. PMID:29304023

  5. Effective Drug Delivery in Diffuse Intrinsic Pontine Glioma: A Theoretical Model to Identify Potential Candidates

    Directory of Open Access Journals (Sweden)

    Fatma E. El-Khouly

    2017-10-01

    Full Text Available Despite decades of clinical trials for diffuse intrinsic pontine glioma (DIPG, patient survival does not exceed 10% at two years post-diagnosis. Lack of benefit from systemic chemotherapy may be attributed to an intact bloodbrain barrier (BBB. We aim to develop a theoretical model including relevant physicochemical properties in order to review whether applied chemotherapeutics are suitable for passive diffusion through an intact BBB or whether local administration via convection-enhanced delivery (CED may increase their therapeutic potential. Physicochemical properties (lipophilicity, molecular weight, and charge in physiological environment of anticancer drugs historically and currently administered to DIPG patients, that affect passive diffusion over the BBB, were included in the model. Subsequently, the likelihood of BBB passage of these drugs was ascertained, as well as their potential for intratumoral administration via CED. As only non-molecularly charged, lipophilic, and relatively small sized drugs are likely to passively diffuse through the BBB, out of 51 drugs modeled, only 8 (15%—carmustine, lomustine, erlotinib, vismodegib, lenalomide, thalidomide, vorinostat, and mebendazole—are theoretically qualified for systemic administration in DIPG. Local administration via CED might create more therapeutic options, excluding only positively charged drugs and drugs that are either prodrugs and/or only available as oral formulation. A wide variety of drugs have been administered systemically to DIPG patients. Our model shows that only few are likely to penetrate the BBB via passive diffusion, which may partly explain the lack of efficacy. Drug distribution via CED is less dependent on physicochemical properties and may increase the therapeutic options for DIPG.

  6. Multilayer sodium alginate beads with porous core containing chitosan based nanoparticles for oral delivery of anticancer drug.

    Science.gov (United States)

    Li, Jing; Jiang, Changqing; Lang, Xuqian; Kong, Ming; Cheng, Xiaojie; Liu, Ya; Feng, Chao; Chen, Xiguang

    2016-04-01

    To develop efficient and safe anticancer drug doxorubicin hydrochloride (DOX) delivery system for oral chemotherapy, chitosan based nanoparticles (CS/CMCS-NPs) composed of chitosan (CS) and o-carboxymeymethy chitosan (CMCS) were immobilized in multilayer sodium alginate beads (NPs-M-Beads). Two kinds of NPs-M-Beads, with or without porous core, were respectively prepared by internal or external ionic gelation method. In the small intestine, the intact CS/CMCS-NPs were able to escape from porous-beads and sustained release the loading DOX. In vivo results showed that the DOX could be efficiently absorbed by small intestine of SD rat and the higher concentration of the DOX in major organs of rats were found after oral administration of Porous-Beads, which were about 2-4 folds higher than that of non-porous-beads. These results suggested that the NPs-M-Beads with porous core to be exciting and promising for oral delivery of DOX. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Effect of Zeta Potential on the Properties of Nano-Drug Delivery ...

    African Journals Online (AJOL)

    Zeta potential is a scientific term for electrokinetic potential in colloidal systems which has a major effect on the various properties of nano-drug delivery systems. Presently, colloidal nano-carriers are growing at a remarkable rate owing to their strong potential for overcoming old challenges such as poor drug solubility and ...

  8. Synthesis and characterization of insulin/zirconium phosphate@TiO2 hybrid composites for enhanced oral insulin delivery applications.

    Science.gov (United States)

    Safari, Mostafa; Kamari, Younes; Ghiaci, Mehran; Sadeghi-Aliabadi, Hojjat; Mirian, Mina

    2017-05-01

    In this work, a series of composites of insulin (Ins)/zirconium phosphate (ZrP) were synthesized by intercalation method, then, these composites were coated with TiO 2 by sol-gel method to prepare Ins/ZrP@TiO 2 hybrid composites and the drug release of the composites was investigated by using UV-Vis spectroscopy. Ins/ZrP (10, 30, 60 wt%) composites were prepared by intercalation of insulin into the ZrP layers in water. Then Ins/ZrP composites were coated with different amounts of TiO 2 (30, 50, 100 wt %) by using titanium tetra n-butoxide, as precursor. Formation of intercalated Ins/ZrP and Ins/ZrP@TiO 2 hybrid composites was characterized by FT-IR, FE-SEM, BET and XRD analysis. Zeta potential of the optimized Ins/ZrP@TiO 2 hybrid composite was determined -27.2 mV. Cytotoxic effects of the optimized Ins/ZrP@TiO 2 hybrid composite against HeLa and Hek293T cell lines were evaluated using MTT assay and the results showed that designed drug delivery system was not toxic in biological environment. Compared to the Ins/ZrP composites, incorporation of TiO 2 coating enhanced the drug entrapment considerably, and reduced the drug release. The Ins/ZrP composites without TiO 2 coating released the whole drug after 30 min in pH 7.4 (phosphate buffer solution) while the TiO 2 -coated composites released the entrapped drug after 20 h. In addition to increasing the shelf life of hormone, this nanoencapsulation and nanocoating method can convert the insulin utilization from injection to oral and present a painless and more comfortable treatment for diabetics.

  9. Multilayer encapsulated mesoporous silica nanospheres as an oral sustained drug delivery system for the poorly water-soluble drug felodipine

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Liang [Department of Pharmaceutics, Shenyang Pharmaceutical University, P.O. Box 32, Liaoning Province, Shenyang 110016 (China); Sun, Hongrui [English Teaching Department, School of Basic Courses, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016 (China); Zhao, Qinfu; Han, Ning; Bai, Ling; Wang, Ying; Jiang, Tongying [Department of Pharmaceutics, Shenyang Pharmaceutical University, P.O. Box 32, Liaoning Province, Shenyang 110016 (China); Wang, Siling, E-mail: silingwang@syphu.edu.cn [Department of Pharmaceutics, Shenyang Pharmaceutical University, P.O. Box 32, Liaoning Province, Shenyang 110016 (China)

    2015-02-01

    We used a combination of mesoporous silica nanospheres (MSN) and layer-by-layer (LBL) self-assembly technology to establish a new oral sustained drug delivery system for the poorly water-soluble drug felodipine. Firstly, the model drug was loaded into MSN, and then the loaded MSN were repeatedly encapsulated by chitosan (CHI) and acacia (ACA) via LBL self-assembly method. The structural features of the samples were studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption. The encapsulating process was monitored by zeta-potential and surface tension measurements. The physical state of the drug in the samples was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). The influence of the multilayer with different number of layers on the drug release rate was studied using thermal gravimetric analysis (TGA) and surface tension measurement. The swelling effect and the structure changes of the multilayer were investigated to explore the relationship between the drug release behavior and the state of the multilayer under different pH conditions. The stability and mucosa adhesive ability of the prepared nanoparticles were also explored. After multilayer coating, the drug release rate was effectively controlled. The differences in drug release behavior under different pH conditions could be attributed to the different states of the multilayer. And the nanoparticles possessed good stability and strong mucosa adhesive ability. We believe that this combination offers a simple strategy for regulating the release rate of poorly water-soluble drugs and extends the pharmaceutical applications of inorganic materials and polymers. - Highlights: • A combination of inorganic and organic materials was applied. • Mesoporous silica nanospheres (MSN) were used as drug carriers. • Chitosan and acacia were encapsulated through layer-by-layer self-assembly. • The release rate of the poorly

  10. Enhanced Oral Bioavailability of Pueraria Flavones by a Novel Solid Self-microemulsifying Drug Delivery System (SMEDDS) Dropping Pills.

    Science.gov (United States)

    Guan, Qingxiang; Zhang, Guangyuan; Sun, Shilin; Fan, Hongbo; Sun, Cheng; Zhang, Shaoyuan

    2016-05-01

    To improve bioavailability of pueraria flavones (PF), a self-microemulsifying drug delivery system (SMEDDS) dropping pills composed of PF, Crodamol GTCC, Maisine 35-1, Cremophor RH 40, 1,2-propylene glycol and polyethylene glycol 6000 (PEG6000) was developed. Particle size, zeta potential, morphology and in vitro drug release were investigated, respectively. Pharmacokinetics, bioavailability of PF-SMEDDS dropping pills and commercial Yufengningxin dropping pills were also evaluated and compared in rats. Puerarin treated as the representative component of PF was analyzed. Dynamic light scattering showed the ability of PF-SMEDDS dropping pills to form a nanoemulsion droplet size in aqueous media. The type of media showed no significant effects on the release rate of PF. PF-SMEDDS dropping pills were able to improve the in vitro release rate of PF, and the in vitro release of these dropping pills was significantly faster than that of Yufengningxin dropping pills. There was a dramatic difference between the mean value of t1/2, peak concentration (Cmax), the area of concentration-time curve from 0 to 6 h (AUC0-6 h) of PF-SMEDDS dropping pills and that of commercial Yufengningxin dropping pills. A pharmacokinetic study showed that the bioavailability of PF was greatly enhanced by PF-SMEDDS dropping pills. The value of Cmax and relative bioavailability of PF-SMEDDS dropping pills were dramatically improved by an average of 1.69- and 2.36-fold compared with that of Yufengningxin dropping pills after gavage administration, respectively. It was concluded that bioavailability of PF was greatly improved and that PF-SMEDDS dropping pills might be an encouraging strategy to enhance the oral bioavailability of PF.

  11. Multilayer encapsulated mesoporous silica nanospheres as an oral sustained drug delivery system for the poorly water-soluble drug felodipine

    International Nuclear Information System (INIS)

    Hu, Liang; Sun, Hongrui; Zhao, Qinfu; Han, Ning; Bai, Ling; Wang, Ying; Jiang, Tongying; Wang, Siling

    2015-01-01

    We used a combination of mesoporous silica nanospheres (MSN) and layer-by-layer (LBL) self-assembly technology to establish a new oral sustained drug delivery system for the poorly water-soluble drug felodipine. Firstly, the model drug was loaded into MSN, and then the loaded MSN were repeatedly encapsulated by chitosan (CHI) and acacia (ACA) via LBL self-assembly method. The structural features of the samples were studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption. The encapsulating process was monitored by zeta-potential and surface tension measurements. The physical state of the drug in the samples was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). The influence of the multilayer with different number of layers on the drug release rate was studied using thermal gravimetric analysis (TGA) and surface tension measurement. The swelling effect and the structure changes of the multilayer were investigated to explore the relationship between the drug release behavior and the state of the multilayer under different pH conditions. The stability and mucosa adhesive ability of the prepared nanoparticles were also explored. After multilayer coating, the drug release rate was effectively controlled. The differences in drug release behavior under different pH conditions could be attributed to the different states of the multilayer. And the nanoparticles possessed good stability and strong mucosa adhesive ability. We believe that this combination offers a simple strategy for regulating the release rate of poorly water-soluble drugs and extends the pharmaceutical applications of inorganic materials and polymers. - Highlights: • A combination of inorganic and organic materials was applied. • Mesoporous silica nanospheres (MSN) were used as drug carriers. • Chitosan and acacia were encapsulated through layer-by-layer self-assembly. • The release rate of the poorly

  12. Regular oral screening and vigilance: can it be a potential lifesaver?

    Directory of Open Access Journals (Sweden)

    Madhu Singh Ratre

    2018-01-01

    Full Text Available Acute myeloid leukemia (AML is a malignant neoplasm of myeloid series defined by the presence of immature blast cells (<30% in peripheral circulation. Oral manifestations are the potential indicators of systemic health and disease. Oral cavity is the frequently and early involved sites in AML. Gingival overgrowth due to leukemia is one such condition encountered by periodontists. Hence, understanding, identifying, and correlating oral manifestations with systemic diseases are the ultimate responsibility of every dental clinician because of its lethal and unpredictable course. In the present case, we are discussing an undiagnosed case of AML who presented to us with oral complaints.

  13. Triggers of oral lichen planus flares and the potential role of trigger avoidance in disease management.

    Science.gov (United States)

    Chen, Hannah X; Blasiak, Rachel; Kim, Edwin; Padilla, Ricardo; Culton, Donna A

    2017-09-01

    Many patients with oral lichen planus (OLP) report triggers of flares, some of which overlap with triggers of other oral diseases, including oral allergy syndrome and oral contact dermatitis. The purpose of this study was to evaluate the prevalence of commonly reported triggers of OLP flares, their overlap with triggers of other oral diseases, and the potential role of trigger avoidance as a management strategy. Questionnaire-based survey of 51 patients with biopsy-proven lichen planus with oral involvement seen in an academic dermatology specialty clinic and/or oral pathology clinic between June 2014 and June 2015. Of the participants, 94% identified at least one trigger of their OLP flares. Approximately half of the participants (51%) reported at least one trigger that overlapped with known triggers of oral allergy syndrome, and 63% identified at least one trigger that overlapped with known triggers of oral contact dermatitis. Emotional stress was the most commonly reported trigger (77%). Regarding avoidance, 79% of the study participants reported avoiding their known triggers in daily life. Of those who actively avoided triggers, 89% reported an improvement in symptoms and 70% reported a decrease in the frequency of flares. Trigger identification and avoidance can play a potentially effective role in the management of OLP. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Synthesis and evaluation of mesoporous carbon/lipid bilayer nanocomposites for improved oral delivery of the poorly water-soluble drug, nimodipine.

    Science.gov (United States)

    Zhang, Yanzhuo; Zhao, Qinfu; Zhu, Wufu; Zhang, Lihua; Han, Jin; Lin, Qisi; Ai, Fengwei

    2015-07-01

    A novel mesoporous carbon/lipid bilayer nanocomposite (MCLN) with a core-shell structure was synthesized and characterized as an oral drug delivery system for poorly water-soluble drugs. The objective of this study was to investigate the potential of MCLN-based formulation to modulate the in vitro release and in vivo absorption of a model drug, nimodipine (NIM). NIM-loaded MCLN was prepared by a procedure involving a combination of thin-film hydration and lyophilization. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), specific surface area analysis, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were employed to characterize the NIM-loaded MCLN formulation. The effect of MCLN on cell viability was assessed using the MTT assay. In addition, the oral bioavailability of NIM-loaded MCLN in beagle dogs was compared with that of the immediate-release formulation, Nimotop®. Our results demonstrate that the NIM-loaded MCLN formulation exhibited a typical sustained release pattern. The NIM-loaded MCLN formulation achieved a greater degree of absorption and longer lasting plasma drug levels compared with the commercial formulation. The relative bioavailability of NIM for NIM-loaded MCLN was 214%. MCLN exhibited negligible toxicity. The data reported herein suggest that the MCLN matrix is a promising carrier for controlling the drug release rate and improving the oral absorption of poorly water-soluble drugs.

  15. Lecithin-gold hybrid nanocarriers as efficient and pH selective vehicles for oral delivery of diacerein-In-vitro and in-vivo study.

    Science.gov (United States)

    Javed, Ibrahim; Hussain, Syed Zajif; Shahzad, Atif; Khan, Jahanzeb Muhammad; Ur-Rehman, Habib; Rehman, Mubashar; Usman, Faisal; Razi, Muhammad Tahir; Shah, Muhammad Raza; Hussain, Irshad

    2016-05-01

    We report the synthesis and evaluation of lecithin-gold hybrid nanocarriers for the oral delivery of drugs with improved pharmacokinetics, Au-drug interactive bioactivity and controlled drug releasing behavior at physiological pH inside human body. For this purpose, diacerein, a hydrophobic anti-arthritic drug, was loaded in lecithin NPs (LD NPs), which were further coated by Au NPs either by in-situ production of Au NPs on LD NPs or by employing pre-synthesized Au NPs. All LDAu NPs were found to release drug selectively at the physiological pH of 7.4 and showed 2.5 times increase in the oral bioavailability of diacerein. Pharmacological efficacy was significantly improved i.e., greater than the additive effect of diacerein and Au NPs alone. LDAu NPs started suppressing inflammation at first phase, whereas LD NPs showed activity in the second phase of inflammation. These results indicate the interaction of Au NPs with prostaglandins and histaminic mediators of first phase of carrageenan induced inflammation. Acute toxicity study showed no hepatic damage but the renal toxicity parameters were close to the upper safety limits. Toxicity parameters were dependent on surface engineering of LDAu NPs. Apart from enhancing the oral bioavailability of hydrophobic drugs and improving their anti-inflammatory activity, these hybrid nanocarriers may have potential applications in gold-based photothermal therapy and the tracing of inflammation at atherosclerotic and arthritic site. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. The effect of dentifrice quantity and toothbrushing behaviour on oral delivery and retention of fluoride in vivo.

    Science.gov (United States)

    Creeth, Jonathan; Zero, Domenick; Mau, Melissa; Bosma, Mary Lynn; Butler, Andrew

    2013-12-01

    While toothpaste F(-) concentration and rinsing regimen have well-characterised impacts on fluoride's effectiveness, other aspects of brushing regimen have much less well-established effects, in particular, dentifrice quantity and brushing duration. An in vivo study (n = 42) of oral fluoride delivery (i.e. oral disposition post-brushing), and retention (i.e. concentration of F(-) in saliva post-brushing, a known efficacy predictor), was performed to compare effects observed with those of dentifrice F(-) concentration and rinsing regimen. Subjects brushed with a NaF-silica dentifrice (Aquafresh Advanced, 1,150 ppm F(-) ) or a control dentifrice (250 ppm F(-) , same base), for 45, 60, 120 or 180 seconds with 0.5 or 1.5 g dentifrice, and rinsed with 15 ml water once or three times in a cross-over design. The F(-) concentration was measured in post-brushing expectorate, rinse and toothbrush washing samples, and in saliva between 5-120 minutes after brushing. Using 1.5 g versus 0.5 g dentifrice increased F(-) in all samples: oral retention of F(-) was almost doubled by this increase. Increasing duration of brushing had more complex effects. The amount of F(-) in the expectorate increased but decreased in both rinse and toothbrush washing samples. Oral F(-) retention increased, but only in the period 30-120 minutes after brushing. Over the ranges investigated, the order of importance on oral F(-) retention was: dentifrice F(-) concentration > quantity > rinsing regimen > brushing duration. Hence, increasing dentifrice quantity and, to a lesser extent, the duration of brushing, can elevate oral fluoride post-brushing. Evidence is accumulating that the importance of these variables to fluoride efficacy may have been underestimated. © 2013 FDI World Dental Federation.

  17. Chitosan-sodium lauryl sulfate nanoparticles as a carrier system for the in vivo delivery of oral insulin.

    Science.gov (United States)

    Elsayed, Amani; Al-Remawi, Mayyas; Qinna, Nidal; Farouk, Asim; Al-Sou'od, Khaldoun A; Badwan, Adnan A

    2011-09-01

    The present work explores the possibility of formulating an oral insulin delivery system using nanoparticulate complexes made from the interaction between biodegradable, natural polymer called chitosan and anionic surfactant called sodium lauryl sulfate (SLS). The interaction between chitosan and SLS was confirmed by Fourier transform infrared spectroscopy. The nanoparticles were prepared by simple gelation method under aqueous-based conditions. The nanoparticles were stable in simulated gastric fluids and could protect the encapsulated insulin from the GIT enzymes. Additionally, the in vivo results clearly indicated that the insulin-loaded nanoparticles could effectively reduce the blood glucose level in a diabetic rat model. However, additional formulation modifications are required to improve insulin oral bioavailability.

  18. Combining two technologies: multifunctional polymers and self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration.

    Science.gov (United States)

    Sakloetsakun, Duangkamon; Dünnhaupt, Sarah; Barthelmes, Jan; Perera, Glen; Bernkop-Schnürch, Andreas

    2013-10-01

    The aim of the study is to develop a self-nanoemulsifying drug delivery system (SNEDDS) based on thiolated chitosan for oral insulin administration. The preparations were characterized by particle size, entrapment efficiency, stability and drug release. Serum insulin concentrations were determined after oral administration of all formulations. Insulin SNEDDS formulation was served as control. The optimized SNEDDS consists of 65% (w/w) miglyol 840, 25% (w/w) cremophor EL, 10% (w/w) co-solvents (a mixture of DMSO and glycerol). The formulations in the presence or absence of insulin (5mg/mL) were spherical with the size range between 80 and 160 nm. Entrapment efficiency of insulin increased significantly when the thiolated chitosan was employed (95.14±2.96%), in comparison to the insulin SNEDDS (80.38±1.22%). After 30 min, the in vitro release profile of insulin from the nanoemulsions was markedly increased compared to the control. In vivo results showed that insulin/thiolated chitosan SNEDDS displayed a significant increase in serum insulin (p-value=0.02) compared to oral insulin solution. A new strategy to combine SNEDDS and thiolated chitosan described in the study would therefore be a promising and innovative approach to improve oral bioavailability of insulin. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  19. Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system.

    Science.gov (United States)

    Chen, Zhi-Qiang; Liu, Ying; Zhao, Ji-Hui; Wang, Lan; Feng, Nian-Ping

    2012-01-01

    Indirubin, isolated from the leaves of the Chinese herb Isatis tinctoria L, is a protein kinase inhibitor and promising antitumor agent. However, the poor water solubility of indirubin has limited its application. In this study, a supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) was developed to improve the oral bioavailability of indirubin. A prototype S-SMEDDS was designed using solubility studies and phase diagram construction. Precipitation inhibitors were selected from hydrophilic polymers according to their crystallization-inhibiting capacity through in vitro precipitation tests. In vitro release of indirubin from S-SMEDDS was examined to investigate its likely release behavior in vivo. The in vivo bioavailability of indirubin from S-SMEDDS and from SMEDDS was compared in rats. The prototype formulation of S-SMEDDS comprised Maisine™ 35-1:Cremophor(®) EL:Transcutol(®) P (15:40:45, w/w/w). Polyvinylpyrrolidone K17, a hydrophilic polymer, was used as a precipitation inhibitor based on its better crystallization-inhibiting capacity compared with polyethylene glycol 4000 and hydroxypropyl methylcellulose. In vitro release analysis showed more rapid drug release from S-SMEDDS than from SMEDDS. In vivo bioavailability analysis in rats indicated that improved oral absorption was achieved and that the relative bioavailability of S-SMEDDS was 129.5% compared with SMEDDS. The novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of indirubin in rats. The results suggest that S-SMEDDS is a superior means of oral delivery of indirubin.

  20. 3D printed multi-compartment capsular devices for two-pulse oral drug delivery.

    Science.gov (United States)

    Maroni, A; Melocchi, A; Parietti, F; Foppoli, A; Zema, L; Gazzaniga, A

    2017-12-28

    In the drug delivery area, versatile therapeutic systems intended to yield customized combinations of drugs, drug doses and release kinetics have drawn increasing attention, especially because of the advantages that personalized pharmaceutical treatments would offer. In this respect, a previously proposed capsular device able to control the release performance based on its design and composition, which could extemporaneously be filled, was improved to include multiple separate compartments so that differing active ingredients or formulations may be conveyed. The compartments, which may differ in thickness and composition, resulted from assembly of two hollow halves through a joint also acting as a partition. The systems were manufactured by fused deposition modeling (FDM) 3D printing, which holds special potential for product personalization, and injection molding (IM) that would enable production on a larger scale. Through combination of compartments having wall thickness of 600 or 1200μm, composed of promptly soluble, swellable/erodible or enteric soluble polymers, devices showing two-pulse release patterns, consistent with the nature of the starting materials, were obtained. Systems fabricated using the two techniques exhibited comparable performance, thus proving the prototyping ability of FDM versus IM. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Potentiality of the Usage of Compressed Natural Gas for Competitiveness in Service Delivery Industries

    Directory of Open Access Journals (Sweden)

    Gazi Mohammad Hasan Jamil

    2014-08-01

    Full Text Available Abstract. With the rising costs of gasoline, many vehicle owners are looking for alternatives of it. Compressed natural gas (CNG has been tested for this very purpose in some countries and found as a better alternative so far. CNG comes from country’s natural resources and it is clean and less costly to use. This paper is mainly an analysis of the potential benefits of using natural gas as a transportation fuel by the service delivery industries. It will examine CNG’s potential contribution in reducing delivery and vehicle maintenance cost, saving money in the long run projects, improving fuel efficiency, enhancing physical safety and assuring environment friendly emissions of carbon monoxide or reactive gases for the service delivery industries.Keywords: Compressed natural gas (CNG, Service Delivery, Fossil fuel, Global warming, Competitiveness

  2. Transdermal delivery of gentamicin using dissolving microneedle arrays for potential treatment of neonatal sepsis.

    Science.gov (United States)

    González-Vázquez, Patricia; Larrañeta, Eneko; McCrudden, Maelíosa T C; Jarrahian, Courtney; Rein-Weston, Annie; Quintanar-Solares, Manjari; Zehrung, Darin; McCarthy, Helen; Courtenay, Aaron J; Donnelly, Ryan F

    2017-11-10

    Neonatal infections are a leading cause of childhood mortality in low-resource settings. World Health Organization guidelines for outpatient treatment of possible serious bacterial infection (PSBI) in neonates and young infants when referral for hospital treatment is not feasible include intramuscular gentamicin (GEN) and oral amoxicillin. GEN is supplied as an aqueous solution of gentamicin sulphate in vials or ampoules and requires health care workers to be trained in dose calculation or selection of an appropriate dose based on the patient's weight band and to have access to safe injection supplies and appropriate sharps disposal. A simplified formulation, packaging, and delivery method to treat PSBI in low-resource settings could decrease user error and expand access to lifesaving outpatient antibiotic treatment for infants with severe infection during the neonatal period. We developed dissolving polymeric microneedles (MN) arrays to deliver GEN transdermally. MN arrays were produced from aqueous blends containing 30% (w/w) of GEN and two polymers approved by the US Food and Drug Administration: sodium hyaluronate and poly(vinylpyrrolidone). The arrays (19×19 needles and 500μm height) were mechanically strong and were able to penetrate a skin simulant to a depth of 378μm. The MN arrays were tested in vitro using a Franz Cell setup delivering approximately 4.45mg of GEN over 6h. Finally, three different doses (low, medium, and high) of GEN delivered by MN arrays were tested in an animal model. Maximum plasma levels of GEN were dose-dependent and ranged between 2 and 5μg/mL. The time required to reach these levels post-MN array application ranged between 1 and 6h. This work demonstrated the potential of dissolving MN arrays to deliver GEN transdermally at therapeutic levels in vivo. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration.

    Science.gov (United States)

    Cherniakov, Irina; Izgelov, Dvora; Barasch, Dinorah; Davidson, Elyad; Domb, Abraham J; Hoffman, Amnon

    2017-11-28

    Nowadays, therapeutic indications for cannabinoids, specifically Δ 9 -tetrahydrocannabinol (THC) and Cannabidiol (CBD) are widening. However, the oral consumption of the molecules is very limited due to their highly lipophilic nature that leads to poor solubility at the aqueous environment. Additionally, THC and CBD are prone to extensive first pass mechanisms. These absorption obstacles render the molecules with low and variable oral bioavailability. To overcome these limitations we designed and developed the advanced pro-nanolipospheres (PNL) formulation. The PNL delivery system is comprised of a medium chain triglyceride, surfactants, a co-solvent and the unique addition of a natural absorption enhancer: piperine. Piperine was selected due to its distinctive inhibitory properties affecting both Phase I and Phase II metabolism. This constellation self emulsifies into nano particles that entrap the cannabinoids and the piperine in their core and thus improve their solubility while piperine and the other PNL excipients inhibit their intestinal metabolism. Another clear advantage of the formulation is that its composition of materials is approved for human consumption. The safe nature of the excipients enabled their direct evaluation in humans. In order to evaluate the pharmacokinetic profile of the THC-CBD-piperine-PNL formulation, a two-way crossover, single administration clinical study was conducted. The trial comprised of 9 healthy volunteers under fasted conditions. Each subject received a THC-CBD (10.8mg, 10mg respectively) piperine (20mg)-PNL filled capsule and an equivalent dose of the oromucosal spray Sativex® with a washout period in between treatments. Single oral administration of the piperine-PNL formulation resulted in a 3-fold increase in Cmax and a 1.5-fold increase in AUC for THC when compared to Sativex®. For CBD, a 4-fold increase in Cmax and a 2.2-fold increase in AUC was observed. These findings demonstrate the potential this formulation has

  4. The human oral metaproteome reveals potential biomarkers for caries disease

    DEFF Research Database (Denmark)

    Belda-Ferre, Pedro; Williamson, James; Simón-Soro, Áurea

    2015-01-01

    metabolism and immune response. We applied multivariate analysis in order to find the minimum set of proteins that better allows discrimination of healthy and caries-affected dental plaque samples, detecting seven bacterial and five human protein functions that allow determining the health status......Tooth decay is considered the most prevalent human disease worldwide. We present the first metaproteomic study of the oral biofilm, using different mass spectrometry approaches that have allowed us to quantify individual peptides in healthy and caries-bearing individuals. A total of 7771 bacterial...... and 853 human proteins were identified in 17 individuals, which provide the first available protein repertoire of human dental plaque. Actinomyces and Coryneybacterium represent a large proportion of the protein activity followed by Rothia and Streptococcus. Those four genera account for 60-90% of total...

  5. Antimicrobial potential of Casearia sylvestris against oral bacteria

    Directory of Open Access Journals (Sweden)

    Amanda Henriques CAVALHEIRO

    Full Text Available Abstract Aim The aim of this study was to obtain Casearia sylvestris leave extracts by different extractive methods, including the obtention of essential oil, in order to compare their antimicrobial activities to conventional mouthwash chlorhexidine against oral bacteria. Material and method For this evaluation, extracts from the leaves were obtained by different methods of extraction (infusion, decoction, maceration and percolation using different solvent systems: water 100%, ethanol 100%, methanol 100%, water: ethanol 3:7; water: ethanol 7:3; water: methanol 7:3 and water: methanol 3:7. The essential oil, which corresponds to a volatile fraction, was obtained by hydrodistillation using Clevenger modified apparatus. The microdilution broth method was used to determine the values of minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC for the following microorganisms: Streptococcus mutans ATCC 25175, S. mitis ATCC 49456, S. sanguinis ATCC 10556, S. salivarius ATCC 25975, Lactobacillus casei ATCC 11578 and Enterococcus faecalis ATCC4082. Chlorhexidine gluconate was used as a positive control. Result All extracts evaluated in the used protocol displayed MIC values higher than 400 µg/mL and few showed bactericidal activity. The antimicrobial activity of essential oil was higher than the activity of the extracts, and the best minimum inhibitory concentration and minimum bactericidal concentration values were obtained against L. casei (MIC of 0.023 µg/mL and MBC of 0.046 µg/mL and S. mutans (MIC of 25 µg/mL and MBC of 50 µg/mL, respectively. Conclusion The essential oil of Casearia sylvestris has significant antimicrobial activity against oral microorganisms.

  6. ORAL COLON TARGETED DRUG DELIVERY SYSTEM: A REVIEW ON CURRENT AND NOVEL PERSPECTIVES

    OpenAIRE

    Asija Rajesh; Chaudhari Bharat; Asija Sangeeta

    2012-01-01

    Small intestine is mostly the site for drug absorption but in some cases the drug needs to be targeted to colon due to some factors like local colonic disease, degradation related conditions, delayed release of drugs, systemic delivery of protein and peptide drugs etc. Colon targeted drug delivery is important and relatively new concept for the absorption of drugs because it offers almost neutral pH and long residence time, thereby increasing the drug absorption. Colon has proved to be a site...

  7. Lyophilized mucoadhesive-dendrimer enclosed matrix tablet for extended oral delivery of albendazole.

    Science.gov (United States)

    Mansuri, Shakir; Kesharwani, Prashant; Tekade, Rakesh Kumar; Jain, Narendra Kumar

    2016-05-01

    Dendrimers are multifunctional carriers widely employed for delivering drugs in a variety of disease conditions including HIV/AIDS and cancer. Albendazole (ABZ) is a commonly used anthelmintic drug in human as well as veterinary medicine. In this investigation, ABZ was formulated as a "muco-dendrimer" based sustained released tablet. The mucoadhesive complex was synthesized by anchoring chitosan to fifth generation PPI dendrimer (Muco-PPI) and characterized by UV, FTIR, (1)H NMR spectroscopy and electron microscopy. ABZ was entrapped inside Muco-PPI followed by lyophilization and tableting as matrix tablet. A half-life (t1/2) of 8.06±0.15, 8.17±0.47, 11.04±0.73, 11.49±0.92, 12.52±1.04 and 16.9±1.18h was noted for ABZ (free drug), conventional ABZ tablet (F1), conventional ABZ matrix tablet (F2), PPI-ABZ complex, PPI-ABZ matrix tablet (F3) and Muco-PPI-ABZ matrix tablet (F4), respectively. Thus the novel mucoadhesive-PPI based formulation of ABZ (F4) increased the t1/2 of ABZ significantly by almost twofold as compared to the administration of free drug. The in vivo drug release data showed that the Muco-PPI based formulations have a significantly higher Cmax (2.40±0.02μg/mL) compared with orally administered free ABZ (0.19±0.07μg/mL) as well as conventional tablet (0.20±0.05μg/mL). In addition, the Muco-PPI-ABZ matrix tablet displayed increased mean residence time (MRT) and is therefore a potential candidate to appreciably improve the pharmacokinetic profile of ABZ. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Sublingual Delivery of Frovatriptan: An Indication of Potential Alternative Route

    Science.gov (United States)

    Verma, Surajpal; Prasad, Shyam Baboo

    2014-01-01

    Frovatriptan, a 5-HT1B and 5-HT1D receptor agonist, is used for the treatment of acute migraine attack. This molecule is classified into second line therapy because of its slow onset of action (peak response obtained after 4 hours of administration) and low bioavailability (25%). Moreover, its therapy is the most costly among all triptans. Attempt has been made in present work to suggest a way out to fasten its onset of action and to enhance its bioavailability. Prepared tablets were evaluated by physicochemical tests, in vitro permeation studies, ex vivo permeation studies, and histopathological studies. Suitable mathematical calculations were performed to calculate the minimum amount of bioavailability that could be enhanced. Tablets containing chitosan (5% w/w) were found to give optimum results. Prepared tablets can double the bioavailability of frovatriptan and can initiate its response within 10 minutes of its administration. Suggestive alternative has the potential to increase the efficacy of frovatriptan for treating acute migraine attack. PMID:27433492

  9. Comparison of different zeolite framework types as carriers for the oral delivery of the poorly soluble drug indomethacin.

    Science.gov (United States)

    Karavasili, Christina; Amanatiadou, Elsa P; Kontogiannidou, Eleni; Eleftheriadis, Georgios K; Bouropoulos, Nikolaos; Pavlidou, Eleni; Kontopoulou, Ioanna; Vizirianakis, Ioannis S; Fatouros, Dimitrios G

    2017-08-07

    Microporous zeolites of distinct framework types, textural properties and crystal morphologies namely BEA, ZSM and NaX, have been employed as carriers to assess their effect on modulating the dissolution behavior of a BCS II model drug (indomethacin). Preparation of the loaded carriers via the incipient wetness method induced significant drug amorphization for the BEA and NaX samples, as well as high drug payloads. The stability of the amorphous drug content was retained after stressing test evaluation of the porous carriers. The dissolution profile of loaded indomethacin was evaluated in simulated gastric fluid (pH 1.2) and simulated intestinal fluids FaSSIF (fasted) and FeSSIF (fed state) conditions and was found to be dependent on the aluminosilicate ratio of the zeolites and the degree of crystalline drug content. The feasibility of the zeolitic particles as oral drug delivery systems was appraised with cytocompatibility and cellular toxicity studies in Caco-2 cultures in a time- and dose-dependent manner by means of the MTT assay and flow cytometry analysis, respectively. Intracellular accumulation of the zeolite particles was observed with no apparent cytotoxic effects at the lower concentrations tested, rendering such microporous zeolites pertinent candidates in oral drug delivery applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Self-Nanoemulsifying Lyophilized Tablets for Flash Oral Transmucosal Delivery of Vitamin K: Development and Clinical Evaluation.

    Science.gov (United States)

    El-Say, Khalid M; Ahmed, Tarek A; Ahmed, Osama A A; Hosny, Khaled M; Abd-Allah, Fathy I

    2017-09-01

    Owing to limited solubility, vitamin K undergoes low bioavailability with large inter-individual variability after oral administration. This article aimed to prepare self-nanoemulsifying lyophilized tablets (SNELTs) for the flash oral transmucosal delivery of vitamin K. Twenty-one formulae of vitamin K self-nanoemulsifying drug delivery systems (SNEDDS) were prepared using different concentrations of vitamin K, Labrasol, and Transcutol according to mixture design. The SNEDDS was loaded on porous carriers and formulated as lyophilized tablets. The release profile and the pharmacokinetic parameters of vitamin K SNELTs were evaluated in comparison with commercial tablets and ampoules on human volunteers. Results revealed that the optimized SNEDDS showed the smallest and most stable nanoemulsion globules. SNELTs were prepared successfully and showed substantial superiority drug release compared with the commercial tablets. Interestingly, SNELTs enhanced both rate and extent of vitamin K absorption as well as relative bioavailability (169.67%) in healthy subjects compared with the commercial tablets. SNELTs revealed promising no significant difference in the area under the curve compared with the commercial intramuscular injection. SNELTs enhanced dissolution and bioavailability that expected to have the strong impact on the efficiency of vitamin K in the prophylaxis and treatment of bleeding disorders in patients with hepatic dysfunction. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. pH-responsive thiolated chitosan nanoparticles for oral low-molecular weight heparin delivery: in vitro and in vivo evaluation.

    Science.gov (United States)

    Fan, Bo; Xing, Yang; Zheng, Ying; Sun, Chuan; Liang, Guixian

    2016-01-01

    The aim of present study was to investigate a pH-responsive and mucoadhesive nanoparticle system for oral bioavailability enhancement of low-molecular weight heparin (LMWH). The thioglycolic acid (TGA) was first covalently attached to chitosan (CS) with 396.97 ± 54.54 μmol thiol groups per gram of polymer and then the nanoparticles were prepared with thiolated chitosan (TCS) and pH-sensitive polymer hydroxypropyl methylcellulose phthalate (HPMCP) by ionic cross-linking method. The obtained nanoparticles were characterized for the shape, particle size, zeta potential, drug entrapment efficiency and loading capacity. In vitro results revealed the acid stability of pH-responsive nanoparticles, which had a significant control over LMWH release and could effectively protect entrapped drugs in simulated gastric conditions. By the attachment of the thiol ligand, an improvement of permeation-enhancing effect on freshly excised carp intestine (1.86-fold improvement) could be found. The mucoadhesive properties were evaluated using fluorescently labeled TCS or CS nanoparticles. As compared with the controls, a significant improvement of mucoadhesion on rat intestinal mucosa was observed in TCS/HPMCP nanoparticles via confocal laser scanning microscopy. The activated partial thromboplastin time (APTT) was significantly prolonged and an increase in the oral bioavailability of LMWH was turned out to be pronounced after oral delivered LMWH-loaded TCS/HPMCP nanoparticles in rats, which suggested enhanced anticoagulant effects and improved absorption of LMWH. In conclusion, pH-responsive TCS/HPMCP nanoparticles hold promise for oral delivery of LMWH.

  12. Investigations on the potential of a low power diode pumped Er:YAG laser system for oral surgery

    Science.gov (United States)

    Stock, Karl; Wurm, Holger; Hausladen, Florian; Wagner, Sophia; Hibst, Raimund

    2015-02-01

    Flash lamp pumped Er:YAG-lasers are used in clinical practice for dental applications successfully. As an alternative, several diode pumped Er:YAG laser systems (Pantec Engineering AG) become available, with mean laser power of 2W, 15W, and 30W. The aim of the presented study is to investigate the potential of the 2W Er:YAG laser system for oral surgery. At first an appropriate experimental set-up was realized with a beam delivery and both, a focusing unit for non-contact tissue cutting and a fiber tip for tissue cutting in contact mode. In order to produce reproducible cuts, the samples (porcine gingiva) were moved by a computer controlled translation stage. On the fresh samples cutting depth and quality were determined by light microscopy. Afterwards histological sections were prepared and microscopically analyzed regarding cutting depth and thermal damage zone. The experiments show that low laser power ≤ 2W is sufficient to perform efficient oral soft tissue cutting with cut depth up to 2mm (sample movement 2mm/s). The width of the thermal damage zone can be controlled by the irradiation parameters within a range of about 50μm to 110μm. In general, thermal injury is more pronounced using fiber tips in contact mode compared to the focused laser beam. In conclusion the results reveal that even the low power diode pumped Er:YAG laser is an appropriate tool for oral surgery.

  13. Exploring the potential of laser capture microdissection technology in integrated oral biosciences.

    Science.gov (United States)

    Thennavan, A; Sharma, M; Chandrashekar, C; Hunter, K; Radhakrishnan, R

    2017-09-01

    Laser capture microdissection (LCM) is a high-end research and diagnostic technology that helps in obtaining pure cell populations for the purpose of cell- or lesion-specific genomic and proteomic analysis. Literature search on the application of LCM in oral tissues was made through PubMed. There is ample evidence to substantiate the utility of LCM in understanding the underlying molecular mechanism involving an array of oral physiological and pathological processes, including odontogenesis, taste perception, eruptive tooth movement, oral microbes, and cancers of the mouth and jaw tumors. This review is aimed at exploring the potential application of LCM in oral tissues as a high-throughput tool for integrated oral sciences. The indispensable application of LCM in the construction of lesion-specific genomic libraries with emphasis on some of the novel molecular markers thus discovered is also highlighted. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Multidisciplinary Optimization of Oral Chemotherapy Delivery at the University of Wisconsin Carbone Cancer Center.

    Science.gov (United States)

    Mulkerin, Daniel L; Bergsbaken, Jason J; Fischer, Jessica A; Mulkerin, Mary J; Bohler, Aaron M; Mably, Mary S

    2016-10-01

    Use of oral chemotherapy is expanding and offers advantages while posing unique safety challenges. ASCO and the Oncology Nursing Society jointly published safety standards for administering chemotherapy that offer a framework for improving oral chemotherapy practice at the University of Wisconsin Carbone Cancer Center. With the goal of improving safety, quality, and uniformity within our oral chemotherapy practice, we conducted a gap analysis comparing our practice against ASCO/Oncology Nursing Society guidelines. Areas for improvement were addressed by multidisciplinary workgroups that focused on education, workflows, and information technology. Recommendations and process changes included defining chemotherapy, standardizing patient and caregiver education, mandating the use of comprehensive electronic order sets, and standardizing documentation for dose modification. Revised processes allow pharmacists to review all orders for oral chemotherapy, and they support monitoring adherence and toxicity by using a library of scripted materials. Between August 2015 and January 2016, revised processes were implemented across the University of Wisconsin Carbone Cancer Center clinics. The following are key performance indicators: 92.5% of oral chemotherapy orders (n = 1,216) were initiated within comprehensive electronic order sets (N = 1,315), 89.2% compliance with informed consent was achieved, 14.7% of orders (n = 193) required an average of 4.4 minutes review time by the pharmacist, and 100% compliance with first-cycle monitoring of adherence and toxicity was achieved. We closed significant gaps between institutional practice and published standards for our oral chemotherapy practice and experienced steady improvement and sustainable performance in key metrics. We created an electronic definition of oral chemotherapies that allowed us to leverage our electronic health records. We believe our tools are broadly applicable.

  15. Efficacy of light based detection systems for early detection of oral cancer and oral potentially malignant disorders: Systematic review.

    Science.gov (United States)

    Nagi, R; Reddy-Kantharaj, Y-B; Rakesh, N; Janardhan-Reddy, S; Sahu, S

    2016-07-01

    Earlier detection of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) is essential for dental professionals to improve patient survival rates. The aim of this systematic review is to to evaluate the effectiveness of devices that utilise the principles of chemiluminescence and tissue autofluorescence as adjuncts in the detection of OSCC and OPMD. The electronic retrieval systems and databases searched for relevant articles were PubMed [MEDLINE] and Science direct. The search was for limited articles published in English or with an English abstract and articles published during the period from January 2005 to April 2014. Clinical trials utilized ViziLite, Microlux TM/DL and Visual Enhanced Light scope (VELscope) for early detection of OPMD and OSCC. Twenty primary studies published satisfied our criteria for selection - 10 utilised chemiluminescence and 10 tissue autofluorescence. Senstivity of Vizilite for detecting OSCC nad OPMD ranged from 77.1 % to 100% and specificity was low that ranged from 0% to 27.8%.Most have shown that chemiluminescence increases the brightness and margins of oral mucosal white lesions and thus assist in identification of mucosal lesions not considered under Conventional visual examination. However, it preferentially detects leukoplakia and may fail to spot red patches. Clinical trials demonstrated that sensitivity of VELscope in detecting malignancy and OPMD ranged from 22 % to 100 % and specificity ranged from 16 % to 100%. Most studies concluded that VELscope can help the experienced clinician to find oral precursor malignant lesions. But it couldnot differentiate between dysplasia and benign inflammatory conditions. Both devices are simple, non-invasive test of the oral mucosa but are suited for clinicians with sufficient experience and training. More clinical trials in future should be conducted to establish optical imaging as an efficacious adjunct tool in early diagnosis of OSCC and OPMD.

  16. Mechanism of enhanced oral absorption of morin by phospholipid complex based self-nanoemulsifying drug delivery system.

    Science.gov (United States)

    Zhang, Jinjie; Li, Jianbo; Ju, Yuan; Fu, Yao; Gong, Tao; Zhang, Zhirong

    2015-02-02

    Phospholipid complex (PLC) based self-nanoemulsifying drug delivery system (PLC-SNEDDS) has been developed for efficient delivery of drugs with poor solubility and low permeability. In the present study, a BCS class IV drug and a P-glycoprotein (P-gp) substrate, morin, was selected as the model drug to elucidate the oral absorption mechanism of PLC-SNEDDS. PLC-SNEDDS was superior to PLC in protecting morin from degradation by intestinal enzymes in vitro. In situ perfusion study showed increased intestinal permeability by PLC was duodenum-specific. In contrast, PLC-SNEDDS increased morin permeability in all intestinal segments and induced a change in the main absorption site of morin from colon to ileum. Moreover, ileum conducted the lymphatic transport of PLC-SNEDDS, which was proven by microscopic intestinal visualization of Nile red labeled PLC-SNEDDS and lymph fluids in vivo. Low cytotoxicity and increased Caco-2 cell uptake suggested a safe and efficient delivery of PLC-SNEDDS. The increased membrane fluidity and disrupted actin filaments were closely associated with the increased cell uptake of PLC-SNEDDS. PLC-SNEDDS could be internalized into enterocytes as an intact form in a cholesterol-dependent manner via clathrin-mediated endocytosis and macropinocytosis. The enhanced oral absorption of morin was attributed to the P-gp inhibition by Cremophor RH and the intact internalization of M-PLC-SNEDDS into Caco-2 cells bypassing P-gp recognition. Our findings thus provide new insights into the development of novel nanoemulsions for poorly absorbed drugs.

  17. Screening of Oral Potentially Malignant Disorders Using Exfoliative Cytology: A Diagnostic Modality

    International Nuclear Information System (INIS)

    Kabiraj, A.

    2016-01-01

    Oral exfoliative cytology (OEC) has been implemented in the diagnosis of pathologic lesions for ages. The present study was undertaken to evaluate the cytomorphological features of some of the commonest potentially malignant disorders (leukoplakia, lichen planus, and oral sub mucous fibrosis) through a simple procedure and illustrate its importance in mass screening. Materials and Method. A total of 160 subjects with 25-50 years of age were included in the study. Among them, 40 were clinically diagnosed with oral leukoplakia, 40 were diagnosed with oral lichen planus, 40 were diagnosed with oral sub mucous fibrosis, and 40 were in the control group. The prepared smears were subjected to Papanicolaou stain and analyzed microscopically for the evaluation of the cytomorphological features. Results and Discussion. When analyzed microscopically, 36 (90%) out of the 40 oral leukoplakic lesions showed Class II cytological features whereas 4 (10%) revealed Class I features. Among 40 patients with oral lichen planus, 26 (65%) showed Class II features while the remaining 14 (35%) revealed Class I features. In 40 subjects with oral sub mucous fibrosis, 32 (80%) showed Class II features while the other 8 (20%) showed Class I features. All the 40 control subjects showed Class I features. Thus, OEC can be widely advocated as an addition to clinical conclusion and an adjunct to biopsy.

  18. Amine functionalized cubic mesoporous silica nanoparticles as an oral delivery system for curcumin bioavailability enhancement

    Science.gov (United States)

    Budi Hartono, Sandy; Hadisoewignyo, Lannie; Yang, Yanan; Meka, Anand Kumar; Antaresti; Yu, Chengzhong

    2016-12-01

    In the present work, a simple method was used to develop composite curcumin-amine functionalized mesoporous silica nanoparticles (MSN). The nanoparticles were used to improve the bioavailability of curcumin in mice through oral administration. We investigated the effect of particle size on the release profile, solubility and oral bioavailability of curcumin in mice, including amine functionalized mesoporous silica micron-sized-particles (MSM) and MSN (100-200 nm). Curcumin loaded within amine functionalized MSN (MSN-A-Cur) had a better release profile and a higher solubility compared to amine MSM (MSM-A-Cur). The bioavailability of MSN-A-Cur and MSM-A-Cur was considerably higher than that of ‘free curcumin’. These results indicate promising features of amine functionalized MSN as a carrier to deliver low solubility drugs with improved bioavailability via the oral route.

  19. Prognostic potential of n-cadherin in oral squamous cell carcinoma via immunohistochemical methods

    International Nuclear Information System (INIS)

    Chandolia, B.; Arora, M.; Rajliwal, P.

    2017-01-01

    To assess the prognostic potential for N-cadherin in oral squamous cell carcinoma and oral epithelial dysplasia. Study Design: A cross-sectional study, analytical study. Place and Duration of Study: Maharishi Markandeshwar College of Dental Science Research (MMCDSR), Ambala, India, from 2011 to 2014. Methodology: Immunohistochemistry was used to observe the N-cadherin expression in 100 cases having epithelium with normal oral mucosa, oral epithelial dysplastic lesions and oral squamous cell carcinoma (OSCC). For statistical significance, SPSS 13.0 was used to calculate the data by Mann-Whitney and Kruskal-Wallis tests. Results: In OSCC, N-cadherin expression was more evident than in oral epithelial dysplasia followed by the normal oral epithelium that did not show any dysplastic changes (p=0.001). Conversely, N-cadherin expression was not significant among the histological grade of OSCC. Conclusion: N-cadherin can be used as a potential biomarker for early diagnosis of OSCC. However, the N-cadherin expression did not show any correlation with the histological grade of OSCC. (author)

  20. Prognostic Potential of N-Cadherin in Oral Squamous Cell Carcinoma via Immunohistochemical Methods.

    Science.gov (United States)

    Chandolia, Betina; Rajliwal, Jai Parkash; Bajpai, Manas; Arora, Manika

    2017-08-01

    To assess the prognostic potential for N-cadherin in oral squamous cell carcinoma and oral epithelial dysplasia. Across-sectional study, analytical study. Maharishi Markandeshwar College of Dental Science Research (MMCDSR), Ambala, India, from 2011 to 2014. Immunohistochemistry was used to observe the N-cadherin expression in 100 cases having epithelium with normal oral mucosa, oral epithelial dysplastic lesions and oral squamous cell carcinoma (OSCC). For statistical significance, SPSS 13.0 was used to calculate the data by Mann-Whitney and Kruskal-Wallis tests. In OSCC, N-cadherin expression was more evident than in oral epithelial dysplasia followed by the normal oral epithelium that did not show any dysplastic changes (p=0.001). Conversely, N-cadherin expression was not significant among the histological grade of OSCC. N-cadherin can be used as a potential biomarker for early diagnosis of OSCC. However, the N-cadherin expression did not show any correlation with the histological grade of OSCC.

  1. Effective plague vaccination via oral delivery of plant cells expressing F1-V antigens in chloroplasts.

    Science.gov (United States)

    Arlen, Philip A; Singleton, Michael; Adamovicz, Jeffrey J; Ding, Yi; Davoodi-Semiromi, Abdolreza; Daniell, Henry

    2008-08-01

    The chloroplast bioreactor is an alternative to fermentation-based systems for production of vaccine antigens and biopharmaceuticals. We report here expression of the plague F1-V fusion antigen in chloroplasts. Site-specific transgene integration and homoplasmy were confirmed by PCR and Southern blotting. Mature leaves showed the highest level of transgene expression on the third day of continuous illumination, with a maximum level of 14.8% of the total soluble protein. Swiss Webster mice were primed with adjuvant-containing subcutaneous (s.c.) doses of F1-V and then boosted with either adjuvanted s.c. doses (s.c. F1-V mice) or unadjuvanted oral doses (oral F1-V mice). Oral F1-V mice had higher prechallenge serum immunoglobulin G1 (IgG1) titers than s.c. F1-V mice. The corresponding serum levels of antigen-specific IgG2a and IgA were 2 and 3 orders of magnitude lower, respectively. After vaccination, mice were exposed to an inhaled dose of 1.02 x 10(6) CFU of aerosolized Yersinia pestis CO92 (50% lethal dose, 6.8 x 10(4) CFU). All control animals died within 3 days. F1-V given s.c. (with adjuvant) protected 33% of the immunized mice, while 88% of the oral F1-V mice survived aerosolized Y. pestis challenge. A comparison of splenic Y. pestis CFU counts showed that there was a 7- to 10-log reduction in the mean bacterial burden in survivors. Taken together, these data indicate that oral booster doses effectively elicit protective immune responses in vivo. In addition, this is the first report of a plant-derived oral vaccine that protected animals from live Y. pestis challenge, bringing the likelihood of lower-cost vaccines closer to reality.

  2. Combination therapy of potential gene to enhance oral cancer therapeutic effect

    Science.gov (United States)

    Yeh, Chia-Hsien; Hsu, Yih-Chih

    2015-03-01

    The epidermal growth factor receptor (EGFR) over-regulation related to uncontrolled cell division and promotes progression in tumor. Over-expression of human epidermal growth factor receptor (EGFR) has been detected in oral cancer cells. EGFR-targeting agents are potential therapeutic modalities for treating oral cancer based on our in vitro study. Liposome nanotechnology is used to encapsulate siRNA and were modified with target ligand to receptors on the surface of tumor cells. We used EGFR siRNA to treat oral cancer in vitro.

  3. Lactic acid bacteria as antigen delivery vehicles for oral immunization purposes

    NARCIS (Netherlands)

    Pouwels, P.H.; Leer, R.J.; Shaw, M.; Heijne Den Bak-Glashouwer, M.J.; Tielen, F.D.; Smit, E.; Martinez, B.; Jore, J.; Conway, P.L.

    1998-01-01

    In vaccination programmes in which large numbers of subjects are involved, the oral route of administration is more convenient as compared to the more frequently used parenteral route. This is particularly relevant when vaccines are to be applied in less industrialized countries. Lactic acid

  4. Production of carcinogenic acetaldehyde by Candida albicans from patients with potentially malignant oral mucosal disorders.

    Science.gov (United States)

    Gainza-Cirauqui, M L; Nieminen, M T; Novak Frazer, L; Aguirre-Urizar, J M; Moragues, M D; Rautemaa, R

    2013-03-01

    Production of carcinogenic acetaldehyde by Candida has been suggested to contribute to epithelial dysplasia and oral carcinogenesis. Oral lichen planus (OLP), oral lichenoid lesion (OLL) and oral leukoplakia (OL) are potentially carcinogenic oral diseases where colonisation by Candida is common, but acetaldehyde production by Candida has not been studied. Acetaldehyde production in ethanol (11 mM), glucose (100 mM), ethanol-glucose (11 mM and 100 mM) or red wine (1200 mM ethanol) incubation by Candida albicans from patients with OLL (n = 6), OLP (n = 16), OL (n = 6) and controls (n = 6) was measured by gas chromatography. Participants completed a questionnaire regarding their smoking habits and alcohol consumption. All Candida albicans isolates produced potentially carcinogenic levels of acetaldehyde (>100 μM) in all incubations containing ethanol. The control group isolates produced the highest acetaldehyde levels. Isolates from smokers produced more acetaldehyde in all incubations than those from non-smokers. The difference was significant in ethanol-glucose incubation. Isolates from patients who were both smokers and drinkers produced the highest amounts when incubated in ethanol, ethanol-glucose and wine. Candida albicans isolated from potentially carcinogenic oral diseases can produce mutagenic amounts of acetaldehyde. Cigarette smoking and alcohol consumption may favour adaptational changes resulting in the upregulation of candidal acetaldehyde metabolism. © 2012 John Wiley & Sons A/S. All rights reserved.

  5. The role of hypoxia in oral cancer and potentially malignant disorders: a review.

    Science.gov (United States)

    Kujan, Omar; Shearston, Kate; Farah, Camile S

    2017-04-01

    Oral and oropharyngeal cancer are major health problems globally with over 500 000 new cases diagnosed annually. Despite the fact that oral cancer is a preventable disease and has the potential for early detection, the overall survival rate remains at around 50%. Most oral cancer cases are preceded by a group of clinical lesions designated 'potentially malignant disorders'. It is difficult to predict if and when these lesions may transform to malignancy, and in turn it is difficult to agree on appropriate management strategies. Understanding underlying molecular pathways would help in predicting the malignant transformation of oral potentially malignant disorders and ultimately identifying effective methods for early detection and prevention of oral cancer. Reprogramming energy metabolism is an emerging hallmark of cancer that is predominantly controlled by hypoxia-induced genes regulating angiogenesis, tumour vascularization, invasion, drug resistance and metastasis. This review aims to highlight the role of hypoxia in oral carcinogenesis and to suggest future research implications in this arena. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Permeation enhancing polymers in oral delivery of hydrophilic macromolecules: thiomer/GSH systems.

    Science.gov (United States)

    Bernkop-Schnürch, A; Kast, C E; Guggi, D

    2003-12-05

    Thiolated polymers (= thiomers) in combination with reduced glutathione (GSH) were shown to improve the uptake of hydrophilic macromolecules from the GI tract. The mechanism responsible for this permeation enhancing effect seems to be based on the thiol groups of the polymer. These groups inhibit protein tyrosine phosphatase, being involved in the closing process of tight junctions, via a GSH-mediated mechanism. The strong permeation enhancing effect of various thiomer/GSH systems such as poly(acrylic acid)-cysteine/GSH or chitosan-4-thio-butylamidine (chitosan-TBA)/GSH could be shown via permeation studies on freshly excised intestinal mucosa in Ussing-type chambers. Furthermore, the efficacy of the system was also shown in vivo. By utilizing poly(acrylic acid)-cysteine/GSH as carrier matrix, an absolute oral bioavailability for low molecular weight heparin of 19.9 +/- 9.3% and a pharmacological efficacy--calculated on the basis of the areas under the reduction in serum glucose levels of the oral formulation versus subcutaneous (s.c.) injection-for orally given insulin of 7% could be achieved. The incorporation of salmon calcitonin in chitosan-TBA/GSH led on the other hand to a pharmacological efficacy based on the areas under the reduction in plasma calcium levels of the oral thiomer formulation versus intravenous (i.v.) injection of 1.3%. Because of this high efficacy (i), the possibility to combine thiomer/GSH systems with additional low molecular weight permeation enhancers acting in other ways (ii) and minimal toxicological risks as these polymers are not absorbed from the GI tract (iii), thiolated polymers represent a promising novel tool for the oral administration of hydrophilic macromolecules.

  7. pH-sensitive thiolated nanoparticles facilitate the oral delivery of insulin in vitro and in vivo

    Science.gov (United States)

    Zhang, Yan; Lin, Xia; Du, Xuli; Geng, Sicong; Li, Hongren; Sun, Hong; Tang, Xing; Xiao, Wei

    2015-02-01

    In this work, we designed and developed a delivery system composed of enteric Eudragit L100-cysteine/reduced glutathione nanoparticles (Eul-cys/GSH NPs) for oral delivery of insulin. First, interactions between Eul-cys and mucin glycoproteins, which are believed to be the result of disulfide bonds, were confirmed using rheology experiments. Subsequently, the insulin-loaded Eul-cys/GSH NPs were prepared by the diffusion method using the rich gel network multipore structure at the surface of the Eul-cys when the pH was higher than the p Ka of Eul-cys polymer. The Eul-cys/GSH NPs obtained were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. The results obtained showed that the average particle size ranged from 240 to 280 nm, and the particles were almost spherical in shape. The in vitro drug release results showed that the Eul-cys/GSH NPs retained a large amount of insulin in simulated gastric fluid, while a significant insulin release was found in simulated intestinal fluid. The in situ release study suggested that NPs released a greater amount of FITC-insulin (49.2 %) into the intestinal mucus layer compared with that of FITC-insulin solution (16.4 %), which facilitating insulin delivery through the intestinal mucosa. Eul-cys/GSH NPs exhibited promising mucoadhesive properties demonstrated using an in vitro cell model. Consequently, NPs were introduced into the ileum loop of healthy rats, thus enhancing the intestinal absorption of insulin and providing a prolonged reduction in blood glucose levels. These results suggest that Eul-cys/GSH NPs may be a promising delivery system for the treatment of diabetes.

  8. pH-sensitive thiolated nanoparticles facilitate the oral delivery of insulin in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yan [Shenyang University, Normal College (China); Lin, Xia; Du, Xuli; Geng, Sicong [Shenyang Pharmaceutical University, Department of Pharmaceutics (China); Li, Hongren; Sun, Hong [Shenyang University, Normal College (China); Tang, Xing, E-mail: tanglab@126.com [Shenyang Pharmaceutical University, Department of Pharmaceutics (China); Xiao, Wei, E-mail: wzhzh-nj@tom.com [Jiangsu Kanion Pharmaceutical Co., Ltd (China)

    2015-02-15

    In this work, we designed and developed a delivery system composed of enteric Eudragit L100-cysteine/reduced glutathione nanoparticles (Eul-cys/GSH NPs) for oral delivery of insulin. First, interactions between Eul-cys and mucin glycoproteins, which are believed to be the result of disulfide bonds, were confirmed using rheology experiments. Subsequently, the insulin-loaded Eul-cys/GSH NPs were prepared by the diffusion method using the rich gel network multipore structure at the surface of the Eul-cys when the pH was higher than the pKa of Eul-cys polymer. The Eul-cys/GSH NPs obtained were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. The results obtained showed that the average particle size ranged from 240 to 280 nm, and the particles were almost spherical in shape. The in vitro drug release results showed that the Eul-cys/GSH NPs retained a large amount of insulin in simulated gastric fluid, while a significant insulin release was found in simulated intestinal fluid. The in situ release study suggested that NPs released a greater amount of FITC-insulin (49.2 %) into the intestinal mucus layer compared with that of FITC-insulin solution (16.4 %), which facilitating insulin delivery through the intestinal mucosa. Eul-cys/GSH NPs exhibited promising mucoadhesive properties demonstrated using an in vitro cell model. Consequently, NPs were introduced into the ileum loop of healthy rats, thus enhancing the intestinal absorption of insulin and providing a prolonged reduction in blood glucose levels. These results suggest that Eul-cys/GSH NPs may be a promising delivery system for the treatment of diabetes.

  9. pH-sensitive thiolated nanoparticles facilitate the oral delivery of insulin in vitro and in vivo

    International Nuclear Information System (INIS)

    Zhang, Yan; Lin, Xia; Du, Xuli; Geng, Sicong; Li, Hongren; Sun, Hong; Tang, Xing; Xiao, Wei

    2015-01-01

    In this work, we designed and developed a delivery system composed of enteric Eudragit L100-cysteine/reduced glutathione nanoparticles (Eul-cys/GSH NPs) for oral delivery of insulin. First, interactions between Eul-cys and mucin glycoproteins, which are believed to be the result of disulfide bonds, were confirmed using rheology experiments. Subsequently, the insulin-loaded Eul-cys/GSH NPs were prepared by the diffusion method using the rich gel network multipore structure at the surface of the Eul-cys when the pH was higher than the pKa of Eul-cys polymer. The Eul-cys/GSH NPs obtained were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. The results obtained showed that the average particle size ranged from 240 to 280 nm, and the particles were almost spherical in shape. The in vitro drug release results showed that the Eul-cys/GSH NPs retained a large amount of insulin in simulated gastric fluid, while a significant insulin release was found in simulated intestinal fluid. The in situ release study suggested that NPs released a greater amount of FITC-insulin (49.2 %) into the intestinal mucus layer compared with that of FITC-insulin solution (16.4 %), which facilitating insulin delivery through the intestinal mucosa. Eul-cys/GSH NPs exhibited promising mucoadhesive properties demonstrated using an in vitro cell model. Consequently, NPs were introduced into the ileum loop of healthy rats, thus enhancing the intestinal absorption of insulin and providing a prolonged reduction in blood glucose levels. These results suggest that Eul-cys/GSH NPs may be a promising delivery system for the treatment of diabetes

  10. Radiolabelling of potential colonic delivery systems by neutron activation. An evaluation based on physiochemical properties of excipients and formulations

    Energy Technology Data Exchange (ETDEWEB)

    Ahrabi, Sayeh

    1999-07-01

    The effects of neutron irradiation on the physicochemical properties of some potential release-controlling excipients for oral delivery to colon (based on microbially degradable polysaccharide or a combination of pH- and time-dependent mechanisms) were initially investigated. The aim was to choose the most irradiation-resistant ones for the development of a colonic delivery system to be radiolabelled by the neutron activation procedure. However, no correlation between the extent of irradiation-induced changes of the release-controlling polymers and the in vitro properties of the final formulation was observed. Incorporation of samarium oxide (Sm{sub 2}O{sub 3}) resulted in retardation of the drug release through the diffusion layer. The influence of neutron activation factors on the properties of some suppository combinations was also studied. The effect of the admixture of Sm{sub 2}O{sub 3} on the dissolution and disintegration of the suppositories was more profound than the effect of neutron irradiation. In hydrophilic suppositories, the effect of Sm{sub 2}O{sub 3} was dependent on the type, amount and the physicochemical characteristics of the incorporated drug. In lipophilic suppositories, the release-controlling effect of Sm{sub 2}O{sub 3} was hypothesised to be due to its insoluble micronised particles blocking the drug diffusion layer. The neutron activation procedure could be utilised for radiolabelling potential oral and rectal colonic drug delivery systems. However, to avoid alteration in the crucial in vitro characteristics of the formulations, the amount, the particle size and the aggregated particle characteristics of the lanthanide salt (e.g. Sm{sub 2}O{sub 3} or samarium stearate) together with the neutron irradiation dose should be controlled precisely for each dosage system. For the systems investigated in this work the release-controlling mechanism of the dosage form seems to be a key parameter to predict the extent of the influence of neutron

  11. Effect of Zeta Potential on the Properties of Nano-Drug Delivery ...

    African Journals Online (AJOL)

    The zeta potential (ZP) of colloidal systems and nano-medicines, as well as their particle size exert a major effect on the various properties of nano-drug delivery systems. Not only the stability of dosage forms and their release rate are affected but also their circulation in the blood stream and absorption into body membranes ...

  12. Investigation of Genipin Cross-Linked Microcapsule for Oral Delivery of Live Bacterial Cells and Other Biotherapeutics: Preparation and In Vitro Analysis in Simulated Human Gastrointestinal Model

    Directory of Open Access Journals (Sweden)

    Hongmei Chen

    2010-01-01

    Full Text Available Oral therapy utilizing engineered microorganisms has shown promise in the treatment of many diseases. By microencapsulation, viable cells can overcome the harsh gastrointestinal (GI environment and secrete needed therapeutics into the gut. These engineered cells should be encased without escaping into the GI tract for safety concerns, thus robust microcapsule membrane is requisite. This paper examined the GI performance of a novel microcapsule membrane using a dynamic simulated human GI model. Results showed that the genipin cross-linked alginate-chitosan (GCAC microcapsules possessed strong resistance to structural disintegration in the simulated GI environment. Leakage of encapsulated high molecular weight dextran, a model material to be protected during the simulated GI transit, was negligible over 72 h of exposure, in contrast to considerable leakage of dextran from the non-cross-linked counterparts. These microcapsules did not alter the microflora and enzymatic activities in the simulated human colonic media. This study suggested the potential of the GCAC microcapsules for oral delivery of live microorganisms and other biotherapeutics.

  13. Topical delivery of low-cost protein drug candidates made in chloroplasts for biofilm disruption and uptake by oral epithelial cells.

    Science.gov (United States)

    Liu, Yuan; Kamesh, Aditya C; Xiao, Yuhong; Sun, Victor; Hayes, Michael; Daniell, Henry; Koo, Hyun

    2016-10-01

    Protein drugs (PD) are minimally utilized in dental medicine due to high cost and invasive surgical delivery. There is limited clinical advancement in disrupting virulent oral biofilms, despite their high prevalence in causing dental caries. Poor efficacy of antimicrobials following topical treatments or to penetrate and disrupt formed biofilms is a major challenge. We report an exciting low-cost approach using plant-made antimicrobial peptides (PMAMPs) retrocyclin or protegrin with complex secondary structures (cyclic/hairpin) for topical use to control biofilms. The PMAMPs rapidly killed the pathogen Streptococcus mutans and impaired biofilm formation following a single topical application of tooth-mimetic surface. Furthermore, we developed a synergistic approach using PMAMPs combined with matrix-degrading enzymes to facilitate their access into biofilms and kill the embedded bacteria. In addition, we identified a novel role for PMAMPs in delivering drugs to periodontal and gingival cells, 13-48 folds more efficiently than any other tested cell penetrating peptides. Therefore, PDs fused with protegrin expressed in plant cells could potentially play a dual role in delivering therapeutic proteins to gum tissues while killing pathogenic bacteria when delivered as topical oral formulations or in chewing gums. Recent FDA approval of plant-produced PDs augurs well for clinical advancement of this novel concept. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Lipid nanocarriers (GeluPearl) containing amphiphilic lipid Gelucire 50/13 as a novel stabilizer: fabrication, characterization and evaluation for oral drug delivery

    International Nuclear Information System (INIS)

    Date, Abhijit A; Nagarsenker, Mangal S; Vador, Nimish; Jagtap, Aarti

    2011-01-01

    Purpose. To evaluate the ability of Gelucire 50/13 (an amphiphilic lipid excipient) to act as a stabilizer for lipid nanocarriers such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and to establish the ability of Gelucire 50/13 based lipid nanocarriers to improve oral delivery of hydrophobic drugs using repaglinide (RPG) as a model drug. Methods. The ability of Gelucire 50/13 to nanosize various solid lipids was evaluated. The ability of Gelucire 50/13 to yield NLC was evaluated by using Precirol ATO 5 as a model solid lipid and various liquid lipids (oils). Gelucire 50/13 based NLC (GeluPearl) were evaluated for their ability to improve the efficacy of RPG on oral administration in comparison to RPG tablets. The short term stability of RPG-GeluPearl was evaluated at 25 deg. C/60% RH. Results. Gelucire 50/13 could successfully yield SLN and NLC of various solid lipids, demonstrating its potential to act as a novel stabilizer. DSC studies indicated that Gelucire 50/13 interacts with Precirol ATO 5 and this interaction suppresses polymorphic transitions of both the components. RPG-GeluPearl exhibited significantly higher anti-diabetic activity compared to marketed RPG tablets. RPG-GeluPearl demonstrated good colloidal and chemical stability at the end of 1 month.

  15. Pokemon proto-oncogene in oral cancer: potential role in the early phase of tumorigenesis.

    Science.gov (United States)

    Sartini, D; Lo Muzio, L; Morganti, S; Pozzi, V; Di Ruscio, G; Rocchetti, R; Rubini, C; Santarelli, A; Emanuelli, M

    2015-05-01

    Oral squamous cell carcinoma (OSCC) represents about 90% of all oral neoplasms with a poor clinical prognosis. To improve survival of OSCC patients, it is fundamental to understand the basic molecular mechanisms characterizing oral carcinogenesis. Dysregulation of oncogenes and tumor suppressor genes seems to play a central role in tumorigenesis, including malignant transformation of the oral cavity. We analyzed the expression levels of the pro-oncogenic transcription factor Pokemon through real-time PCR, Western blot and immunohistochemistry in tumor, and normal oral tissue samples obtained from 22 patients with OSCC. The relationship between tumor characteristics and the level of Pokemon intratumor expression was also analyzed. Pokemon was significantly downregulated in OSCC. In particular, both mRNA and protein levels (tumor vs normal tissue) inversely correlated with histological grading, suggesting its potential role as a prognostic factor for OSCC. Moreover, a significant inverse correlation was found between Pokemon protein expression levels (OSCC vs normal oral mucosa) and tumor size, supporting the hypothesis that Pokemon could play an important role in the early phase of tumor expansion. This work shows that reduced expression of Pokemon is a peculiar feature of OSCC. Additional studies may establish the effective role of Pokemon in oral tumorigenesis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Cotransporting Ion is a Trigger for Cellular Endocytosis of Transporter-Targeting Nanoparticles: A Case Study of High-Efficiency SLC22A5 (OCTN2)-Mediated Carnitine-Conjugated Nanoparticles for Oral Delivery of Therapeutic Drugs.

    Science.gov (United States)

    Kou, Longfa; Yao, Qing; Sun, Mengchi; Wu, Chunnuan; Wang, Jia; Luo, Qiuhua; Wang, Gang; Du, Yuqian; Fu, Qiang; Wang, Jian; He, Zhonggui; Ganapathy, Vadivel; Sun, Jin

    2017-09-01

    OCTN2 (SLC22A5) is a Na + -coupled absorption transporter for l-carnitine in small intestine. This study tests the potential of this transporter for oral delivery of therapeutic drugs encapsulated in l-carnitine-conjugated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (LC-PLGA NPs) and discloses the molecular mechanism for cellular endocytosis of transporter-targeting nanoparticles. Conjugation of l-carnitine to a surface of PLGA-NPs enhances the cellular uptake and intestinal absorption of encapsulated drug. In both cases, the uptake process is dependent on cotransporting ion Na + . Computational OCTN2 docking analysis shows that the presence of Na + is important for the formation of the energetically stable intermediate complex of transporter-Na + -LC-PLGA NPs, which is also the first step in cellular endocytosis of nanoparticles. The transporter-mediated intestinal absorption of LC-PLGA NPs occurs via endocytosis/transcytosis rather than via the traditional transmembrane transport. The portal blood versus the lymphatic route is evaluated by the plasma appearance of the drug in the control and lymph duct-ligated rats. Absorption via the lymphatic system is the predominant route in the oral delivery of the NPs. In summary, LC-PLGA NPs can effectively target OCTN2 on the enterocytes for enhancing oral delivery of drugs and the critical role of cotransporting ions should be noticed in designing transporter-targeting nanoparticles. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. The potential of protein-nanomaterial interaction for advanced drug delivery

    DEFF Research Database (Denmark)

    Peng, Qiang; Mu, Huiling

    2016-01-01

    Nanomaterials, like nanoparticles, micelles, nano-sheets, nanotubes and quantum dots, have great potentials in biomedical fields. However, their delivery is highly limited by the formation of protein corona upon interaction with endogenous proteins. This new identity, instead of nanomaterial itself...... of such interaction for advanced drug delivery are presented........ Therefore, protein-nanomaterial interaction is a great challenge for nanomaterial systems and should be inhibited. However, this interaction can also be used to functionalize nanomaterials by forming a selected protein corona. Unlike other decoration using exogenous molecules, nanomaterials functionalized...

  18. FAST DISSOLVING THIN STRIPS: AN EMERGING WAY FOR ORAL DRUG DELIVERY

    OpenAIRE

    Anjali Joshi* and Ganesh Kumar

    2018-01-01

    Various pharmaceutical dosage form are present in the market but all of the dosage forms possess some drawback most common is patient incompliance which is seen in all age groups. So from last few years focus is done on developing such dosage form which enhances safety, efficacy and patient compliance. In this manner, in late 1970 fast-dissolving drug delivery system came in existence which includes Fast dissolving tablets and fast dissolving thin strips means those dosage form which dissolve...

  19. Photopatternable Magnetic Hollowbots by Nd-Fe-B Nanocomposite for Potential Targeted Drug Delivery Applications

    Directory of Open Access Journals (Sweden)

    Hui Li

    2018-04-01

    Full Text Available In contrast to traditional drug administration, targeted drug delivery can prolong, localize, target and have a protected drug interaction with the diseased tissue. Drug delivery carriers, such as polymeric micelles, liposomes, dendrimers, nanotubes, and so on, are hard to scale-up, costly, and have short shelf life. Here we show the novel fabrication and characterization of photopatternable magnetic hollow microrobots that can potentially be utilized in microfluidics and drug delivery applications. These magnetic hollowbots can be fabricated using standard ultraviolet (UV lithography with low cost and easily accessible equipment, which results in them being easy to scale up, and inexpensive to fabricate. Contact-free actuation of freestanding magnetic hollowbots were demonstrated by using an applied 900 G external magnetic field to achieve the movement control in an aqueous environment. According to the movement clip, the average speed of the magnetic hollowbots was estimated to be 1.9 mm/s.

  20. Evaluation of oral and subcutaneous delivery of an experimental canarypox recombinant canine distemper vaccine in the Siberian polecate (Mustela eversmanni)

    Science.gov (United States)

    Wimsatt, Jeffrey; Biggins, Dean E.; Innes, Kim; Taylor, Bobbi; Garell, Della

    2003-01-01

    the treatment groups. Survival rates were higher in animals with increasing serum neutralization titers (P = 0.027). This study demonstrates the efficacy of oral delivery of a recombinant CDV vaccine in the Siberian polecat. Further studies are needed to evaluate the safety and efficacy of vectored recombinant vaccines in highly susceptible species and especially in those species in which vaccination with modified live CDV has led to disease.

  1. Betel Quid and Oral Potentially Malignant Disorders in a Periurban Township in Myanmar.

    Science.gov (United States)

    Zaw, Ko-Ko; Ohnmar, Mya; Hlaing, Moh-Moh; Oo, Yin-Thet-Nu; Win, Swe-Swe; Htike, Maung-Maung-Than; Aye, Phyu-Phyu; Shwe, Sein; Htwe, Moe-Thida; Thein, Zaw-Moe

    2016-01-01

    This study aims to describe betel quid chewing practice and compare oral potentially malignant disorders between chewers and non-chewers of betel quid among residents in Dagon Myothit (East) Township, Myanmar. The study used a cross-sectional design conducted with a representative sample of 542 adults aged 18 years and above in the township. The trained interviewers collected data using a pretested structured questionnaire. On-site oral examination was done for suspected oral lesions. The mean age of the respondents was 45 years and 59% were women. Fifty-two percent of the respondents were currently in the habit of chewing betel quids (72% of men and 39% of women). Among 284 current betel quid chewers, 240 (85%) chewed betel quids together with tobacco. Out of 284 current betel quid chewers, 24 (8.5%) were found to have oral potentially malignant disorders; out of 258 betel quid non-chewers, only 1 (0.4%) was found to have oral potentially malignant disorders. This highlights the growing importance of smokeless tobacco use as public health problem.

  2. Oral keratinocyte stem/progenitor cells: specific markers, molecular signaling pathways and potential uses.

    Science.gov (United States)

    Calenic, Bogdan; Greabu, Maria; Caruntu, Constantin; Tanase, Cristiana; Battino, Maurizio

    2015-10-01

    Oral keratinocyte stem cells reside in the basal layers of the oral epithelium, representing a minor population of cells with a great potential to self-renew and proliferate over the course of their lifetime. As a result of the potential uses of oral keratinocyte stem cells in regenerative medicine and the key roles they play in tissue homeostasis, inflammatory conditions, wound healing and tumor initiation and progression, intense scientific efforts are currently being undertaken to identify, separate and reprogram these cells. Although currently there is no specific marker that can characterize and isolate oral keratinocyte stem cells, several suggestions have been made. Thus, different stem/progenitor-cell subpopulations have been categorized based on combinations of positive and/or negative membrane-surface markers, which include integrins, clusters of differentiation and cytokeratins. Important advances have also been made in understanding the molecular pathways that govern processes such as self-renewal, differentiation, proliferation, wound healing and programmed cell death. A thorough understanding of stem-cell biology and the molecular players that govern cellular fate is paramount in the quest for using stem-cell-derived therapies in the treatment of various oral pathologies. The current review focuses on recent advances in understanding the molecular signaling pathways coordinating the behavior of these cells and in identifying suitable markers used for their isolation and characterization. Special emphasis will also be placed on the roles played by oral keratinocyte stem and progenitor cells in normal and diseased oral tissues and on their potential uses in the fields of general medicine and dentistry. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. N-mercapto acetyl-N'-octyl-O, N″-glycol chitosan as an efficiency oral delivery system of paclitaxel.

    Science.gov (United States)

    Huo, Meirong; Fu, Ying; Liu, Yanhong; Chen, Qinyu; Mu, Yan; Zhou, Jianping; Li, Lingchao; Xu, Wei; Yin, Tingjie

    2018-02-01

    Herein, thioglycolic acid modified N-octyl-O, N'-glycol chitosan (N-mercapto acetyl-N'-octyl-O, N″-glycol chitosan, abbreviated as SH-OGC) was synthesized to improve the oral bioavailability of paclitaxel (PTX). PTX was readily solubilized into the hydrophobic inner core of SH-OGC. Pharmacokinetic studies demonstrated that the bioavailability of PTX was greatly enhanced when delivered by SH-OGC compared to Taxol ® or non-sulfhydrylated OGC micelles. Caco-2 cell experiments confirmed PTX or rhodamine-123-loaded SH-OGC demonstrated effective cellular accumulation via caveola-mediated endocytosis along with the inhibition of P-gp efflux. Furthermore, Caco-2 transport studies demonstrated that the mechanistic basis of SH-OGC efficacy was attributed to P-gp inhibition, enhanced permeability of tight junctions and clathrin-mediated transcytosis across the endothelium. In addition, SH-OGC exhibited increased intestinal retention through thiol-mediated mucoadhesion compared with OGC according to results of mucoadhesion evaluation on freshly excised rat intestine. In summary, SH-OGC micelles may present as a promising delivery vehicle for enhancing the oral bioavailability of P-gp substrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. In vivo evaluation of an oral delivery system for P-gp substrates based on thiolated chitosan.

    Science.gov (United States)

    Föger, Florian; Schmitz, Thierry; Bernkop-Schnürch, Andreas

    2006-08-01

    Recently, thiolated polymers, so called thiomers, have been reported to modulate drug absorption by inhibition of intestinal P-glycoprotein (P-gp). The aim of the present study was to provide a proof-of-principle for a delivery system based on thiolated chitosan in vivo in rats, using rhodamine-123 (Rho-123) as representative P-gp substrate. In vitro, the permeation enhancing effect of unmodified chitosan, chitosan-4 thiobutylamidine (Ch-TBA) and the combination of Ch-TBA with reduced glutathione (GSH) was evaluated by using freshly excised rat intestinal mucosa mounted in Ussing-type chambers. In comparison to buffer only, Rho-123 transport in presence of 0.5% (w/v) chitosan, 0.5% (w/v) Ch-TBA and the combination of 0.5% (w/v) Ch-TBA/0.5% (w/v) GSH, was 1.8-fold, 2.6-fold, 3.8-fold improved, respectively. Furthermore, enteric-coated tablets based on unmodified chitosan or Ch-TBA/GSH, were investigated in vivo. In rats, the Ch-TBA/GSH tablets increased the area under the plasma concentration time curve (AUC0-12) of Rho-123 by 217% in comparison to buffer control and by 58% in comparison to unmodified chitosan. This in vivo study showed that a delivery system based on thiolated chitosan significantly increased the oral bioavailability of P-gp substrate Rho-123.

  5. Polarity-sensitive nanocarrier for oral delivery of Sb(V and treatment of cutaneous leishmaniasis

    Directory of Open Access Journals (Sweden)

    Lanza JS

    2016-05-01

    Full Text Available Juliane S Lanza,1 Flaviana R Fernandes,1 José D Corrêa-Júnior,2 José MC Vilela,3 Rogério Magalhães-Paniago,4 Lucas AM Ferreira,5 Margareth S Andrade,3 Cynthia Demicheli,6 Maria N Melo,7 Frédéric Frézard1 1Department of Physiology and Biophysics, 2Department of Morphology, Instituto de Ciências Biológicas (ICB, Universidade Federal de Minas Gerais (UFMG, 3Innovation and Technology Center SENAI FIEMG – Campus CETEC, 4Department of Physics, Instituto de Ciências Exatas (ICEX, 5Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais (UFMG, 6Department of Chemistry, Instituto de Ciências Exatas (ICEX, 7Department of Parasitology, Instituto de Ciências Biológicas (ICB, Universidade Federal de Minas Gerais (UFMG, Belo Horizonte, Brazil Abstract: There is a great need for orally active drugs for the treatment of the neglected tropical disease leishmaniasis. Amphiphilic Sb(V complexes, such as 1:3 Sb–N-octanoyl-N-methylglucamide complex (SbL8, are promising drug candidates. It has been previously reported that SbL8 forms kinetically stabilized nanoassemblies in water and that this simple dispersion exhibits antileishmanial activity when given by oral route to a murine model of visceral leishmaniasis. The main objective of the present work was to interfere in the structural organization of these nanoassemblies so as to investigate their influence on the oral bioavailability of Sb, and ultimately, optimize an oral formulation of SbL8 for the treatment of cutaneous leishmaniasis. The structural organization of SbL8 nanoassemblies was manipulated through addition of propylene glycol (PG to the aqueous dispersion of SbL8. The presence of 50% (v/v PG resulted in the loss of hydrophobic microenvironment, as evidenced by fluorescence probing. However, nanostructures were still present, as demonstrated by dynamic light scattering, small-angle X-ray scattering, and atomic force microscopy (AFM. A

  6. Functionalized PLA-PEG nanoparticles targeting intestinal transporter PepT1 for oral delivery of acyclovir.

    Science.gov (United States)

    Gourdon, Betty; Chemin, Caroline; Moreau, Amélie; Arnauld, Thomas; Baumy, Philippe; Cisternino, Salvatore; Péan, Jean-Manuel; Declèves, Xavier

    2017-08-30

    Targeting intestinal di- and tri-peptide transporter PepT1 with prodrugs is a successful strategy to improve oral drug bioavailability, as demonstrated with valacyclovir, a prodrug of acyclovir. The aim of this new drug delivery strategy is to over-concentrate a poorly absorbed drug on the intestinal membrane surface by targeting PepT1 with functionalized polymer nanoparticles. In the present study, poly(lactic acid)-poly(ethylene glycol)-ligand (PLA-PEG-ligand) nanoparticles were obtained by nanoprecipitation. A factorial experimental design allowed us to identify size-influent parameters and to obtain optimized ≈30nm nanoparticles. Valine, Glycylsarcosine, Valine-Glycine, and Tyrosine-Valine were chemically linked to PLA-PEG. In Caco-2 cell monolayer model, competition between functionalized nanoparticles and [ 3 H]Glycylsarcosine, a strong substrate of PepT1, reduced [ 3 H]Glycylsarcosine transport from 22 to 46%. Acyclovir was encapsulated with a drug load of ≈10% in valine-functionalized nanoparticles, resulting in a 2.7-fold increase in permeability as compared to the free drug. An in vivo pharmacokinetic study in mice compared oral absorption of acyclovir after administration of 25mg/kg of valacyclovir, free or encapsulated acyclovir in functionalized nanoparticles. Acyclovir encapsulation did not statistically modify AUC or C max , but increased t 1/2 and MRT 1.3-fold as compared to free acyclovir. This new strategy is promising for poorly absorbed drugs by oral administration. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Oral delivery of Acid Alpha Glucosidase epitopes expressed in plant chloroplasts suppresses antibody formation in treatment of Pompe mice.

    Science.gov (United States)

    Su, Jin; Sherman, Alexandra; Doerfler, Phillip A; Byrne, Barry J; Herzog, Roland W; Daniell, Henry

    2015-10-01

    Deficiency of acid alpha glucosidase (GAA) causes Pompe disease in which the patients systemically accumulate lysosomal glycogen in muscles and nervous systems, often resulting in infant mortality. Although enzyme replacement therapy (ERT) is effective in treating patients with Pompe disease, formation of antibodies against rhGAA complicates treatment. In this report, we investigated induction of tolerance by oral administration of GAA expressed in chloroplasts. Because full-length GAA could not be expressed, N-terminal 410-amino acids of GAA (as determined by T-cell epitope mapping) were fused with the transmucosal carrier CTB. Tobacco transplastomic lines expressing CTB-GAA were generated through site-specific integration of transgenes into the chloroplast genome. Homoplasmic lines were confirmed by Southern blot analysis. Despite low-level expression of CTB-GAA in chloroplasts, yellow or albino phenotype of transplastomic lines was observed due to binding of GAA to a chloroplast protein that has homology to mannose-6 phosphate receptor. Oral administration of the plant-made CTB-GAA fusion protein even at 330-fold lower dose (1.5 μg) significantly suppressed immunoglobulin formation against GAA in Pompe mice injected with 500 μg rhGAA per dose, with several-fold lower titre of GAA-specific IgG1 and IgG2a. Lyophilization increased CTB-GAA concentration by 30-fold (up to 190 μg per g of freeze-dried leaf material), facilitating long-term storage at room temperature and higher dosage in future investigations. This study provides the first evidence that oral delivery of plant cells is effective in reducing antibody responses in ERT for lysosomal storage disorders facilitating further advances in clinical investigations using plant cell culture system or in vitro propagation. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  8. Gelatin coated hybrid lipid nanoparticles for oral delivery of amphotericin B

    DEFF Research Database (Denmark)

    Jain, Sanyog; Valvi, Pankaj U; Swarnakar, Nitin K

    2012-01-01

    Amphotericin B (AmB) loaded polymer lipid hybrid nanoparticles (AmB-PLNs) comprised of lecithin (anionic lipid) and gelatin (Type A, cationic below its isoelectric point 7.0-9.0) were prepared by a two-step desolvation method to improve the oral bioavailability of AmB. The optimized AmB-PLNs were......) and fluorescent resonance energy transfer (FRET) analysis confirmed the orientation of the lecithin (located in the core) and gelatin (exterior coat) within the system. The developed formulation exhibited a sustained drug release profile with a release pattern best fitted to Higuchi kinetics. Experiments on Caco...

  9. Prevalence of oral potentially malignant disorders in workers of Udupi taluk

    Directory of Open Access Journals (Sweden)

    Yeturu Sravan Kumar

    2015-01-01

    Full Text Available Objective: The objective was to assess the prevalence and risk factors of oral potentially malignant disorders (PMD among industrial workers of Udupi taluk, Karnataka. Materials and Methods: The sample consisted of industrial workers aged >18 years from randomly selected industries in Udupi Taluk. A self-administered questionnaire was given to the participants to assess sociodemographic factors and abusive habits (Tobacco, Alcohol, and Betel quid followed by clinical oral examination by single trained and calibrated examiner. Results: A total of 396 completed all steps of the survey and were included for analysis. A total of 14, 11.4, and 14.4% were tobacco, alcohol, and betel quid users, respectively. A total of 8.6% (n = 34 have at least one PMD. A significantly higher number of participants with single (11.4% or combined habits (60.4% had oral lesions while none of the participants without habits reported any oral lesions (P = 0.001. Conclusion: Prevalence of abusive habits and oral premalignant lesions or conditions was substantial among the workers. The cause and effect relationship and dose-response were also shown to be significantly associated. Prevention and early diagnosis through workplace screening are the major cornerstones for the control of oral cancer.

  10. Development and in vivo evaluation of an oral insulin-PEG delivery system.

    Science.gov (United States)

    Calceti, P; Salmaso, S; Walker, G; Bernkop-Schnürch, A

    2004-07-01

    Insulin-monomethoxypoly(ethylene glycol) derivatives were obtained by preparation of mono- and di-terbutyl carbonate insulin derivatives, reaction of available protein amino groups with activated 750 Da PEG and, finally, amino group de-protection. This procedure allowed for obtaining high yield of insulin-1PEG and insulin-2PEG. In vivo studies carried out by subcutaneous injection into diabetic mice demonstrated that the two bioconjugates maintained the native biological activity. In vitro, PEGylation was found to enhance the hormone stability towards proteases. After 1 h incubation with elastase, native insulin, insulin-1PEG and insulin-2PEG undergo about 70, 30 and 10% degradation, respectively, while in the presence of pepsin protein degradation was 100, 70 and 50%, respectively. The attachment of low molecular weight PEG did not significantly (P >0.05) alter insulin permeation behavior across the intestinal mucosa. Insulin-1PEG was formulated into mucoadhesive tablets constituted by the thiolated polymer poly(acrylic acid)-cysteine. The therapeutic agent was sustained released from these tablets within 5 h. In vivo, by oral administration to diabetic mice, the glucose levels were found to decrease of about 40% since the third hour from administration and the biological activity was maintained up to 30 h. According to these results, the combination of PEGylated insulin with a thiolated polymer used as drug carrier matrix might be a promising strategy for oral insulin administration.

  11. Development and characterization of orally-disintegrating films for propolis delivery

    Directory of Open Access Journals (Sweden)

    Josiane Gonçalves Borges

    2013-02-01

    Full Text Available This study aimed at evaluating the effect of different concentrations of hydrolyzed collagen (HC on the properties of an orally disintegrating film containing propolis ethanol extract (PEE as an active component. The films were evaluated in terms of total phenols, mechanical properties, solubility, contact angle, disintegration time, and microstructure. The films were prepared by casting with 2 g of protein mass (gelatin and HC, 30 g of sorbitol/100 g of protein mass, and 100 g of PEE/100 g of protein mass. HC was incorporated at concentrations of 0, 10, 20, and 30 g/100 g of protein mass. It was found that increased concentrations of HC reduced tensile strength and increased elongation; however, all films showed plastic behavior. An increase in solubility at 25 ºC, a reduction in the contact angle, and disintegration time were also observed. Thus, higher concentrations of collagen led to more hydrophilic and more soluble polymeric matrices that showed shorter dissolution time, favoring the use of these materials as carriers for active compounds to be delivered in the oral cavity.

  12. Oral Delivery of Probiotics in Poultry Using pH-Sensitive Tablets.

    Science.gov (United States)

    Jiang, Tao; Li, Hui-Shan; Han, Geon Goo; Singh, Bijay; Kang, Sang-Kee; Bok, Jin-Duck; Kim, Dae-Duk; Hong, Zhong-Shan; Choi, Yun-Jaie; Cho, Chong-Su

    2017-04-28

    As alternatives to antibiotics in livestocks, probiotics have been used, although most of them in the form of liquid or semisolid formulations, which show low cell viability after oral administration. Therefore, suitable dry dosage forms should be developed for livestocks to protect probiotics against the low pH in the stomach such that the products have higher probiotics survivability. Here, in order to develop a dry dosage forms of probiotics for poultry, we used hydroxypropyl methylcellulose phthalate 55 (HPMCP 55) as a tablet-forming matrix to develop probiotics in a tablet form for poultry. Here, we made three different kinds of probiotics-loaded tablet under different compression forces and investigated their characteristics based on their survivability, morphology, disintegration time, and kinetics in simulated gastrointestinal fluid. The results indicated that the probiotics formulated in the tablets displayed higher survival rates in acidic gastric conditions than probiotics in solution. Rapid release of the probiotics from the tablets occurred in simulated intestinal fluid because of fast swelling of the tablets in neutral pH. As a matrix of tablet, HPMCP 55 provided good viability of probiotics after 6 months under refrigeration. Moreover, after oral administration of probiotics-loaded tablets to chicken, more viable probiotics were observed, than with solution type, through several digestive areas of chicken by the tablets.

  13. From regenerative dentistry to regenerative medicine: progress, challenges, and potential applications of oral stem cells

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    Xiao L

    2014-12-01

    Full Text Available Li Xiao,1 Masanori Nasu2 1Department of Pharmacology, 2Research Center, The Nippon Dental University, Tokyo, Japan Abstract: Adult mesenchymal stem cells (MSCs and epithelial stem cells play essential roles in tissue repair and self-healing. Oral MSCs and epithelial stem cells can be isolated from adult human oral tissues, for example, teeth, periodontal ligament, and gingiva. Cocultivated adult oral epithelial stem cells and MSCs could represent some developmental events, such as epithelial invagination and tubular structure formation, signifying their potentials for tissue regeneration. Oral epithelial stem cells have been used in regenerative medicine over 1 decade. They are able to form a stratified cell sheet under three-dimensional culture conditions. Both experimental and clinical data indicate that the cell sheets can not only safely and effectively reconstruct the damaged cornea in humans, but also repair esophageal ulcer in animal models. Oral MSCs include dental pulp stem cells (DPSCs, stem cells from exfoliated deciduous teeth (SHED, stem cells from apical papilla (SCAP, periodontal ligament stem cells (PDLSCs, and mesenchymal stem cells from gingiva (GMSCs. They are widely applied in both regenerative dentistry and medicine. DPSCs, SHED, and SCAP are able to form dentin–pulp complex when being transplanted into immunodeficient animals. They have been experimentally used for the regeneration of dental pulp, neuron, bone muscle and blood vessels in animal models and have shown promising results. PDLSCs and GMSCs are demonstrated to be ideal cell sources for repairing the damaged tissues of periodontal, muscle, and tendon. Despite the abovementioned applications of oral stem cells, only a few human clinical trials are now underway to use them for the treatment of certain diseases. Since clinical use is the end goal, their true regenerative power and safety need to be further examined.Keywords: oral mesenchymal stem cells, oral

  14. MCM-2 expression differentiates potentially malignant verrucous lesions from oral carcinomas.

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    Niranjan, Kochli Channappa; Sarathy, Niharika Abhay; Alrani, Devendra

    2018-03-13

    Mcm-2 is a biomarker belonging to Mcm family of proteins which has rarely been used in oral potentially malignant and malignant lesions of the verrucous type. The objective of this study is to assess the expression of Mcm-2 in Normal Oral Mucosa (NM), Verrucous Hyperplasia (VH), Verrucous Carcinoma (VC) and Oral Squamous Cell Carcinoma (OSCC) and compare it with the clinicopathological characteristics. A total of 70 formalin fixed paraffin embedded tissue samples (10 cases of Normal Mucosa NM- Group A, 10 cases of Verrucous Hyperplasia- VH without Dysplasia- Group B, 10 cases of Verrucous Hyperplasia- VH with Dysplasia- Group C, 20 cases of Verrucous Carcinoma VC-Group D, 20 cases of Oral Squamous Cell Carcinoma OSCC- Group E) were subjected to immunohistochemistry with Mcm-2 antibody. Statistical analysis was carried out with various tests like ANOVA, Tukey HSD, Chi-Square and Shapiro-Wilk test by using the SPSS software. There was a significant difference in Mcm-2 expression with quantitative analysis among all the groups (p Mcm-2 may be a sensitive proliferation marker in oral potentially malignant and malignant lesions which may be useful for differentiating between VH with/ without dysplasia, VC and OSCC. Copyright © 2018. Published by Elsevier Inc.

  15. It's Story Time!: Exploring the Potential of Multimodality in Oral Storytelling to Support Children's Vocabulary Learning

    Science.gov (United States)

    Lwin, Soe Marlar

    2016-01-01

    Although many studies have been done on the benefits of parent/teacher-child interactions during shared storybook reading or read'aloud sessions, very few have examined the potential of professional storytellers' oral discourse to support children's vocabulary learning. In those storytelling sessions conducted by professional storytellers, the…

  16. Oral Delivery of Curcumin Polymeric Nanoparticles Ameliorates CCl4-Induced Subacute Hepatotoxicity in Wistar Rats

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    Gregory Marslin

    2018-05-01

    Full Text Available Curcumin is the major bioactive compound of Curcuma longa, an important medicinal plant used in traditional herbal formulations since ancient times. In the present study, we report that curcumin nanoparticles (ηCur protects Wistar rats against carbon tetrachloride (CCl4-induced subacute hepatotoxicity. Nanoparticles of sizes less than 220 nm with spherical shape were prepared using PLGA and PVA respectively as polymer and stabilizer. Test animals were injected via intraperitoneal route with 1 mL/kg CCl4 (8% in olive oil twice a week over a period of 8 weeks to induce hepatotoxicity. On the days following the CCl4 injection, test animals were orally administered with either curcumin or its equivalent dose of ηCur. Behavioural observation, biochemical analysis of serum and histopathological examination of liver of the experimental animals indicated that ηCur offer significantly higher hepatoprotection compared to curcumin.

  17. Synthesis and characterization of pH-sensitive drinkable nanoparticles for oral delivery of ibuprofen

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    Agostini, Azzurra; Capasso Palmiero, Umberto; Barbieri, Sara D. A.; Lupi, Monica; Moscatelli, Davide

    2018-06-01

    Ibuprofen (IBU) is a widespread drug used to treat both acute and chronic disorders. It is generally taken orally but the free drug can induce the irritation of the gastric mucosa due to its acid nature. In literature, different approaches have been adopted to prevent the release in the stomach, such as physical entrapment with film-coated tablets and drug-conjugates. Nevertheless, these solutions have many disadvantages, including the fast release of the drug and the difficulty to swallow the tablet, especially for children who may vomit or refuse the tablet. For this reason, in this work, novel formulations are proposed that do not require the encapsulation of the drug into a solid form and, in turn, their assumption as a pill. IBU has been linked to different types of methacrylates via ester bond in order to produce pH-responsive macromolecular monomers. The novelty is related to the use of these drug-conjugates macromonomer for the production of nanoparticles (NPs) via emulsion polymerization (EP), using water as solvent. The final emulsion is able to load up to 30 mg ml‑1 of IBU, so less than 10 ml is required to be assumed to reach the minimum therapeutic dose of the drug (200 mg). Finally, the release of IBU from these novel drinkable formulations has been investigated in the gastric and intestinal simulated fluids to show the preferential release of IBU from the NPs in basic conditions. A comparison with an existing oral suspension has been performed to highlight the slower release in acid environment of these new formulations. Afterwards, the IBU loaded NPs were tested in vitro showing lower toxicity compared to the free drug.

  18. Novel potential for optimization of antitubercular therapy: Pulmonary delivery of rifampicin lipospheres

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    Charan Singh

    2015-12-01

    Full Text Available The aim of the present work is to develop rifampicin loaded phospholipid lipospheres containing sulfphobutyl ether β-cyclodextrin and Vitamin C for inhalation to test their potential for deep lung delivery. The findings of the solid state characterization revealed the amorphous nature of the lipospheres. These exhibited a better flowability, an aerodynamic diameter in the range of 1.76 to 3.99 µm. Moreover, the fine particle fraction and emitted dose was found in the range of 68.84–83.73% and 80–93%, respectively. Moreover, lipospheres exhibited enhanced/equivalent efficacy in vitro in H37Rv strain. Hence, the results show the potential of lipospheres for pulmonary delivery of rifampicin.

  19. Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer's disease.

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    Muntimadugu, Eameema; Dhommati, Raju; Jain, Anjali; Challa, Venu Gopala Swami; Shaheen, M; Khan, Wahid

    2016-09-20

    Poor brain penetration of tarenflurbil (TFB) was one of the major reasons for its failure in phase III clinical trials conducted on Alzheimer's patients. Thus there is a tremendous need of developing efficient delivery systems for TFB. This study was designed with the aim of improving drug delivery to brain through intranasally delivered nanocarriers. TFB was loaded into two different nanocarriers i.e., poly (lactide-co-glycolide) nanoparticles (TFB-NPs) and solid lipid nanoparticles (TFB-SLNs). Particle size of both the nanocarriers (targeting site. Pharmacokinetics suggested improved circulation behavior of nanoparticles and the absolute bioavailabilities followed this order: TFB-NPs (i.n.)>TFB-SLNs (i.n.)>TFB solution (i.n.)>TFB suspension (oral). Brain targeting efficiency was determined in terms of %drug targeting efficiency (%DTE) and drug transport percentage (DTP). The higher %DTE (287.24) and DTP (65.18) were observed for TFB-NPs followed by TFB-SLNs (%DTE: 183.15 and DTP: 45.41) among all other tested groups. These encouraging results proved that therapeutic concentrations of TFB could be transported directly to brain via olfactory pathway after intranasal administration of polymeric and lipidic nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. MALDI imaging reveals NCOA7 as a potential biomarker in oral squamous cell carcinoma arising from oral submucous fibrosis.

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    Xie, Xiaoyan; Jiang, Yuchen; Yuan, Yao; Wang, Peiqi; Li, Xinyi; Chen, Fangman; Sun, Chongkui; Zhao, Hang; Zeng, Xin; Jiang, Lu; Zhou, Yu; Dan, Hongxia; Feng, Mingye; Liu, Rui; Chen, Qianming

    2016-09-13

    Oral squamous cell carcinoma (OSCC) ranks among the most common cancer worldwide, and is associated with severe morbidity and high mortality. Oral submucous fibrosis (OSF), characterized by fibrosis of the mucosa of the upper digestive tract, is a pre-malignant lesion, but the molecular mechanisms underlying this malignant transformation remains to be elucidated. In this study, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic strategy was employed to profile the differentially expressed peptides/proteins between OSCC tissues and the corresponding adjacent non-cancerous OSF tissues. Sixty-five unique peptide peaks and nine proteins were identified with altered expression levels. Of them, expression of NCOA7 was found to be up-regulated in OSCC tissues by immunohistochemistry staining and western blotting, and correlated with a pan of clinicopathologic parameters, including lesion site, tumor differentiation status and lymph node metastasis. Further, we show that overexpression of NCOA7 promotes OSCC cell proliferation in either in vitro or in vivo models. Mechanistic study demonstrates that NCOA7 induces OSCC cell proliferation probably by activating aryl hydrocarbon receptor (AHR). The present study suggests that NCOA7 is a potential biomarker for early diagnosis of OSF malignant transformation, and leads to a better understanding of the molecular mechanisms responsible for OSCC development.

  1. Development of a lozenge for oral transmucosal delivery of trans-resveratrol in humans: proof of concept.

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    Otis L Blanchard

    Full Text Available Resveratrol provides multiple physiologic benefits which promote healthspan in various model species and clinical trials support continued exploration of resveratrol treatment in humans. However, there remains concern regarding low bioavailability and wide inter-individual differences in absorption and metabolism in humans, which suggests a great need to develop novel methods for resveratrol delivery. We hypothesized that oral transmucosal delivery, using a lozenge composed of a resveratrol-excipient matrix, would allow resveratrol to be absorbed rapidly into the bloodstream. We pursued proof of concept through two experiments. In the first experiment, the solubility of trans-resveratrol (tRES in water and 2.0 M solutions of dextrose, fructose, ribose, sucrose, and xylitol was determined using HPLC. Independent t-tests with a Bonferroni correction were used to compare the solubility of tRES in each of the solutions to that in water. tRES was significantly more soluble in the ribose solution (p = 0.0013 than in the other four solutions. Given the enhanced solubility of tRES in a ribose solution, a resveratrol-ribose matrix was developed into a lozenge suitable for human consumption. Lozenges were prepared, each containing 146±5.5 mg tRES per 2000 mg of lozenge mass. Two healthy human participants consumed one of the prepared lozenges following an overnight fast. Venipuncture was performed immediately before and 15, 30, 45, and 60 minutes following lozenge administration. Maximal plasma concentrations (Cmax for tRES alone (i.e., resveratrol metabolites not included were 325 and 332 ng⋅mL(-1 for the two participants at 15 minute post-administration for both individuals. These results suggest a resveratrol-ribose matrix lozenge can achieve greater Cmax and enter the bloodstream faster than previously reported dosage forms for gastrointestinal absorption. While this study is limited by small sample size and only one method of resveratrol

  2. Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

    Science.gov (United States)

    Etame, Arnold B.

    The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non

  3. Sodium dependent multivitamin transporter (SMVT): a potential target for drug delivery.

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    Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Mitra, Ashim K

    2012-06-01

    Sodium dependent multivitamin transporter (SMVT; product of the SLC5A6 gene) is an important transmembrane protein responsible for translocation of vitamins and other essential cofactors such as biotin, pantothenic acid and lipoic acid. Hydropathy plot (Kyte-Dolittle algorithm) revealed that human SMVT protein consists of 635 amino acids and 12 transmembrane domains with both amino and carboxyl termini oriented towards the cytoplasm. SMVT is expressed in various tissues such as placenta, intestine, brain, liver, lung, kidney, cornea, retina and heart. This transporter displays broad substrate specificity and excellent capacity for utilization in drug delivery. Drug absorption is often limited by the presence of physiological (epithelial tight junctions), biochemical (efflux transporters and enzymatic degradation) and chemical (size, lipophilicity, molecular weight, charge etc.) barriers. These barriers may cause many potential therapeutics to be dropped from the preliminary screening portfolio and subsequent entry into the market. Transporter targeted delivery has become a powerful approach to deliver drugs to target tissues because of the ability of the transporter to translocate the drug to intracellular organelles at a higher rate. This review highlights studies employing SMVT transporter as a target for drug delivery to improve bioavailability and investigate the feasibility of developing SMVT targeted drug delivery systems.

  4. Screening for oral potentially malignant disorders among areca (betel) nut chewers in Guam and Saipan.

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    Paulino, Yvette C; Hurwitz, Eric L; Warnakulasuriya, Saman; Gatewood, Robert R; Pierson, Kenneth D; Tenorio, Lynnette F; Novotny, Rachel; Palafox, Neal A; Wilkens, Lynne R; Badowski, Grazyna

    2014-12-11

    The Mariana Islands, including Guam and Saipan, are home to many ethnic subpopulations of Micronesia. Oral cancer incidence rates vary among subpopulations, and areca (betel) nut chewing, a habit with carcinogenic risks, is common. Our objectives were to conduct a screening program to detect oral potentially malignant disorders (OPMD) in betel nut chewers, measure their betel nut chewing practices, and assess the prevalence of the oral human papillomavirus (HPV) infection in a subset of betel nut chewers in these islands. A cross-section of 300 betel nut chewers ≥18 years old [in Guam (n = 137) and in Saipan (n = 163)] were recruited between January 2011-June 2012. We collected demographic, socioeconomic, and oral behavioural characteristics. Latent class analysis was used to identify chewing patterns from selected chewing behaviours. Following calibration of OPMD against an expert, a registered oral hygienist conducted oral examinations by house to house visits and referred positive cases to the study dentist for a second oral examination. Buccal smears were collected from a subset (n = 123) for HPV testing. Two classes of betel nut chewers were identified on 7 betel nut behaviours, smoking, and alcohol use; a key difference between the two Classes was the addition of ingredients to the betel quid among those in Class 2. When compared on other characteristics, Class 1 chewers were older, had been chewing for more years, and chewed fewer nuts per day although chewing episodes lasted longer than Class 2 chewers. More Class 1 chewers visited the dentist regularly than Class 2 chewers. Of the 300 participants, 46 (15.3%; 3.8% for Class 1 and 19.4% for Class 2) had OPMD and one (0.3%) was confirmed to have squamous cell carcinoma. The prevalence of oral HPV was 5.7% (7/123), although none were high-risk types. We found two patterns of betel nut chewing behaviour; Class 2 had a higher frequency of OPMD. Additional epidemiologic research is needed to

  5. Carcinogenesis of the Oral Cavity: Environmental Causes and Potential Prevention by Black Raspberry.

    Science.gov (United States)

    El-Bayoumy, Karam; Chen, Kun-Ming; Zhang, Shang-Min; Sun, Yuan-Wan; Amin, Shantu; Stoner, Gary; Guttenplan, Joseph B

    2017-01-17

    strain, cellular and molecular targets, and relative carcinogenic potency, our animal model may offer a more realistic platform to study oral carcinogenesis. In this perspective, we also discuss our preclinical studies to demonstrate the potential of black raspberry extracts on the prevention of OSCC. Specifically, we were the first to demonstrate that black raspberry inhibited DB[a,l]P-DNA binding and of particular importance its capacity to enhance the repair of DB[a,l]P-induced bulky lesions in DNA. We believe that the information presented in this perspective will stimulate further research on the impact of environmental carcinogens in the development of oral cancer and may lead to novel strategies toward the control and prevention of this disease.

  6. Oral squamous cell carcinoma proliferative phenotype is modulated by proanthocyanidins: a potential prevention and treatment alternative for oral cancer

    Directory of Open Access Journals (Sweden)

    Swapp Aaron

    2007-06-01

    Full Text Available Abstract Background Despite the recently reported drop in the overall death rate from cancer, the estimated survival rate and number of deaths from oral cancer remain virtually unchanged. Early detection efforts, in combination with strategies for prevention and risk-reduction, have the potential to dramatically improve clinical outcomes. The identification of non-toxic, effective treatments, including complementary and alternative therapies, is critical if the survival rate is to be improved. Epidemiologic studies have suggested a protective effect from certain plant-derived foods and extracts; however, it has been difficult to isolate and identify the compounds most responsible for these observations. The primary purpose of this study was to investigate the response of human oral squamous cell carcinoma (OSCC to proanthocyanidin (PAC, a plant-derived compound that may inhibit the progression of several other cancers. Methods Using a series of in vitro assays, we sought to quantify the effects of PAC on OSCC, cervical carcinoma, and non-cancerous cell lines, specifically the effects of PAC on cell proliferation. Recent data suggest that infection with the human papillomavirus (HPV may also modulate the proliferative potential of OSCC; therefore, we also measured the effects of PAC administration on HPV-transfected OSCC proliferation. Results Our results demonstrated that PAC administration was sufficient to significantly suppress cellular proliferation of OSCC in a dose-dependent manner. In addition, the increased proliferation of OSCC after transfection with HPV 16 was reduced by the administration of PAC, as was the proliferation of the cervical cancer and non-cancerous cell lines tested. Our results also provide preliminary evidence that PAC administration may induce apoptosis in cervical and oral cancer cell lines, while acting merely to suppress proliferation of the normal cell line control. Conclusion These results signify that PAC may be

  7. Lactoferrin bioconjugated solid lipid nanoparticles: a new drug delivery system for potential brain targeting.

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    Singh, Indu; Swami, Rajan; Pooja, Deep; Jeengar, Manish Kumar; Khan, Wahid; Sistla, Ramakrishna

    2016-01-01

    Delivery of drugs to brain is a subtle task in the therapy of many severe neurological disorders. Solid lipid nanoparticles (SLN) easily diffuse the blood-brain barrier (BBB) due to their lipophilic nature. Furthermore, ligand conjugation on SLN surface enhances the targeting efficiency. Lactoferin (Lf) conjugated SLN system is first time attempted for effective brain targeting in this study. Preparation of Lf-modified docetaxel (DTX)-loaded SLN for proficient delivery of DTX to brain. DTX-loaded SLN were prepared using emulsification and solvent evaporation method and conjugation of Lf on SLN surface (C-SLN) was attained through carbodiimide chemistry. These lipidic nanoparticles were evaluated by DLS, AFM, FTIR, XRD techniques and in vitro release studies. Colloidal stability study was performed in biologically simulated environment (normal saline and serum). These lipidic nanoparticles were further evaluated for its targeting mechanism for uptake in brain tumour cells and brain via receptor saturation studies and distribution studies in brain, respectively. Particle size of lipidic nanoparticles was found to be optimum. Surface morphology (zeta potential, AFM) and surface chemistry (FTIR) confirmed conjugation of Lf on SLN surface. Cytotoxicity studies revealed augmented apoptotic activity of C-SLN than SLN and DTX. Enhanced cytotoxicity was demonstrated by receptor saturation and uptake studies. Brain concentration of DTX was elevated significantly with C-SLN than marketed formulation. It is evident from the cytotoxicity, uptake that SLN has potential to deliver drug to brain than marketed formulation but conjugating Lf on SLN surface (C-SLN) further increased the targeting potential for brain tumour. Moreover, brain distribution studies corroborated the use of C-SLN as a viable vehicle to target drug to brain. Hence, C-SLN was demonstrated to be a promising DTX delivery system to brain as it possessed remarkable biocompatibility, stability and efficacy than

  8. Alendronate-Loaded Modified Drug Delivery Lipid Particles Intended for Improved Oral and Topical Administration

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    Lacramioara Ochiuz

    2016-06-01

    Full Text Available The present paper focuses on solid lipid particles (SLPs, described in the literature as the most effective lipid drug delivery systems that have been introduced in the last decades, as they actually combine the advantages of polymeric particles, hydrophilic/lipophilic emulsions and liposomes. In the current study, we present our most recent advances in the preparation of alendronate (AL-loaded SLPs prepared by hot homogenization and ultrasonication using various ratios of a self-emulsifying lipidic mixture of Compritol 888, Gelucire 44/14, and Cremophor A 25. The prepared AL-loaded SLPs were investigated for their physicochemical, morphological and structural characteristics by dynamic light scattering, differential scanning calorimetry, thermogravimetric and powder X-ray diffraction analysis, infrared spectroscopy, optical and scanning electron microscopy. Entrapment efficacy and actual drug content were assessed by a validated HPLC method. In vitro dissolution tests performed in simulated gastro-intestinal fluids and phosphate buffer solution pH 7.4 revealed a prolonged release of AL of 70 h. Additionally, release kinetics analysis showed that both in simulated gastrointestinal fluids and in phosphate buffer solution, AL is released from SLPs based on equal ratios of lipid excipients following zero-order kinetics, which characterizes prolonged-release drug systems.

  9. Enhanced oral bioavailability of valsartan using a polymer-based supersaturable self-microemulsifying drug delivery system

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    Yeom DW

    2017-05-01

    Full Text Available Dong Woo Yeom,1,* Bo Ram Chae,2,* Ho Yong Son,1 Jin Han Kim,1 Jun Soo Chae,1 Seh Hyon Song,2 Dongho Oh,2 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, 2Daewon Pharm. Co., Ltd, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: A novel, supersaturable self-microemulsifying drug delivery system (S-SMEDDS was successfully formulated to enhance the dissolution and oral absorption of valsartan (VST, a poorly water-soluble drug, while reducing the total quantity for administration. Poloxamer 407 is a selectable, supersaturating agent for VST-containing SMEDDS composed of 10% Capmul® MCM, 45% Tween® 20, and 45% Transcutol® P. The amounts of SMEDDS and Poloxamer 407 were chosen as formulation variables for a 3-level factorial design. Further optimization was established by weighting different levels of importance on response variables for dissolution and total quantity, resulting in an optimal S-SMEDDS in large quantity (S-SMEDDS_LQ; 352 mg in total and S-SMEDDS in reduced quantity (S-SMEDDS_RQ; 144.6 mg in total. Good agreement was observed between predicted and experimental values for response variables. Consequently, compared with VST powder or suspension and SMEDDS, both S-SMEDDS_LQ and S-SMEDDS_RQ showed excellent in vitro dissolution and in vivo oral bioavailability in rats. The magnitude of dissolution and absorption-enhancing capacities using quantity-based comparisons was in the order S-SMEDDS_RQ > S-SMEDDS_LQ > SMEDDS > VST powder or suspension. Thus, we concluded that, in terms of developing an effective SMEDDS preparation with minimal total quantity, S-SMEDDS_RQ is a promising candidate. Keywords: valsartan, SMEDDS, supersaturation, factorial design, optimization, bio­availability 

  10. Enhancement of oral bioavailability of E804 by self-nanoemulsifying drug delivery system (SNEDDS) in rats.

    Science.gov (United States)

    Heshmati, Nasim; Cheng, Xinlai; Eisenbrand, Gerhard; Fricker, Gert

    2013-10-01

    Indirubin and its derivatives have been shown to interrupt the cell cycle by inhibiting cyclin-dependent kinases, explaining their long-time use in traditional Chinese medicine for the treatment of chronic myelocytic leukemia. A potent derivative of indirubin, indirubin-3'-oxime 2,3-dihydroxypropyl ether (E804), has been shown to block the Src-Stat3 and Src-Stat5 signaling pathway in human cancer cells, inducing apoptosis. The anticancer effects of E804, however, cannot be easily examined in vivo because of its poor water solubility and low absorption. The aim of this study was to develop and evaluate a self-nanoemulsifying drug delivery system (SNEDDS) containing E804 for enhancing its solubility and bioavailability. Solubility of E804 was determined in various vehicles, and pseudoternary phase diagram was used to evaluate the self-emulsifying existence area. The SNEDDS composed of Capmul MCM (oil), Solutol HS 15 (surfactant), and polyethylene glycol 400 (cosurfactant) on the ratio of 20.5:62.5:16 loaded 1.5% of E804. The particle size of droplets was found to be 16.8 and 140 nm, and SNEDDS was stable after freeze-thaw cycles and upon dilution in HCl 0.1 N and pH 7.4 HBSS++. The ability of formulation for absorption enhancement was studied in rats in vivo after oral administration. The results showed that the developed SNEDDS increased the E804 bioavailability 984.23% compared with the aqueous suspension. Our studies for the first time show that the developed SNEDDS can be used as a possible formulation for E804 to improve its solubility and oral bioavailability. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  11. Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruzi▿

    Science.gov (United States)

    Cazorla, Silvia I.; Becker, Pablo D.; Frank, Fernanda M.; Ebensen, Thomas; Sartori, María J.; Corral, Ricardo S.; Malchiodi, Emilio L.; Guzmán, Carlos A.

    2008-01-01

    To stimulate both local and systemic immune responses against Trypanosoma cruzi, Salmonella enterica serovar Typhimurium aroA was exploited as a DNA delivery system for cruzipain (SCz). In a murine model we compared SCz alone (GI) or coadministered with Salmonella carrying a plasmid encoding granulocyte-macrophage colony-stimulating factor (GII), as well as protocols in which SCz priming was followed by boosting with recombinant cruzipain (rCz) admixed with either CpG-ODN (GIII) or MALP-2, a synthetic derivative of a macrophage-activating lipopeptide of 2 kDa from Mycoplasma fermentans (GIV). The results showed that protocols that included four oral doses of SCz (GI) elicited mainly a mucosal response characterized by immunoglobulin A (IgA) secretion and proliferation of gut-associated lymphoid tissue cells, with weak systemic responses. In contrast, the protocol that included a boost with rCz plus CpG (GIII) triggered stronger systemic responses in terms of Cz-specific serum IgG titers, splenocyte proliferation, gamma interferon (IFN-γ) secretion, and delayed-type hypersensitivity response. Trypomastigote challenge of vaccinated mice resulted in significantly lower levels of parasitemia compared to controls. Protection was abolished by depletion of either CD4+ or CD8+ T cells. Parasite control was also evident from the reduction of tissue damage, as revealed by histopathologic studies and serum levels of enzymes that are markers of muscle injury in chronic Chagas' disease (i.e., creatine kinase, aspartate aminotransferase, and lactate dehydrogenase). Enhanced release of IFN-γ and interleukin-2 was observed in GI and GII upon restimulation of splenocytes in the nonparasitic phase of infection. Our results indicate that Salmonella-mediated delivery of Cz-DNA by itself promotes the elicitation of an immune response that controls T. cruzi infection, thereby reducing parasite loads and subsequent damage to muscle tissues. PMID:17967857

  12. Enteric-coated capsules filled with mono-disperse micro-particles containing PLGA-lipid-PEG nanoparticles for oral delivery of insulin.

    Science.gov (United States)

    Yu, Fei; Li, Yang; Liu, Chang Sheng; Chen, Qin; Wang, Gui Huan; Guo, Wei; Wu, Xue E; Li, Dong Hui; Wu, Winston Duo; Chen, Xiao Dong

    2015-04-30

    The success of the oral delivery of insulin (INS) as a therapeutic protein drug would significantly improve the quality of life of diabetic patients who would otherwise receive multiple daily INS injections. The oral delivery of INS, however, is still limited in its delivery efficiency, which could be due to the chemical, enzymatic, and adsorption barriers. In this work, in an attempt to improve the delivery efficiency, the INS-loaded polymer-lipid hybrid nanoparticles (INS-PLGA-lipid-PEG NPs) were designed and constructed through a double-emulsion solvent evaporation technique, followed by formulation of the spherical micro-particles using a spray freeze dryer (SFD). This kind of dryers has a uniquely designed microfluidic aerosol nozzle (MFAN), ensuring the formation of uniform particles. The resulted particles of ∼212 μm could easily be reverted to discrete INS-PLGA-lipid-PEG NPs in an aqueous solution. The INS-PLGA-lipid-PEG NPs created in this work showed a highly negative surface charge, excellent entrapment efficiency (92.3%) and a sustained drug release (∼24 h). Confocal laser scanning microscopy and flow cytometer were used to show that the cellular uptake efficiency for the INS-PLGA-lipid-PEG NPs was more effective than the INS in Caco-2 cells. More importantly, the in vivo pharmacodynamics demonstrated that the orally delivered system induced a prolonged decrease in blood glucose levels among diabetic rats. The relative bioavailability of INS compared with subcutaneous injection in diabetic rats was found to be approximately 12%. These results suggested that the encapsulated INS-PLGA-lipid-PEG NPs are promising and should be investigated further in the near future as an effective INS oral delivery system. Copyright © 2015. Published by Elsevier B.V.

  13. In vivo evaluation of anionic thiolated polymers as oral delivery systems for efflux pump inhibition.

    Science.gov (United States)

    Palmberger, Thomas F; Laffleur, Flavia; Greindl, Melanie; Bernkop-Schnürch, Andreas

    2015-08-01

    Recently, the cationic polymer thiolated chitosan has been reported to modulate drug absorption by inhibition of intestinal efflux pumps. The objective of this study was to evaluate in vitro and in vivo whether thiolated anionic biopolymers also show an efflux pump inhibitory effect in order to improve intestinal transcellular drug uptake. Therefore, three thiomers have been synthesized due covalent attachment of cysteine to various polymer backbones: pectin-cysteine (pect-cys), carboxymethylcellulose-cysteine (CMC-cys) and alginate-cysteine (alg-cys). In vitro, the permeation enhancing properties of these thiomers and their corresponding unmodified polymers have been evaluated on rat small intestine in Ussing-type chambers, using sulforhodamine 101 (SR-101) as MRP2 model substrate. In comparison to buffer only, SR-101 transport in presence of pect-cys, CMC-cys and alg-cys was improved 1.5-fold, 1.8-fold and 3.0-fold, respectively. Due to the comparatively best in vitro performance of thiolated alginate, it has been chosen for in vivo studies: a SR-101 solution containing 4% (w/v) alg-cys led to an AUC0 ≥ 12 of SR-101 of 109 ng ml(-1)h in rats representing a 3.8-fold improvement in comparison to a SR-101 buffer solution. Unmodified alginate improved the AUC0 ≥ 12 of SR-101 by a factor of 1.9. These findings suggest thiolated alginate as promising auxiliary agent for drugs being anionic efflux pump substrates, since the oral bioavailability of a MRP2 substrate could be significantly improved. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Oral transmucosal delivery of domperidone from immediate release films produced via hot-melt extrusion technology.

    Science.gov (United States)

    Palem, Chinna Reddy; Kumar Battu, Sunil; Maddineni, Sindhuri; Gannu, Ramesh; Repka, Michael A; Yamsani, Madhusudan Rao

    2013-02-01

    The objective of the study was to prepare and characterize the domperidone (DOM) hot-melt extruded (HME) buccal films by both in vitro and in vivo techniques. The HME film formulations contained PEO N10 and/or its combination with HPMC E5 LV or Eudragit RL100 as polymeric carriers, and PEG3350 as a plasticizer. The blends were co-processed at a screw speed of 50 rpm with the barrel temperatures ranging from 120-160°C utilizing a bench top co-rotating twin-screw hot-melt extruder using a transverse-slit die. The HME films were evaluated for drug content, drug excipient interaction, in vitro drug release, mechanical properties, in vivo residence time, in vitro bioadhesion, swelling and erosion, ex vivo permeation from HME films and the selected optimal formulation was subjected for bioavailability studies in healthy human volunteers. The extruded films demonstrated no drug excipient interaction and excellent content uniformity. The selected HME film formulation (DOM2) exhibited a tensile strength (0.72 Kg/mm(2)), elongation at break (28.4% mm(2)), in vivo residence time (120 min), peak detachment force (1.55 N), work of adhesion (1.49 mJ), swelling index (210.2%), erosion (10.5%) and in vitro drug release of 84.8% in 2 h. Bioavailability from the optimized HME buccal films was 1.5 times higher than the oral dosage form and the results showed statistically significant (p buccal-adhesive films with improved bioavailability characteristics.

  15. Controlled Systemic Delivery by Polymeric Implants Enhances Tissue and Plasma Curcumin Levels Compared with Oral Administration

    Science.gov (United States)

    Bansal, Shyam S.; Kausar, Hina; Vadhanam, Manicka V.; Ravoori, Srivani; Gupta, Ramesh C.

    2012-01-01

    Curcumin possess potent anti-inflammatory and anti-proliferative activities but with poor biopharmaceutical attributes. To overcome these limitations, curcumin implants were developed and tissue (plasma, brain and liver) curcumin concentrations were measured in female ACI rats for 3 months. Biological efficacy of tissue levels achieved was analyzed by modulation of hepatic cytochromes. Curcumin implants exhibited diffusion-mediated biphasic release pattern with ~2-fold higher in vivo release as compared to in vitro. Plasma curcumin concentration from implants was ~3.3 ng/ml on day 1 which dropped to ~0.2 ng/ml after 3 months whereas only 0.2–0.3 ng/ml concentration was observed from 4–12 days with diet and was undetected subsequently. Almost 10 fold higher curcumin levels were observed in brain on day 1 from implants compared with diet (30.1±7.3 vs 2.7±0.8 ng/g) and were higher even after 90 days (7.7±3.8 vs 2.2±0.8 ng/g). Although, curcumin levels were similar in liver from both the routes (~25–30 ng/g from day 1–4 and ~10–15 ng/g at 90 days), implants were more efficacious in altering hepatic CYP1A1 levels and CYP3A4 activity at ~28 fold lower doses. Curcumin implants provided much higher plasma and tissue concentrations and are a viable alternative for delivery of curcumin to various organs like brain. PMID:22227368

  16. Anticancer Activities of Surfactin and Potential Application of Nanotechnology Assisted Surfactin Delivery

    Directory of Open Access Journals (Sweden)

    Yuan-Seng Wu

    2017-10-01

    Full Text Available Surfactin, a cyclic lipopeptide biosurfactant produced by various strains of Bacillus genus, has been shown to induce cytotoxicity against many cancer types, such as Ehrlich ascites, breast and colon cancers, leukemia and hepatoma. Surfactin treatment can inhibit cancer progression by growth inhibition, cell cycle arrest, apoptosis, and metastasis arrest. Owing to the potent effect of surfactin on cancer cells, numerous studies have recently investigated the mechanisms that underlie its anticancer activity. The amphiphilic nature of surfactin allows its easy incorporation nano-formulations, such as polymeric nanoparticles, micelles, microemulsions, liposomes, to name a few. The use of nano-formulations offers the advantage of optimizing surfactin delivery for an improved anticancer therapy. This review focuses on the current knowledge of surfactin properties and biosynthesis; anticancer activity against different cancer models and the underlying mechanisms involved; as well as the potential application of nano-formulations for optimal surfactin delivery.

  17. Potential of surface-eroding poly(ethylene carbonate) for drug delivery to macrophages

    DEFF Research Database (Denmark)

    Bohr, Adam; Water, Jorrit J; Wang, Yingya

    2016-01-01

    Films composed of poly(ethylene carbonate) (PEC), a biodegradable polymer, were compared with poly(lactide-co-glycolide) (PLGA) films loaded with and without the tuberculosis drug rifampicin to study the characteristics and performance of PEC as a potential carrier for controlled drug delivery...... to macrophages. All drug-loaded PLGA and PEC films were amorphous indicating good miscibility of the drug in the polymers, even at high drug loading (up to 50wt.%). Polymer degradation studies showed that PLGA degraded slowly via bulk erosion while PEC degraded more rapidly and near-linearly via enzyme mediated...... surface erosion (by cholesterol esterase). Drug release studies performed with polymer films indicated a diffusion/erosion dependent delivery behavior for PLGA while an almost zero-order drug release profile was observed from PEC due to the controlled polymer degradation process. When exposed to polymer...

  18. In-flight food delivery and waste collection service: the passengers’ perspective and potential improvement

    Science.gov (United States)

    Romli, F. I.; Rahman, K. Abdul; Ishak, F. D.

    2016-10-01

    Increased competition in the commercial air transportation industry has made service quality of the airlines as one of the key competitive measures to attract passengers against their rivals. In-flight services, particularly food delivery and waste collection, have a notable impact on perception of the overall airline's service quality because they are directly and interactively provided to passengers during flight. An online public survey is conducted to explore general passengers' perception of current in-flight food delivery and waste collection services, and to identify potential rooms for improvement. The obtained survey results indicate that in-flight service does have an effect on passengers' choice of airlines. Several weaknesses of the current service method and possible improvements have been established from the collected responses.

  19. Oral Delivery of Probiotics Expressing Dendritic Cell-Targeting Peptide Fused with Porcine Epidemic Diarrhea Virus COE Antigen: A Promising Vaccine Strategy against PEDV.

    Science.gov (United States)

    Wang, Xiaona; Wang, Li; Huang, Xuewei; Ma, Sunting; Yu, Meiling; Shi, Wen; Qiao, Xinyuan; Tang, Lijie; Xu, Yigang; Li, Yijing

    2017-10-25

    Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, is the causative agent of porcine epidemic diarrhea (PED) that damages intestinal epithelial cells and results in severe diarrhea and dehydration in neonatal suckling pigs with up to 100% mortality. The oral vaccine route is reported as a promising approach for inducing protective immunity against PEDV invasion. Furthermore, dendritic cells (DCs), professional antigen-presenting cells, link humoral and cellular immune responses for homeostasis of the intestinal immune environment. In this study, in order to explore an efficient oral vaccine against PEDV infection, a mucosal DC-targeting oral vaccine was developed using Lactobacillus casei to deliver the DC-targeting peptide (DCpep) fused with the PEDV core neutralizing epitope (COE) antigen. This probiotic vaccine could efficiently elicit secretory immunoglobulin A (SIgA)-based mucosal and immunoglobulin G (IgG)-based humoral immune responses via oral vaccination in vivo. Significant differences ( p targeting peptide fused with PEDV COE antigen. This mucosal DC-targeting oral vaccine delivery effectively enhances vaccine antigen delivery efficiency, providing a useful strategy to induce efficient immune responses against PEDV infection.

  20. Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen

    DEFF Research Database (Denmark)

    Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    formulation in contrast to that of clinically available tamoxifen citrate when measured as function of hepatotoxicity markers and histopathological changes. CONCLUSIONS: In nutshell, co-encapsulation of quercetin with tamoxifen in solid SNEDDS poses great potential in improving the therapeutic efficacy...

  1. 4-N-pyridin-2-yl-benzamide nanotubes compatible with mouse stem cell and oral delivery in Drosophila

    Energy Technology Data Exchange (ETDEWEB)

    Yadav, Jhillu S; Das, Pragna P; Bag, Indira; Krishnan, Anita; Jagannadh, Bulusu; Mohapatra, Debendra K; Bhadra, Manika Pal [Division of Organic Chemistry-I, Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007 (India); Lavanya, Madugula P; Bhadra, Utpal [Functional Genomics and Gene Silencing Group, Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007 (India)

    2010-04-16

    p-aminobenzoic acid (PABA), a structural moiety of many commercial drugs, is self-assembled with linker alkyl side chains to form tubular nanostructures. The tubes exhibited fluorescence either intrinsic or from fluorescent molecules embedded in the wall during self-assembly. Uptake and inter-cellular delivery of the conjugated nanotubes in human cancer cells and in mouse embryonic stem cells were demonstrated by fluorescence imaging and flow cytometry. Biocompatibility, cytotoxicity and clearance were monitored both ex vivo in mouse multipotent embryonic stem cells and in vivo in adult Drosophila. Accumulation of nanotubes had no adverse effects and abnormalities on stem cell morphology and proliferation rate. A distinct distribution of two separate nanotubes in various internal organs of Drosophila interprets that accumulation of nanomaterials might be interdependent on the side chain modifications and physiological settings of cell or tissue types. Unlike carbon nanomaterials, exposure of PABA nanotubes does not produce any hazards including locomotion defects and mortality of adult flies. Despite differential uptake and clearance from multiple live tissues, the use of self-assembled nanotubes can add new dimensions and scope to the development of dual-purpose oral carriers for the fulfilment of many biological promises.

  2. 4-N-pyridin-2-yl-benzamide nanotubes compatible with mouse stem cell and oral delivery in Drosophila

    International Nuclear Information System (INIS)

    Yadav, Jhillu S; Das, Pragna P; Bag, Indira; Krishnan, Anita; Jagannadh, Bulusu; Mohapatra, Debendra K; Bhadra, Manika Pal; Lavanya, Madugula P; Bhadra, Utpal

    2010-01-01

    p-aminobenzoic acid (PABA), a structural moiety of many commercial drugs, is self-assembled with linker alkyl side chains to form tubular nanostructures. The tubes exhibited fluorescence either intrinsic or from fluorescent molecules embedded in the wall during self-assembly. Uptake and inter-cellular delivery of the conjugated nanotubes in human cancer cells and in mouse embryonic stem cells were demonstrated by fluorescence imaging and flow cytometry. Biocompatibility, cytotoxicity and clearance were monitored both ex vivo in mouse multipotent embryonic stem cells and in vivo in adult Drosophila. Accumulation of nanotubes had no adverse effects and abnormalities on stem cell morphology and proliferation rate. A distinct distribution of two separate nanotubes in various internal organs of Drosophila interprets that accumulation of nanomaterials might be interdependent on the side chain modifications and physiological settings of cell or tissue types. Unlike carbon nanomaterials, exposure of PABA nanotubes does not produce any hazards including locomotion defects and mortality of adult flies. Despite differential uptake and clearance from multiple live tissues, the use of self-assembled nanotubes can add new dimensions and scope to the development of dual-purpose oral carriers for the fulfilment of many biological promises.

  3. Mucoadhesive hydrogel microparticles based on poly (methacrylic acid-vinyl pyrrolidone)-chitosan for oral drug delivery.

    Science.gov (United States)

    Sajeesh, S; Sharma, Chandra P

    2011-05-01

    The study was aimed at the evaluation of N-vinyl pyrrolidone (NVP) incorporated polymethacrylic acid-chitosan microparticles for oral drug delivery applications. Poly (methacrylic acid)-chitosan (PMC) and poly(methacrylic acid-vinyl pyrrolidone)-chitosan (PMVC) microparticles were prepared by an ionic-gelation method. Mucoadhesion behaviour of these particles was evaluated by ex-vivo adhesion method using freshly excised rat intestinal tissue. Cytotoxicity and absorption enhancing property of PMC and PMVC particles were evaluated on Caco 2 cell monolayers. Protease enzyme inhibition capability and insulin loading/release properties of these hydrogel particles was evaluated under in vitro experimental conditions. Addition of NVP units enhanced the mucoadhesion behavior of PMC particles on isolated rat intestinal tissue. Both PMC and PMVC particles were found non-toxic on Caco 2 cell monolayers and PMC particles was more effective in improving paracellular transport of fluorescent dextran across Caco 2 cell monolayers as compared to PMVC particles. However, protease inhibition efficacy of PMC particles was not significantly affected with NVP addition. NVP incorporation improved the insulin release properties of PMC microparticles at acidic pH. Hydrophilic modification seems to be an interesting approach in improving mucoadhesion capability of PMC microparticles.

  4. CO-DELIVERY OF NATURAL METABOLIC INHIBITORS IN A SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEM FOR IMPROVED ORAL BIOAVAILABILITY OF CURCUMIN

    OpenAIRE

    Grill, Alex E.; Koniar, Brenda; Panyam, Jayanth

    2014-01-01

    In spite of its well-documented anticancer chemopreventive and therapeutic activity, the clinical development of curcumin has been limited by its poor oral bioavailability. Curcumin has low aqueous solubility and undergoes extensive first pass metabolism following oral dosing. We hypothesized that oral bioavailability of curcumin can be enhanced by increasing its absorption and decreasing its metabolic clearance simultaneously. To test this hypothesis, we formulated curcumin with naturally oc...

  5. Optimizing therapeutic efficacy of chemopreventive agents: A critical review of delivery strategies in oral cancer chemoprevention clinical trials

    OpenAIRE

    Andrew S Holpuch; Kashappa-Goud H Desai; Steven P Schwendeman; Susan R Mallery

    2011-01-01

    Due to its characterized progression from recognized premalignant oral epithelial changes (i.e., oral epithelial dysplasia) to invasive cancer, oral squamous cell carcinoma represents an optimal disease for chemopreventive intervention prior to malignant transformation. The primary goal of oral cancer chemoprevention is to reverse, suppress, or inhibit the progression of premalignant lesions to cancer. Over the last several decades, numerous oral cancer chemoprevention clinical trials have as...

  6. Surface display of Clonorchis sinensis enolase on Bacillus subtilis spores potentializes an oral vaccine candidate.

    Science.gov (United States)

    Wang, Xiaoyun; Chen, Wenjun; Tian, Yanli; Mao, Qiang; Lv, Xiaoli; Shang, Mei; Li, Xuerong; Yu, Xinbing; Huang, Yan

    2014-03-10

    Clonorchis sinensis (C. sinensis) infections remain the common public health problem in freshwater fish consumption areas. New effective prevention strategies are still the urgent challenges to control this kind of foodborne infectious disease. The biochemical importance and biological relevance render C. sinensis enolase (Csenolase) as a potential vaccine candidate. In the present study, we constructed Escherichia coli/Bacillus subtilis shuttle genetic engineering system and investigated the potential of Csenolase as an oral vaccine candidate for C. sinensis prevention in different immunization routes. Our results showed that, compared with control groups, both recombinant Csenolase protein and nucleic acid could induce a mixed IgG1/IgG2a immune response when administrated subcutaneously (Psinensis infection. Csenolase derived oral vaccine conferred worm reduction rate and egg reduction rate at 60.07% (Psinensis prevention. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Expression of cytokeratin 18 and 19 in oral potentially malignant disorders: A systematic review

    Directory of Open Access Journals (Sweden)

    Sam Prasad Prabakaran

    2014-01-01

    Full Text Available The aim of this review is to evaluate the expression of cytokeratin 18 and 19 in oral potentially malignant disorders (OPMD. Systematic review was performed using Medline and PubMed. Hand searches were taken from the back references. Articles published till 15 July 2014 were included in the search. The search yielded a total of 20 articles, out of which 16 articles were eliminated, as they did not fulfill the inclusion criteria and 4 articles were included for the final analysis. The available literature showed that cytokeratin 18 and 19 were expressed in all OPMDs. The level of expression varied among different oral, potentially malignant disorders and among different studies.

  8. Novel Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS for Oral Delivery of Olmesartan Medoxomil: Design, Formulation, Pharmacokinetic and Bioavailability Evaluation

    Directory of Open Access Journals (Sweden)

    Ali Nasr

    2016-06-01

    Full Text Available The main purpose of this study was to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS of Olmesartan (OLM for enhancement of its solubility and dissolution rate. In this study, liquid SNEDDS containing Olmesartan was formulated and further developed into a solid form by the spray drying technique using Aerosil 200 as a solid carrier. Based on the preliminary screening of different unloaded SNEDDS formulae, eight formulae of OLM loaded SNEEDS were prepared using Capryol 90, Cremophor RH40 and Transcutol HP as oil, surfactant and cosurfactant, respectively. Results showed that the mean droplet size of all reconstituted SNEDDS was found to be in the nanometric range (14.91–22.97 nm with optimum PDI values (0.036–0.241. All formulae also showed rapid emulsification time (15.46 ± 1.34–24.17 ± 1.47 s, good optical clarity (98.33% ± 0.16%–99.87% ± 0.31% and high drug loading efficiency (96.41% ± 1.20%–99.65% ± 1.11%. TEM analysis revealed the formation of spherical and homogeneous droplets with a size smaller than 50 nm. In vitro release of OLM from SNEDDS formulae showed that more than 90% of OLM released in approximately 90 min. Optimized SNEDDS formulae were selected to be developed into S-SNEDDS using the spray drying technique. The prepared S-SNEDDS formulae were evaluated for flow properties, differential scanning calorimetry (DSC, scanning electron microscopy (SEM, reconstitution properties, drug content and in vitro dissolution study. It was found that S-SNEDDS formulae showed good flow properties and high drug content. Reconstitution properties of S-SNEDDS showed spontaneous self-nanoemulsification and no sign of phase separation. DSC thermograms revealed that OLM was in solubilized form and FTIR supported these findings. SEM photographs showed smooth uniform surface of S-SNEDDS with less aggregation. Results of the in vitro drug release showed that there was great enhancement in the dissolution rate of OLM

  9. Interleukin-2 treatment potentiates induction of oral tolerance in a murine model of autoimmunity.

    OpenAIRE

    Rizzo, L V; Miller-Rivero, N E; Chan, C C; Wiggert, B; Nussenblatt, R B; Caspi, R R

    1994-01-01

    The present study addresses the feasibility of potentiating oral tolerance by immunomanipulation, using the murine model of experimental autoimmune uveoretinitis (EAU) induced by immunization with the retinal antigen interphotoreceptor retinoid binding protein (IRBP). Three feedings of 0.2 mg IRBP every other day before immunization did not protect against EAU, whereas a similar regimen of five doses was protective. However, supplementing the nonprotective 3x regimen with as little as one inj...

  10. Assessment of serum copper, iron and immune complexes in potentially malignant disorders and oral cancer

    Directory of Open Access Journals (Sweden)

    Ritu TIWARI

    Full Text Available Abstract Potentially malignant disorders (PMDs of oral cavity and oral cancer remain a cause of serious concern despite intensive research and development. Diet and immunity have been identified to play a crucial role as modifying factors in these diseases. Our study intended to explore this relationship by estimating and comparing the serum levels of copper, iron and circulating immune complexes (CICs in patients diagnosed with PMDs and oral cancer and normal healthy individuals. In this study, 40 histopathologically diagnosed cases of PMDs and oral cancer were included along with 30 healthy controls and 5 ml of venous blood was drawn using venipuncture. Serum estimation of copper, iron and CIC then followed using the colorimetric and spectrophotometric methods. The data obtained was subjected to statistical analysis using one way ANOVA and Pearson’s Product-Moment Correlation Test. The mean serum copper level was measured as 138.98 ± 10.13µg/100ml in the PMD group and 141.99 ± 21.44 µg/100ml in the oral cancer as compared to 105.5 + 18.81µ/100ml in the controls. The mean serum CIC levels was highest in the oral cancer (9.65 ± 0.16OD470 followed by the PMD group (0.18 + 0.21 OD470 and least in the control group (0.048 ± 0.02OD470. Whereas, the serum levels of iron showed a significant decrease in the PMD group (110.9 ± 10.54 µg/100ml and the oral cancer group (114.29 ± 25.83 µg/100ml as compared with the control group (136.85 ± 14.48 µg/100ml. There was no positive correlation obtained between the three groups with respect to the chosen parameters indicating that the variables were independent of each other. It can be thus be ascertained that trace elements like copper and iron as well as humoral responses (CICs have a close relationship with PMDs and oral cancers.

  11. Convection-enhanced drug delivery to the brain: therapeutic potential and neuropathological considerations.

    Science.gov (United States)

    Barua, Neil U; Gill, Steven S; Love, Seth

    2014-03-01

    Convection-enhanced delivery (CED) describes a direct method of drug delivery to the brain through intraparenchymal microcatheters. By establishing a pressure gradient at the tip of the infusion catheter in order to exploit bulk flow through the interstitial spaces of the brain, CED offers a number of advantages over conventional drug delivery methods-bypass of the blood-brain barrier, targeted distribution through large brain volumes and minimization of systemic side effects. Despite showing early promise, CED is yet to fulfill its potential as a mainstream strategy for the treatment of neurological disease. Substantial research effort has been dedicated to optimize the technology for CED and identify the parameters, which govern successful drug distribution. It seems likely that successful clinical translation of CED will depend on suitable catheter technology being used in combination with drugs with optimal physicochemical characteristics, and on neuropathological analysis in appropriate preclinical models. In this review, we consider the factors most likely to influence the success or failure of CED, and review its application to the treatment of high-grade glioma, Parkinson's disease (PD) and Alzheimer's disease (AD). © 2013 International Society of Neuropathology.

  12. PEGylated Polyamidoamine dendrimer conjugated with tumor homing peptide as a potential targeted delivery system for glioma.

    Science.gov (United States)

    Jiang, Yan; Lv, Lingyan; Shi, Huihui; Hua, Yabing; Lv, Wei; Wang, Xiuzhen; Xin, Hongliang; Xu, Qunwei

    2016-11-01

    Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system (CNS) tumor with a short survival time. The failure of chemotherapy is ascribed to the low transport of chemotherapeutics across the Blood Brain Tumor Barrier (BBTB) and poor penetration into tumor tissue. In order to overcome the two barriers, small nanoparticles with active targeted capability are urgently needed for GBM drug delivery. In this study, we proposed PEGylated Polyamidoamine (PAMAM) dendrimer nanoparticles conjugated with glioma homing peptides (Pep-1) as potential glioma targeting delivery system (Pep-PEG-PAMAM), where PEGylated PAMAM dendrimer nanoparticle was utilized as carrier due to its small size and perfect penetration into tumor and Pep-1 was used to overcome BBTB via interleukin 13 receptor α2 (IL-13Rα2) mediated endocytosis. The preliminary availability and safety of Pep-PEG-PAMAM as a nanocarrier for glioma was evaluated. In vitro results indicated that a significantly higher amount of Pep-PEG-PAMAM was endocytosed by U87 MG cells. In vivo fluorescence imaging of U87MG tumor-bearing mice confirmed that the fluorescence intensity at glioma site of targeted group was 2.02 folds higher than that of untargeted group (**p<0.01), and glioma distribution experiment further revealed that Pep-PEG-PAMAM exhibited a significantly enhanced accumulation and improved penetration at tumor site. In conclusion, Pep-1 modified PAMAM was a promising nanocarrier for targeted delivery of brain glioma. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Effect of curcumin in reducing burning sensation in potentially malignant disorders of oral cavity

    Directory of Open Access Journals (Sweden)

    Nitin Nigam

    2017-01-01

    Full Text Available Introduction: Curcumin, chemically named as diferuloylmethane is a yellow coloured pigment which shows anti inflammatory, antioxidant, pro apoptotic, antibacterial, antiviral and antifungal activities. It suppresses cyclooxygenase, lipooxygenase and other inflammatory mediators and destroys free radicals. Aim: To evaluate the efficacy of curcumin in reducing the burning sensation in potentially malignant disorders of oral cavity. Materials and Methods: 100 subjects diagnosed clinically with potentially malignant disorders of oral cavity were included in this study. The patients were administered commercially available turmeric systemically and topical application of turmeric and honey was advised. Their burning sensation on VAS scale was evaluated after 15 days, and the data was then statistically analysed by Wilcoxon sign rank test. Results: After the treatment there was a significant decrease in VAS scale. The median showed decrease from 7 to 4. The mean value also showed decrease from 6.91 to 3.98. Conclusion: Hence, it is concluded that turmeric and honey showed positive results in reducing burning sensation in potentially malignant disorders of oral cavity.

  14. Potential of Cationic Liposomes as Adjuvants/Delivery Systems for Tuberculosis Subunit Vaccines.

    Science.gov (United States)

    Khademi, Farzad; Taheri, Ramezan Ali; Momtazi-Borojeni, Amir Abbas; Farnoosh, Gholamreza; Johnston, Thomas P; Sahebkar, Amirhossein

    2018-04-27

    The weakness of the BCG vaccine and its highly variable protective efficacy in controlling tuberculosis (TB) in different age groups as well as in different geographic areas has led to intense efforts towards the development and design of novel vaccines. Currently, there are several strategies to develop novel TB vaccines. Each strategy has its advantages and disadvantages. However, the most important of these strategies is the development of subunit vaccines. In recent years, the use of cationic liposome-based vaccines has been considered due to their capacity to elicit strong humoral and cellular immune responses against TB infections. In this review, we aim to evaluate the potential for cationic liposomes to be used as adjuvants/delivery systems for eliciting immune responses against TB subunit vaccines. The present review shows that cationic liposomes have extensive applications either as adjuvants or delivery systems, to promote immune responses against Mycobacterium tuberculosis (Mtb) subunit vaccines. To overcome several limitations of these particles, they were used in combination with other immunostimulatory factors such as TDB, MPL, TDM, and Poly I:C. Cationic liposomes can provide long-term storage of subunit TB vaccines at the injection site, confer strong electrostatic interactions with APCs, potentiate both humoral and cellular (CD4 and CD8) immune responses, and induce a strong memory response by the immune system. Therefore, cationic liposomes can increase the potential of different TB subunit vaccines by serving as adjuvants/delivery systems. These properties suggest the use of cationic liposomes to produce an efficient vaccine against TB infections.

  15. Chitosan and glyceryl monooleate nanostructures containing gemcitabine: potential delivery system for pancreatic cancer treatment.

    Science.gov (United States)

    Trickler, William J; Khurana, Jatin; Nagvekar, Ankita A; Dash, Alekha K

    2010-03-01

    The objectives of this study are to enhance cellular accumulation of gemcitabine with chitosan/glyceryl monooleate (GMO) nanostructures, and to provide significant increase in cell death of human pancreatic cancer cells in vitro. The delivery system was prepared by a multiple emulsion solvent evaporation method. The nanostructure topography, size, and surface charge were determined by atomic force microscopy (AFM), and a zetameter. The cellular accumulation, cellular internalization and cytotoxicity of the nanostructures were evaluated by HPLC, confocal microscopy, or MTT assay in Mia PaCa-2 and BxPC-3 cells. The average particle diameter for 2% and 4% (w/w) drug loaded delivery system were 382.3 +/- 28.6 nm, and 385.2 +/- 16.1 nm, respectively with a surface charge of +21.94 +/- 4.37 and +21.23 +/- 1.46 mV. The MTT cytotoxicity dose-response studies revealed the placebo at/or below 1 mg/ml has no effect on MIA PaCa-2 or BxPC-3 cells. The delivery system demonstrated a significant decrease in the IC50 (3 to 4 log unit shift) in cell survival for gemcitabine nanostructures at 72 and 96 h post-treatment when compared with a solution of gemcitabine alone. The nanostructure reported here can be resuspended in an aqueous medium that demonstrate increased effective treatment compared with gemcitabine treatment alone in an in vitro model of human pancreatic cancer. The drug delivery system demonstrates capability to entrap both hydrophilic and hydrophobic compounds to potentially provide an effective treatment option in human pancreatic cancer.

  16. Low-cost production of proinsulin in tobacco and lettuce chloroplasts for injectable or oral delivery of functional insulin and C-peptide.

    Science.gov (United States)

    Boyhan, Diane; Daniell, Henry

    2011-06-01

    Current treatment for type I diabetes includes delivery of insulin via injection or pump, which is highly invasive and expensive. The production of chloroplast-derived proinsulin should reduce cost and facilitate oral delivery. Therefore, tobacco and lettuce chloroplasts were transformed with the cholera toxin B subunit fused with human proinsulin (A, B, C peptides) containing three furin cleavage sites (CTB-PFx3). Transplastomic lines were confirmed for site-specific integration of transgene and homoplasmy. Old tobacco leaves accumulated proinsulin up to 47% of total leaf protein (TLP). Old lettuce leaves accumulated proinsulin up to 53% TLP. Accumulation was so stable that up to ~40% proinsulin in TLP was observed even in senescent and dried lettuce leaves, facilitating their processing and storage in the field. Based on the yield of only monomers and dimers of proinsulin (3 mg/g leaf, a significant underestimation), with a 50% loss of protein during the purification process, one acre of tobacco could yield up to 20 million daily doses of insulin per year. Proinsulin from tobacco leaves was purified up to 98% using metal affinity chromatography without any His-tag. Furin protease cleaved insulin peptides in vitro. Oral delivery of unprocessed proinsulin bioencapsulated in plant cells or injectable delivery into mice showed reduction in blood glucose levels similar to processed commercial insulin. C-peptide should aid in long-term treatment of diabetic complications including stimulation of nerve and renal functions. Hyper-expression of functional proinsulin and exceptional stability in dehydrated leaves offer a low-cost platform for oral and injectable delivery of cleavable proinsulin. © 2010 The Authors. Plant Biotechnology Journal © 2010 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  17. Surface modification of solid lipid nanoparticles for oral delivery of curcumin: Improvement of bioavailability through enhanced cellular uptake, and lymphatic uptake.

    Science.gov (United States)

    Baek, Jong-Suep; Cho, Cheong-Weon

    2017-08-01

    Curcumin has been reported to exhibit potent anticancer effects. However, poor solubility, bioavailability and stability of curcumin limit its in vivo efficacy for the cancer treatment. Solid lipid nanoparticles (SLN) are a promising delivery system for the enhancement of bioavailability of hydrophobic drugs. However, burst release of drug from SLN in acidic environment limits its usage as oral delivery system. Hence, we prepared N-carboxymethyl chitosan (NCC) coated curcumin-loaded SLN (NCC-SLN) to inhibit the rapid release of curcumin in acidic environment and enhance the bioavailability. The NCC-SLN exhibited suppressed burst release in simulated gastric fluid while sustained release was observed in simulated intestinal fluid. Furthermore, NCC-SLN exhibited increased cytotoxicity and cellular uptake on MCF-7 cells. The lymphatic uptake and oral bioavailability of NCC-SLN were found to be 6.3-fold and 9.5-fold higher than that of curcumin solution, respectively. These results suggest that NCC-SLN could be an efficient oral delivery system for curcumin. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Efficacy of thiolated eudragit microspheres as an oral vaccine delivery system to induce mucosal immunity against enterotoxigenic Escherichia coli in mice.

    Science.gov (United States)

    Lee, Won-Jung; Cha, Seungbin; Shin, Minkyoung; Jung, Myunghwan; Islam, Mohammad Ariful; Cho, Chong-su; Yoo, Han Sang

    2012-05-01

    A vaccine delivery system based on thiolated eudragit microsphere (TEMS) was studied in vivo for its ability to elicit mucosal immunity against enterotoxigenic Escherichia coli (ETEC). Groups of mice were orally immunized with F4 or F18 fimbriae of ETEC and F4 or F18 loaded in TEMS. Mice that were orally administered with F4 or F18 loaded TEMS showed higher antigen-specific IgG antibody responses in serum and antigen-specific IgA in saliva and feces than mice that were immunized with antigens only. In addition, oral vaccination of F4 or F18 loaded TEMS resulted in higher numbers of IgG and IgA antigen-specific antibody secreting cells in the spleen, lamina propria, and Peyer's patches of immunized mice than other groups. Moreover, TEMS administration loaded with F4 or F18 induced mixed Th1 and Th2 type responses based on similarly increased levels of IgG1 and IgG2a. These results suggest that F4 or F18 loaded TEMS may be a promising candidate for an oral vaccine delivery system to elicit systemic and mucosal immunity against ETEC. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Preparation and investigation of Ulex europaeus agglutinin I-conjugated liposomes as potential oral vaccine carriers.

    Science.gov (United States)

    Li, KeXin; Chen, DaWei; Zhao, XiuLi; Hu, HaiYang; Yang, ChunRong; Pang, DaHai

    2011-11-01

    We prepared and optimized Ulex europaeus agglutinin I (UEAI)-modified Bovine serum albumin (BSA)-encapsulating liposomes (UEAI-LIP) as oral vaccine carriers and examined the feasibility of inducing systemic and mucosal immune responses by oral administration of UEAILIP. The prepared systems were characterized in vitro for their average size, zeta potential, encapsulation efficiency (EE%) and conjugation efficiency (CE%). In vitro release studies indicated that the presence of UEAI around the optimized liposomes was able to prevent a burst release of loaded BSA and provide sustained release of the encapsulated protein. In vivo immune-stimulating results in KM mice showed that BSA given intramuscularly generated systemic response only but both systemic and mucosal immune responses could be induced simultaneously in the groups in which BSA-loaded liposomes (LIP) and UEAI-LIP were administered intragastrically. Furthermore, the modification of UEAI on the surface of liposomes could further enhance the IgA and IgG levels obviously. In conclusion, this study demonstrated the high potential of lectin-modified liposomes containing the antigen as carriers for oral vaccine.

  20. Intracellular delivery of potential therapeutic genes: prospects in cancer gene therapy.

    Science.gov (United States)

    Bakhtiar, Athirah; Sayyad, Mustak; Rosli, Rozita; Maruyama, Atsushi; Chowdhury, Ezharul H

    2014-01-01

    Conventional therapies for malignant cancer such as chemotherapy and radiotherapy are associated with poor survival rates owing to the development of cellular resistance to cancer drugs and the lack of targetability, resulting in unwanted adverse effects on healthy cells and necessitating the lowering of therapeutic dose with consequential lower efficacy of the treatment. Gene therapy employing different types of viral and non-viral carriers to transport gene(s) of interest and facilitating production of the desirable therapeutic protein(s) has tremendous prospects in cancer treatments due to the high-level of specificity in therapeutic action of the expressed protein(s) with diminished off-target effects, although cancer cell-specific delivery of transgene(s) still poses some challenges to be addressed. Depending on the potential therapeutic target genes, cancer gene therapy could be categorized into tumor suppressor gene replacement therapy, immune gene therapy and enzyme- or prodrug-based therapy. This review would shed light on the current progress of delivery of potentially therapeutic genes into various cancer cells in vitro and animal models utilizing a variety of viral and non-viral vectors.

  1. Highly lipophilic pluronics-conjugated polyamidoamine dendrimer nanocarriers as potential delivery system for hydrophobic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Thi Tram Chau [Institute of Research and Development, Duy Tan University, Da Nang City 550000 (Viet Nam); Department of Chemical Engineering, Industrial University of HCMC, HCMC 70000 (Viet Nam); Nguyen, Cuu Khoa, E-mail: nckhoavnn@yahoo.com [Department of Materials and Pharmaceutical Chemistry, Vietnam Academy of Science and Technology, HCMC 70000 (Viet Nam); Nguyen, Thi Hiep [Biomedical Engineering Department, International University, National Universities in HCMC, HCMC 70000 (Viet Nam); Tran, Ngoc Quyen, E-mail: tnquyen@iams.vast.vn [Institute of Research and Development, Duy Tan University, Da Nang City 550000 (Viet Nam); Department of Materials and Pharmaceutical Chemistry, Vietnam Academy of Science and Technology, HCMC 70000 (Viet Nam)

    2017-01-01

    In the study, four kinds of pluronics (P123, F68, F127 and F108) with varying hydrophilic-lipophilic balance (HLB) values were modified and conjugated on 4th generation of polyamidoamine dendrimer (PAMAM). The obtained results from FT-IR, {sup 1}H NMR and GPC showed that the pluronics effectively conjugated on the dendrimer. The molecular weight of four PAMAM G4.0-Pluronics and its morphologies are in range of 200.15–377.14 kDa and around 60–180 nm in diameter by TEM, respectively. Loading efficiency and release of hydrophobic fluorouracil (5-FU) anticancer drug were evaluated by HPLC; Interesting that the dendrimer nanocarrier was conjugated with the highly lipophilic pluronic P123 (G4.0-P123) exhibiting a higher drug loading efficiency (up to 76.25%) in comparison with another pluronics. Live/dead fibroblast cell staining assay mentioned that all conjugated nanocarriers are highly biocompatible. The drug-loaded nanocarriers also indicated a highly anti-proliferative activity against MCF-7 breast cancer cell. The obtained results demonstrated a great potential of the highly lipophilic pluronics-conjugated nanocarriers in hydrophobic drugs delivery for biomedical applications. - Highlights: • Biocompatible pluronic-conjugated polyamidoamine dendrimers were prepared at nanoscale for drug delivery. • The dendrimer nanocarrier was decorated with a lipophilic pluronic exhibiting a higher drug loading efficiency. • The pluronic-functionalized nanocarriers demonstrated a great potential for delivering hydrophobic drugs.

  2. The potential of protein-nanomaterial interaction for advanced drug delivery.

    Science.gov (United States)

    Peng, Qiang; Mu, Huiling

    2016-03-10

    Nanomaterials, like nanoparticles, micelles, nano-sheets, nanotubes and quantum dots, have great potentials in biomedical fields. However, their delivery is highly limited by the formation of protein corona upon interaction with endogenous proteins. This new identity, instead of nanomaterial itself, would be the real substance the organs and cells firstly encounter. Consequently, the behavior of nanomaterials in vivo is uncontrollable and some undesired effects may occur, like rapid clearance from blood stream; risk of capillary blockage; loss of targeting capacity; and potential toxicity. Therefore, protein-nanomaterial interaction is a great challenge for nanomaterial systems and should be inhibited. However, this interaction can also be used to functionalize nanomaterials by forming a selected protein corona. Unlike other decoration using exogenous molecules, nanomaterials functionalized by selected protein corona using endogenous proteins would have greater promise for clinical use. In this review, we aim to provide a comprehensive understanding of protein-nanomaterial interaction. Importantly, a discussion about how to use such interaction is launched and some possible applications of such interaction for advanced drug delivery are presented. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Chemopreventive Potential of Flavonoids in Oral Squamous Cell Carcinoma in Human Studies

    Directory of Open Access Journals (Sweden)

    Elena Maria Varoni

    2013-07-01

    Full Text Available Evidence available from nutritional epidemiology has indicated an inverse association between regular consumption of fruits and vegetables and the risk of developing certain types of cancer. In turn, preclinical studies have attributed the health-promoting effects of plant foods to some groups of phytochemicals, by virtue of their many biological activities. In this survey, we briefly examine the chemopreventive potential of flavonoids and flavonoid-rich foods in human oral carcinogenesis. Despite the paucity of data from clinical trials and epidemiological studies, in comparison to in vitro/in vivo investigations, a high level of evidence has been reported for epigallocatechin gallate (EGCG and anthocyanins. These flavonoids, abundant in green tea and black raspberries, respectively, represent promising chemopreventive agents in human oral cancer.

  4. Transdermal drug delivery: approaches and significance

    OpenAIRE

    Murthy, SATHYANARAYANA

    2012-01-01

    S Narasimha MurthyDepartment of Pharmaceutics, The University of Mississippi, USATransdermal drug delivery systems deliver drugs through the skin as an alternative to oral, intravascular, subcutaneous, and transmucosal routes. Potential advantages of transdermal delivery include, but are not limited to, elimination of first-pass metabolism, steady delivery/blood levels, better patient compliance, reduced systemic drug interactions, possible dose intervention, avoidance of medically assisted d...

  5. Expression of Epstein-Barr virus among oral potentially malignant disorders and oral squamous cell carcinomas in the South Indian tobacco-chewing population.

    Science.gov (United States)

    Reddy, Sujatha S; Sharma, Shivani; Mysorekar, Vijaya

    2017-07-01

    Oral cancer is the sixth most common malignancy in the world. Viruses are the causative agents of approximately 10-15% of all cancers worldwide (Cancers, 6, 2014 and 2155). The tumorigenic roles of Epstein-Barr virus in oral cancer are unclear. Literature search results are conflicting and dependent on various factors such as geographical/regional variations, sociocultural lifestyles, dietary habits, chewing/smoking tobacco habit. This study is the first original observation about frequency of Epstein-Barr virus among South Indian tobacco-chewing patients to elucidate its involvement in oral carcinogenesis and to know whether this can be a valuable diagnostic and prognostic indicator. A total number of 75 tobacco chewer subjects aged between 23 and 76 years with histopathologically confirmed oral potentially malignant disorders (25), oral squamous cell carcinoma (25), and age-matched healthy controls (25) formed the study group. Immunohistochemical expression of Epstein-Barr virus latent membrane protein 1 was assessed among cases and healthy controls. Out of the total 75 subjects, six subjects (8%) were positive for Epstein-Barr virus antigen and 69 subjects (92%) negative. The antigen positivity was observed among two cases of moderately differentiated oral squamous cell carcinoma, two cases of leukoplakia, and two healthy controls. No significant association between Epstein-Barr virus positivity was observed among oral potentially malignant disorders and oral squamous cell carcinoma among South Indian tobacco-chewing patients. This can be partially explained by the methodology employed, by the patient population analyzed and different habits in various geographical regions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Probiotics as oral health biotherapeutics.

    Science.gov (United States)

    Saha, Shyamali; Tomaro-Duchesneau, Catherine; Tabrizian, Maryam; Prakash, Satya

    2012-09-01

    Oral health is affected by its resident microorganisms. Three prominent oral disorders are dental caries, gingivitis and periodontitis, with the oral microbiota playing a key role in the initiation/progression of all three. Understanding the microbiota and the diseases they may cause is critical to the development of new therapeutics. This review is focused on probiotics for the prevention and/or treatment of oral diseases. This review describes the oral ecosystem and its correlation with oral health/disease. The pathogenesis and current prevention/treatment strategies of periodontal diseases (PD) and dental caries (DC) are depicted. An introduction of probiotics is followed by an analysis of their role in PD and DC, and their potential role(s) in oral health. Finally, a discussion ensues on the future research directions and limitations of probiotics for oral health. An effective oral probiotic formulation should contribute to the prevention/treatment of microbial diseases of the oral cavity. Understanding the oral microbiota's role in oral disease is important for the development of a therapeutic to prevent/treat dental diseases. However, investigations into clinical efficacy, delivery/dose optimization, mechanism(s) of action and other related parameters are yet to be fully explored. Keeping this in mind, investigations into oral probiotic therapies are proving promising.

  7. Candesartan cilexetil loaded nanodelivery systems for improved oral bioavailability.

    Science.gov (United States)

    Dudhipala, Narendar; Veerabrahma, Kishan

    2017-02-01

    Candesartan cilexetil (CC), an antihypertensive drug, has low oral bioavailability due to poor solubility and hepatic first-pass metabolism. These are major limitations in oral delivery of CC. Several approaches are known to reduce the problems of solubility and improve the bioavailability of CC. Among various approaches, nanotechnology-based delivery of CC has potential to overcome the challenges associated with the oral administration. This review focuses on various nano-based delivery systems available and tried for improving the aqueous solubility, dissolution and consequently bioavailability of CC upon oral administration. Of all, solid lipid nanoparticles appear to be promising delivery system, based on current reported results, for delivery of CC, as this system improved the oral bioavailability and possessed prolonged pharmacodynamic effect.

  8. Administração oral de peptídios e proteínas: III. Aplicação à insulina Oral delivery systems for peptides and proteins: III. Application to insulin

    Directory of Open Access Journals (Sweden)

    Catarina Silva

    2003-03-01

    Full Text Available A insulina é um peptídeo biologicamente ativo, normalmente administrado por via subcutânea, pelos obstáculos que se colocam a sua administração oral. O desenvolvimento de uma forma farmacêutica passível de ser administrada oralmente tem sido razão de uma investigação persistente, acentuada na última década, conforme é descrito. As estratégias utilizadas têm sido muito variadas, a saber, a utilização de inibidores das enzimas proteolíticas, promotores da absorção, modificação química e fórmulas farmacêuticas específicas, como sistemas de partículas, emulsões, sistemas de liberação targeting e sistemas bioadesivos. Embora ainda nenhuma abordagem tenha sido suficientemente eficaz, os resultados são encorajadores. A microencapsulação e, em particular, os métodos que utilizam polímeros naturais, mostram-se promissores neste propósito, pelas características vantajosas que apresentam.Insulin is an important therapeutic protein, generally administered subcutaneously due to the obstacles of oral delivery. A number of different methods have been explored to improve the low oral bioavailability of insulin, particularly in the last decade, namely protease inhibitors, absorption enhancers, chemical modification and the formulation approach which includes particulate systems, emulsions, targeting delivery systems and bioadhesive systems. Although an effective formulation for oral insulin delivery remains to be achieved, the results are encouraging. Microencapsulation has proven to be a promising method of choice, especially when using natural polymers.

  9. Immunohistochemical expression of ezrin in oral potentially malignant disorders-A descriptive study

    Directory of Open Access Journals (Sweden)

    Raghini Mohanraj

    2017-01-01

    Full Text Available Introduction: Ezrin, also known as cytovillin, is a member of the ERM family of protein. Ezrin cross-links actin filament with the plasma membrane. They are involved in the formation of microvilli, cell–cell adhesion, maintenance of cell shape, cell motility, and membrane trafficking. Recent analysis reveals their involvement in signaling pathways. Ezrin is highly expressed in several types of human cancers, and correlation between its immunoreactivity and histopathological data as well as the patient outcome has previously been studied. Objective: The objective of the study was to analyze the immunohistochemical expression pattern of ezrin in oral potentially malignant disorders (OPMDs, namely, oral submucous fibrosis (OSMF with different grades and clinically leucoplakia (hyperkeratosis with various degree of dysplasia and its use as a predictive marker for malignant transformation. Subjects and Methods: Sample size n = 43, histopathologically confirmed cases of OPMDs (13 cases of OSMF with different grades and 30 cases of clinically leukoplakia were retrieved from the Department of Oral and Maxillofacial Pathology. Immunohistochemistry was done using anti-ezrin antibody, and the expression was graded in terms of proportion and intensity. Results: There was a significant expression of ezrin in OPMDs, and its cytoplasmic shift can be used as a predictive marker for malignant transformation. Conclusion: The findings of the current study revealed that the expression of ezrin in OPMDs may be related to the progression of the disease.

  10. Oral delivery of bioencapsulated exendin-4 expressed in chloroplasts lowers blood glucose level in mice and stimulates insulin secretion in beta-TC6 cells.

    Science.gov (United States)

    Kwon, Kwang-Chul; Nityanandam, Ramya; New, James S; Daniell, Henry

    2013-01-01

    Glucagon-like peptide (GLP-1) increases insulin secretion but is rapidly degraded (half-life: 2 min in circulation). GLP-1 analogue, exenatide (Byetta) has a longer half-life (3.3-4 h) with potent insulinotropic effects but requires cold storage, daily abdominal injections with short shelf life. Because patients with diabetes take >60 000 injections in their life time, alternative delivery methods are highly desired. Exenatide is ideal for oral delivery because insulinotropism is glucose dependent, with reduced risk of hypoglycaemia even at higher doses. Therefore, exendin-4 (EX4) was expressed as a cholera toxin B subunit (CTB)-fusion protein in tobacco chloroplasts to facilitate bioencapsulation within plant cells and transmucosal delivery in the gut via GM1 receptors present in the intestinal epithelium. The transgene integration was confirmed by PCR and Southern blot analysis. Expression level of CTB-EX4 reached up to 14.3% of total leaf protein (TLP). Lyophilization of leaf material increased therapeutic protein concentration by 12- to 24-fold, extended their shelf life up to 15 months when stored at room temperature and eliminated microbes present in fresh leaves. The pentameric structure, disulphide bonds and functionality of CTB-EX4 were well preserved in lyophilized materials. Chloroplast-derived CTB-EX4 showed increased insulin secretion similar to the commercial EX4 in beta-TC6, a mouse pancreatic cell line. Even when 5000-fold excess dose of CTB-EX4 was orally delivered, it stimulated insulin secretion similar to the intraperitoneal injection of commercial EX4 but did not cause hypoglycaemia in mice. Oral delivery of the bioencapsulated EX4 should eliminate injections, increase patient compliance/convenience and significantly lower their cost. © 2012 The Authors Plant Biotechnology Journal © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  11. Nanoparticles Engineered from Lecithin-in-Water Emulsions As A Potential Delivery System for Docetaxel

    Science.gov (United States)

    Yanasarn, Nijaporn; Sloat, Brian R.; Cui, Zhengrong

    2009-01-01

    Docetaxel is a potent anti-cancer drug. However, there continues to be a need for alternative docetaxel delivery systems to improve its efficacy. We reported the engineering of a novel spherical nanoparticle formulation (~270 nm) from lecithin-in-water emulsions. Docetaxel can be incorporated into the nanoparticles, and the resultant docetaxel-nanoparticles were stable when stored as an aqueous suspension. The release of the docetaxel from the nanoparticles was likely caused by a combination of diffusion and Case II transport. The docetaxel-in-nanoparticles were more effective in killing tumor cells in culture than free docetaxel. Moreover, the docetaxel-nanoparticles did not cause any significant red blood cell lysis or platelet aggregation in vitro, nor did they induce detectable acute liver damage when injected intravenously into mice. Finally, compared to free docetaxel, the intravenously injected docetaxel-nanoparticles increased the accumulation of the docetaxel in a model tumor in mice by 4.5-fold. These lecithin-based nanoparticles have the potential to be a novel biocompatible and efficacious delivery system for docetaxel. PMID:19524029

  12. Inclusion bodies as potential vehicles for recombinant protein delivery into epithelial cells

    Science.gov (United States)

    2012-01-01

    Background We present the potential of inclusion bodies (IBs) as a protein delivery method for polymeric filamentous proteins. We used as cell factory a strain of E. coli, a conventional host organism, and keratin 14 (K14) as an example of a complex protein. Keratins build the intermediate filament cytoskeleton of all epithelial cells. In order to build filaments, monomeric K14 needs first to dimerize with its binding partner (keratin 5, K5), which is then followed by heterodimer assembly into filaments. Results K14 IBs were electroporated into SW13 cells grown in culture together with a “reporter” plasmid containing EYFP labeled keratin 5 (K5) cDNA. As SW13 cells do not normally express keratins, and keratin filaments are built exclusively of keratin heterodimers (i.e. K5/K14), the short filamentous structures we obtained in this study can only be the result of: a) if both IBs and plasmid DNA are transfected simultaneously into the cell(s); b) once inside the cells, K14 protein is being released from IBs; c) released K14 is functional, able to form heterodimers with EYFP-K5. Conclusions Soluble IBs may be also developed for complex cytoskeletal proteins and used as nanoparticles for their delivery into epithelial cells. PMID:22624805

  13. trans-Double Bond-Containing Liposomes as Potential Carriers for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Giorgia Giacometti

    2017-11-01

    Full Text Available The use of liposomes has been crucial for investigations in biomimetic chemical biology as a membrane model and in medicinal chemistry for drug delivery. Liposomes are made of phospholipids whose biophysical characteristics strongly depend on the type of fatty acid moiety, where natural unsaturated lipids always have the double bond geometry in the cis configuration. The influence of lipid double bond configuration had not been considered so far with respect to the competence of liposomes in delivery. We were interested in evaluating possible changes in the molecular properties induced by the conversion of the double bond from cis to trans geometry. Here we report on the effects of the addition of trans-phospholipids supplied in different amounts to other liposome constituents (cholesterol, neutral phospholipids and cationic surfactants, on the size, ζ-potential and stability of liposomal formulations and on their ability to encapsulate two dyes such as rhodamine B and fluorescein. From a biotechnological point of view, trans-containing liposomes proved to have different characteristics from those containing the cis analogues, and to influence the incorporation and release of the dyes. These results open new perspectives in the use of the unnatural lipid geometry, for the purpose of changing liposome behavior and/or of obtaining molecular interferences, also in view of synergic effects of cell toxicity, especially in antitumoral strategies.

  14. The pharmacokinetic study on the mechanism of toxicity attenuation of rhubarb total free anthraquinone oral colon-specific drug delivery system.

    Science.gov (United States)

    Zhang, Lin; Chang, Jin-hua; Zhang, Bao-qi; Liu, Xi-gang; Liu, Pei; Xue, He-fei; Liu, Li-yan; Fu, Qiang; Zhu, Meng; Liu, Cui-zhe

    2015-07-01

    Rhubarb is commonly used as laxatives in Asian countries, of which anthraquinones are the major active ingredients, but there are an increased number of concerns regarding the nephrotoxicity of anthraquinones. In this study, we compared the pharmacokinetic characteristics of rhubarb anthraquinones in rats after orally administered with rhubarb and rhubarb total free anthraquinone oral colon-specific drug delivery granules (RTFA-OCDD-GN), and then explained why these granules could reduce the nephrotoxicity of anthraquinones when they produced purgative efficacy. A sensitive and reliable high performance liquid chromatography (HPLC) method has been fully validated for simultaneous determination of the five active components of rhubarb, and successfully applied to investigate and compare the remarkable differences in pharmacokinetic study of rhubarb anthraquinones after orally administered with rhubarb and RTFA-OCDD-GN. The results showed that, compared with rhubarb group, the AUC, Cmax, t1/2z and Vz/F of aloe-emodin, rhein, emodin and chrysophanol in rats receiving the RTFA-OCDD-GN were significantly decreased, and the Tmax of the four analytes was prolonged. Moreover, the Tmax of rhein, the Cmax of chrysophanol and emodin all have significant differences (Panthraquinone prototype excretion rates in urine and feces of aloe-emodin, rhein, emodin, chrysophanol and physcion were all increased. These findings suggested that oral colon-specific drug delivery technology made anthraquinone aglycone to colon-specific release after oral administration. This allowed anthraquinones to not only play the corresponding purgative effect but also avoid intestinal absorption and promote excretion. And thereby greatly reduced the nephrotoxicity of rhubarb. The result is a new breakthrough in rhubarb toxicity attenuated research. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Hyaluronic Acid Graft Copolymers with Cleavable Arms as Potential Intravitreal Drug Delivery Vehicles.

    Science.gov (United States)

    Borke, Tina; Najberg, Mathie; Ilina, Polina; Bhattacharya, Madhushree; Urtti, Arto; Tenhu, Heikki; Hietala, Sami

    2018-01-01

    Treatment of retinal diseases currently demands frequent intravitreal injections due to rapid clearance of the therapeutics. The use of high molecular weight polymers can extend the residence time in the vitreous and prolong the injection intervals. This study reports a water soluble graft copolymer as a potential vehicle for sustained intravitreal drug delivery. The copolymer features a high molecular weight hyaluronic acid (HA) backbone and poly(glyceryl glycerol) (PGG) side chains attached via hydrolysable ester linkers. PGG, a polyether with 1,2-diol groups in every repeating unit available for conjugation, serves as a detachable carrier. The influence of synthesis conditions and incubation in physiological media on the molecular weight of HA is studied. The cleavage of the PGG grafts from the HA backbone is quantified and polymer-from-polymer release kinetics are determined. The biocompatibility of the materials is tested in different cell cultures. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. An albumin-oligonucleotide assembly for potential combinatorial drug delivery and half-life extension applications

    DEFF Research Database (Denmark)

    Kuhlmann, Matthias; Hamming, Jonas Bohn Refslund; Voldum, Anders

    2017-01-01

    The long blood circulatory property of human serum albumin, due to engagement with the cellular recycling neonatal Fc receptor (FcRn), is an attractive drug half-life extension enabling technology. This work describes a novel site-specific albumin double-stranded (ds) DNA assembly approach, in wh...... technology platform that offers potential combinatorial drug delivery and half-life extension applications.......The long blood circulatory property of human serum albumin, due to engagement with the cellular recycling neonatal Fc receptor (FcRn), is an attractive drug half-life extension enabling technology. This work describes a novel site-specific albumin double-stranded (ds) DNA assembly approach......, in which the 3' or 5' end maleimide-derivatized oligodeoxynucleotides are conjugated to albumin cysteine at position 34 (cys34) and annealed with complementary strands to allow single site-specific protein modification with functionalized ds oligodeoxynucleotides. Electrophoretic gel shift assays...

  17. Suppression of inhibitor formation against FVIII in a murine model of hemophilia A by oral delivery of antigens bioencapsulated in plant cells.

    Science.gov (United States)

    Sherman, Alexandra; Su, Jin; Lin, Shina; Wang, Xiaomei; Herzog, Roland W; Daniell, Henry

    2014-09-04

    Hemophilia A is the X-linked bleeding disorder caused by deficiency of coagulation factor VIII (FVIII). To address serious complications of inhibitory antibody formation in current replacement therapy, we created tobacco transplastomic lines expressing FVIII antigens, heavy chain (HC) and C2, fused with the transmucosal carrier, cholera toxin B subunit. Cholera toxin B-HC and cholera toxin B-C2 fusion proteins expressed up to 80 or 370 µg/g in fresh leaves, assembled into pentameric forms, and bound to GM1 receptors. Protection of FVIII antigen through bioencapsulation in plant cells and oral delivery to the gut immune system was confirmed by immunostaining. Feeding of HC/C2 mixture substantially suppressed T helper cell responses and inhibitor formation against FVIII in mice of 2 different strain backgrounds with hemophilia A. Prolonged oral delivery was required to control inhibitor formation long-term. Substantial reduction of inhibitor titers in preimmune mice demonstrated that the protocol could also reverse inhibitor formation. Gene expression and flow cytometry analyses showed upregulation of immune suppressive cytokines (transforming growth factor β and interleukin 10). Adoptive transfer experiments confirmed an active suppression mechanism and revealed induction of CD4(+)CD25(+) and CD4(+)CD25(-) T cells that potently suppressed anti-FVIII formation. In sum, these data support plant cell-based oral tolerance for suppression of inhibitor formation against FVIII. © 2014 by The American Society of Hematology.

  18. Enhancing oral vaccine potency by targeting intestinal M cells.

    Directory of Open Access Journals (Sweden)

    Ali Azizi

    2010-11-01

    Full Text Available The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells.

  19. Multiplexed and Switchable Release of Distinct Fluids from Microneedle Platforms via Conducting Polymer Nanoactuators for Potential Drug Delivery

    Science.gov (United States)

    Valdés-Ramírez, Gabriela; Windmiller, Joshua R.; Claussen, Jonathan C.; Martinez, Alexandra G.; Kuralay, Filiz; Zhou, Ming; Zhou, Nandi; Polsky, Ronen; Miller, Philip R.; Narayan, Roger; Wang, Joseph

    2013-01-01

    We report on the development of a microneedle-based multiplexed drug delivery actuator that enables the controlled delivery of multiple therapeutic agents. Two individually-addressable channels on a single microneedle array, each paired with its own reservoir and conducting polymer nanoactuator, are used to deliver various permutations of two unique chemical species. Upon application of suitable redox potentials to the selected actuator, the conducting polymer is able to undergo reversible volume changes, thereby serving to release a model chemical agent in a controlled fashion through the corresponding microneedle channels. Time-lapse videos offer direct visualization and characterization of the membrane switching capability and, along with calibration investigations, confirm the ability of the device to alternate the delivery of multiple reagents from individual microneedles of the array with higher precision and temporal resolution than conventional drug delivery actuators. Analytical modeling offers prediction of the volumetric flow rate through a single microneedle and accordingly can be used to assist in the design of subsequent microneedle arrays. The robust solid-state design and lack of mechanical components circumvent reliability issues that challenge fragile conventional microelectromechanical drug delivery devices. This proof-of-concept study demonstrates the potential of the drug delivery actuator system to aid in the rapid administration of multiple therapeutic agents and indicates the potential to counteract diverse biomedical conditions. PMID:24174709

  20. Probiotics in the Space Food System: Delivery, Microgravity Effects, and the Potential Benefit to Crew Health

    Science.gov (United States)

    Castro, S. L.; Ott, C. M.; Douglas, G. L.

    2014-01-01

    As mission distance and duration increase, the need grows for non-invasive disease prevention and immunomodulation, especially given the limited medical response capability expected for these missions and the immune dysregulation documented in crew. Additionally, changes in diet, lifestyle, antibiotic usage, and the environmental stresses during spaceflight may alter crewmembers' intestinal microbiome. The addition of probiotic bacteria to the space food system is expected to confer immunostimulatory benefits on crewmembers, with the potential to counteract the immune dysregulation that has been documented in spaceflight. Based on previous studies that demonstrated unique microbiological responses to the low shear environment of spaceflight, probiotic organisms hold the potential to induce enhanced beneficial responses through mechanisms, such as beneficial interactions with human immune cells and repression of colonization of pathogens on the mucosa. The work presented here will begin to address two research gaps related to providing probiotics in spaceflight: 1) delivery, and 2) the effect of the low shear microgravity environment on probiotic attributes. The probiotic Lactobacillus acidophilus was selected for investigation due to its wide commercial use and documented benefits that include inhibition of virulence related gene expression in pathogens and mucosal stimulation of immune cells. The delivery system for probiotics has not been determined for spaceflight, where the food system is shelf stable and the lack of refrigeration prevents the use of traditional dairy delivery methods. In order to demonstrate the potential of the space food system to deliver viable probiotic bacteria to crewmembers, the probiotic L. acidophilus was packaged in high barrier flight packaging in nonfat dry milk (NFDM) or retained in commercial capsule form. Viable cells were enumerated over 8 months of storage at 22, 4, and -80ºC. The survival of L. acidophilus rehydrated in NFDM

  1. Pharmaceutical characterization of novel tenofovir liposomal formulations for enhanced oral drug delivery: in vitro pharmaceutics and Caco-2 permeability investigations

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    Spinks CB

    2017-02-01

    calibration curves were linear with r2 > 0.9995 over the analytical range of 1–10 µg/mL. Inter- and intraday accuracy and precision values ranged from 95% to 101% and 0.3% to 2.6%, respectively. The method was determined to be specific and robust. Regarding the potential of the prepared vectors to potentiate tenofovir permeability through the Caco-2 model, a 10-fold increase in tenofovir apparent permeability was observed compared to its oral solution. In conclusion, this novel and validated method was successfully applied to characterize both in vitro encapsulation efficiency and Caco-2 permeability transport for the pharmaceutical assessment of novel tenofovir formulations. Keywords: liposomes, tenofovir, targeting, chromatography, entrapment, permeation

  2. Plant and Fungal Food Components with Potential Activity on the Development of Microbial Oral Diseases

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    Maria Daglia

    2011-01-01

    Full Text Available This paper reports the content in macronutrients, free sugars, polyphenols, and inorganic ions, known to exert any positive or negative action on microbial oral disease such as caries and gingivitis, of seven food/beverages (red chicory, mushroom, raspberry, green and black tea, cranberry juice, dark beer. Tea leaves resulted the richest material in all the detected ions, anyway tea beverages resulted the richest just in fluoride. The highest content in zinc was in chicory, raspberry and mushroom. Raspberry is the richest food in strontium and boron, beer in selenium, raspberry and mushroom in copper. Beer, cranberry juice and, especially green and black tea are very rich in polyphenols, confirming these beverages as important sources of such healthy substances. The fractionation, carried out on the basis of the molecular mass (MM, of the water soluble components occurring in raspberry, chicory, and mushroom extracts (which in microbiological assays revealed the highest potential action against oral pathogens, showed that both the high and low MM fractions are active, with the low MM fractions displaying the highest potential action for all the fractionated extracts. Our findings show that more compounds that can play a different active role occur in these foods.

  3. Potential drug-drug interactions with direct oral anticoagulants in elderly hospitalized patients.

    Science.gov (United States)

    Forbes, Heather L; Polasek, Thomas M

    2017-10-01

    To determine the prevalence and nature of potential drug-drug interactions (DDIs) with direct oral anticoagulants (DOACs) in elderly hospitalized patients. This was a retrospective observational study. Inclusion criteria were: aged over 65 years; taking apixaban, rivaroxaban or dabigatran; and admitted to the Repatriation General Hospital between April 2014 and July 2015. A list of clinically relevant 'perpetrator' drugs was compiled from product information, the Australian Medicines Handbook, the Australian National Prescribing Service resources, and local health network guidelines. The prevalence and nature of potential DDIs with DOACs was determined by comparing inpatient drug charts with the list of perpetrator drugs. There were 122 patients in the study with a mean age of 82 years. Most patients had nonvalvular atrial fibrillation and were taking DOACs to prevent thrombotic stroke (83%). Overall, 45 patients (37%) had a total of 54 potential DDIs. Thirty-five patients had potential pharmacodynamic DDIs with antidepressants, nonsteroidal anti-inflammatory drugs and antiplatelets (35/122, 29%). Nineteen patients had potential pharmacokinetic DDIs (19/122, 16%). Of these, 68% (13/19) were taking drugs that increase DOAC plasma concentrations (amiodarone, erythromycin, diltiazem or verapamil) and 32% (6/19) were taking drugs that decrease DOAC plasma concentrations (carbamazepine, primidone or phenytoin). There were no cases of patients taking contraindicated interacting drugs. Potential DDIs with DOACs in elderly hospital inpatients are relatively common, particularly interactions that may increase the risk of bleeding. The risk-benefit ratio of DOACs in elderly patients on polypharmacy should always be carefully considered.

  4. Potential role of p21 Activated Kinase 1 (PAK1) in the invasion and motility of oral cancer cells

    International Nuclear Information System (INIS)

    Parvathy, Muraleedharan; Sreeja, Sreeharshan; Kumar, Rakesh; Pillai, Madhavan Radhakrishna

    2016-01-01

    Oral cancer malignancy consists of uncontrolled division of cells primarily in and around the floor of the oral cavity, gingiva, oropharynx, lower lip and base of the tongue. According to GLOBOCAN 2012 report, oral cancer is one of the most common cancers among males and females in India. Even though significant advancements have been made in the field of oral cancer treatment modalities, the overall prognosis for the patients has not improved in the past few decades and hence, this demands a new thrust for the identification of novel therapeutic targets in oral cancer. p21 Activated Kinases (PAKs) are potential therapeutic targets that are involved in numerous physiological functions. PAKs are serine-threonine kinases and they serve as important regulators of cytoskeletal dynamics and cell motility, transcription through MAP kinase cascades, death and survival signalling, and cell-cycle progression. Although PAKs are known to play crucial roles in cancer progression, the role and clinical significance of PAKs in oral cancer remains poorly understood. Our results suggest that PAK1 is over-expressed in oral cancer cell lines. Stimulation of Oral Squamous Cell Carcinoma (OSCC) cells with serum growth factors leads to PAK1 re-localization and might cause a profound cytoskeletal remodelling. PAK1 was also found to be involved in the invasion, migration and cytoskeletal remodelling of OSCC cells. Our study revealed that PAK1 may play a crucial role in the progression of OSCC. Studying the role of PAK1 and its substrates is likely to enhance our understanding of oral carcinogenesis and potential therapeutic value of PAKs in oral cancer. The online version of this article (doi:10.1186/s12885-016-2263-8) contains supplementary material, which is available to authorized users

  5. Preparation and characterization of silk fibroin as a biomaterial with potential for drug delivery

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    Zhang Hao

    2012-06-01

    Full Text Available Abstract Background Degummed silk fibroin from Bombyx mori (silkworm has potential carrier capabilities for drug delivery in humans; however, the processing methods have yet to be comparatively analyzed to determine the differential effects on the silk protein properties, including crystalline structure and activity. Methods In this study, we treated degummed silk with four kinds of calcium-alcohol solutions, and performed secondary structure measurements and enzyme activity test to distinguish the differences between the regenerated fibroins and degummed silk fibroin. Results Gel electrophoresis analysis revealed that Ca(NO32-methanol, Ca(NO32-ethanol, or CaCl2-methanol treatments produced more lower molecular weights of silk fibroin than CaCl2-ethanol. X-ray diffraction and Fourier-transform infrared spectroscopy showed that CaCl2-ethanol produced a crystalline structure with more silk I (α-form, type II β-turn, while the other treatments produced more silk II (β-form, anti-parallel β-pleated sheet. Solid-State 13C cross polarization and magic angle spinning-nuclear magnetic resonance measurements suggested that regenerated fibroins from CaCl2-ethanol were nearly identical to degummed silk fibroin, while the other treatments produced fibroins with significantly different chemical shifts. Finally, enzyme activity test indicated that silk fibroins from CaCl2-ethanol had higher activity when linked to a known chemotherapeutic drug, L-asparaginase, than the fibroins from other treatments. Conclusions Collectively, these results suggest that the CaCl2-ethanol processing method produces silk fibroin with biomaterial properties that are appropriate for drug delivery.

  6. Potential Compounds for Oral Cancer Treatment: Resveratrol, Nimbolide, Lovastatin, Bortezomib, Vorinostat, Berberine, Pterostilbene, Deguelin, Andrographolide, and Colchicine.

    Directory of Open Access Journals (Sweden)

    Saurabh Bundela

    Full Text Available Oral cancer is one of the main causes of cancer-related deaths in South-Asian countries. There are very limited treatment options available for oral cancer. Research endeavors focused on discovery and development of novel therapies for oral cancer, is necessary to control the ever rising oral cancer related mortalities. We mined the large pool of compounds from the publicly available compound databases, to identify potential therapeutic compounds for oral cancer. Over 84 million compounds were screened for the possible anti-cancer activity by custom build SVM classifier. The molecular targets of the predicted anti-cancer compounds were mined from reliable sources like experimental bioassays studies associated with the compound, and from protein-compound interaction databases. Therapeutic compounds from DrugBank, and a list of natural anti-cancer compounds derived from literature mining of published studies, were used for building partial least squares regression model. The regression model thus built, was used for the estimation of oral cancer specific weights based on the molecular targets. These weights were used to compute scores for screening the predicted anti-cancer compounds for their potential to treat oral cancer. The list of potential compounds was annotated with corresponding physicochemical properties, cancer specific bioactivity evidences, and literature evidences. In all, 288 compounds with the potential to treat oral cancer were identified in the current study. The majority of the compounds in this list are natural products, which are well-tolerated and have minimal side-effects compared to the synthetic counterparts. Some of the potential therapeutic compounds identified in the current study are resveratrol, nimbolide, lovastatin, bortezomib, vorinostat, berberine, pterostilbene, deguelin, andrographolide, and colchicine.

  7. Potential Compounds for Oral Cancer Treatment: Resveratrol, Nimbolide, Lovastatin, Bortezomib, Vorinostat, Berberine, Pterostilbene, Deguelin, Andrographolide, and Colchicine

    Science.gov (United States)

    Bundela, Saurabh; Sharma, Anjana; Bisen, Prakash S.

    2015-01-01

    Oral cancer is one of the main causes of cancer-related deaths in South-Asian countries. There are very limited treatment options available for oral cancer. Research endeavors focused on discovery and development of novel therapies for oral cancer, is necessary to control the ever rising oral cancer related mortalities. We mined the large pool of compounds from the publicly available compound databases, to identify potential therapeutic compounds for oral cancer. Over 84 million compounds were screened for the possible anti-cancer activity by custom build SVM classifier. The molecular targets of the predicted anti-cancer compounds were mined from reliable sources like experimental bioassays studies associated with the compound, and from protein-compound interaction databases. Therapeutic compounds from DrugBank, and a list of natural anti-cancer compounds derived from literature mining of published studies, were used for building partial least squares regression model. The regression model thus built, was used for the estimation of oral cancer specific weights based on the molecular targets. These weights were used to compute scores for screening the predicted anti-cancer compounds for their potential to treat oral cancer. The list of potential compounds was annotated with corresponding physicochemical properties, cancer specific bioactivity evidences, and literature evidences. In all, 288 compounds with the potential to treat oral cancer were identified in the current study. The majority of the compounds in this list are natural products, which are well-tolerated and have minimal side-effects compared to the synthetic counterparts. Some of the potential therapeutic compounds identified in the current study are resveratrol, nimbolide, lovastatin, bortezomib, vorinostat, berberine, pterostilbene, deguelin, andrographolide, and colchicine. PMID:26536350

  8. Bile salts-containing vesicles: promising pharmaceutical carriers for oral delivery of poorly water-soluble drugs and peptide/protein-based therapeutics or vaccines.

    Science.gov (United States)

    Aburahma, Mona Hassan

    2016-07-01

    Most of the new drugs, biological therapeutics (proteins/peptides) and vaccines have poor performance after oral administration due to poor solubility or degradation in the gastrointestinal tract (GIT). Though, vesicular carriers exemplified by liposomes or niosomes can protect the entrapped agent to a certain extent from degradation. Nevertheless, the harsh GIT environment exemplified by low pH, presence of bile salts and enzymes limits their capabilities by destabilizing them. In response to that, more resistant bile salts-containing vesicles (BS-vesicles) were developed by inclusion of bile salts into lipid bilayers constructs. The effectiveness of orally administrated BS-vesicles in improving the performance of vesicles has been demonstrated in researches. Yet, these attempts did not gain considerable attention. This is the first review that provides a comprehensive overview of utilizing BS-vesicles as a promising pharmaceutical carrier with a special focus on their successful applications in oral delivery of therapeutic macromolecules and vaccines. Insights on the possible mechanisms by which BS-vesicles improve the oral bioavailability of the encapsulated drug or immunological response of entrapped vaccine are explained. In addition, methods adopted to prepare and characterize BS-vesicles are described. Finally, the gap in the scientific researches tackling BS-vesicles that needs to be addressed is highlighted.

  9. Evaluation of Potential Risk Factors that contribute to Malignant Transformation of Oral Lichen Planus: A Literature Review.

    Science.gov (United States)

    Agha-Hosseini, Farzaneh; Sheykhbahaei, Nafiseh; SadrZadeh-Afshar, Maryam-Sadat

    2016-08-01

    Many studies have suggested that a lesion originally diagnosed as oral lichen planus (OLP) has different possibilities of undergoing malignant transformation in time, although these findings remain a controversial issue; for example, some studies reported different values of potential malignancy of OLP. World Health Organization (WHO) classifies OLP as a "potentially malignant disorder" with unspecified malignant transformation risk, and suggests that OLP patients should be closely monitored. Numerous studies have attempted to confirm the malignant transformation potential of OLP. The Cochrane Controlled Trials Register, Medline and EMBASE databases, PubMed, Google Scholar, Ovid, Up To Date, BMJ Clinical Evidence, MD Consult, and Science Direct were searched for papers published between 1997 and 2015. The medical subject heading search terms were "lichen planus," "oral lichen planus," "erosive oral lichen planus," "dysplasia," "oral precancerous condition," "oral premalignant condition," oral cancer, oral squamous cell carcinoma (OSCC), and atrophic lichen planus. A total of 120 English language abstracts were reviewed, and 50 relevant articles identified. Because of the extensive literature on the association between OLP and SCC, we have divided the data into genetic and non-genetic factors for more accurate assessment. In this evidence base, malignant transformation ranges from 0 to 37% with a mean of 4.59%. The highest rate of malignancy was noted in erythematosus and erosive lesions. In this way, follow-up of OLP patients could be carried out more efficiently and appropriately. Oral lichen planus is a premalignant lesion. All types of OLP in any site of oral mucosa must be monitored regularly.

  10. Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential

    International Nuclear Information System (INIS)

    Song, Kai; Song, Yong; Zhao, Xiao-Ping; Shen, Hui; Wang, Meng; Yan, Ting-lin; Liu, Ke; Shang, Zheng-jun

    2014-01-01

    Most previous studies have linked cancer–macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression. - Highlights: • The fusion events between oral cancer and endothelial cells undergo nuclear fusion. • The resulting hybrid cells acquire a new property of drug resistance. • The resulting hybrid cells express the markers of both parental cells (i.e. vimentin and cytokeratin 18). • The hybrid cells contribute to tumor repopulation in vivo

  11. Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kai [Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Shandong Province (China); The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Song, Yong [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Department of Stomatology, Liu Zhou People' s Hospital, Guangxi (China); Zhao, Xiao-Ping; Shen, Hui; Wang, Meng; Yan, Ting-lin [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Liu, Ke, E-mail: liuke.1999@aliyun.com [Department of Oral and Maxillofacial-Head and Neck oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Shang, Zheng-jun, E-mail: shangzhengjun@hotmail.com [Department of Oral and Maxillofacial-Head and Neck oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China)

    2014-10-15

    Most previous studies have linked cancer–macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression. - Highlights: • The fusion events between oral cancer and endothelial cells undergo nuclear fusion. • The resulting hybrid cells acquire a new property of drug resistance. • The resulting hybrid cells express the markers of both parental cells (i.e. vimentin and cytokeratin 18). • The hybrid cells contribute to tumor repopulation in vivo.

  12. Oral delivery of the Sj23LHD-GST antigen by Salmonella typhimurium type III secretion system protects against Schistosoma japonicum infection in mice.

    Directory of Open Access Journals (Sweden)

    Guo Chen

    2011-09-01

    Full Text Available BACKGROUND: Schistosomiasis japonica is a zoonotic parasitic disease and oral vaccine delivery system would be benefit for prevention of this disease. Although attenuated salmonella has been used as an antigen expression vector for oral vaccine development, the membrane-bound vacuoles in which bacteria reside hinders the presentation of expressed heterologous antigens to the major histocompatibility complex (MHC molecules. The present work used an attenuated Salmonella typhimurium strain VNP20009 to secretory expression of Sj23LHDGST bivalent antigen from Schistosoma japonicum and tested the protective efficacy against S. japonicum infection in orally immunized mice. METHODOLOGY/PRINCIPAL FINDINGS: Promoters (nirB or pagC were used to express the antigen (Sj23LHDGST and the Salmonella type III or α-hemolysin secretion system was employed to secrete it. The immunoblotting analysis and fluorescent microscopy revealed that the antigen was effectively expressed and delivered to the cytosol of macrophages in vitro. Among recombinant vaccine strains, an engineered VNP20009 which expressed the antigen by nirB promoter and secreted it through type III secretion system (nirB-sopE(1-104-Sj23LHD-GST efficiently protected against S. japonicum infection in a mouse model. This strain elicited a predominantly IgG(2a antibody response and a markedly increase in the production of IL-12 and IFN-γ. The flow cytometric analysis demonstrated that this strain caused T cell activation as evidenced by significantly increased expression of CD44 and CD69. CONCLUSION/SIGNIFICANCE: Oral delivery of antigen by nirB-driven Salmonella typhimurium type III secretion system is a novel, safe, inexpensive, efficient and convenient approach for schistosome vaccine development.

  13. Epidermal growth factor (EGF) as a potential targeting agent for delivery of boron to malignant gliomas

    International Nuclear Information System (INIS)

    Capala, J.; Barth, R.F.; Adams, D.M.; Bailey, M.Q.; Soloway, A.H.; Carlsson, J.

    1994-01-01

    The majority of high grade gliomas express an amplified epidermal growth factor receptor (EGFR) gene, and this often is associated with an increase in cell surface receptor expression. The rapid internalization and degradation of EGF-EGFR complexes, as well as their high affinity make EGF a potential targeting agent for delivery of 10 B to tumor cells with an amplified number of EGFR. Human glioma cells can expresses as many as 10 5 -10 6 EGF receptors per cell, and if these could be saturated with boronated EGF, then > 10 8 boron atoms would be delivered per cell. Since EGF has a comparatively low molecular weight (∼ 6 kD), this has allowed us to construct relatively small bioconjugates containing ∼ 900 boron atoms per EGF molecule 3 , which also had high affinity for EGFR on tumor cells. In the present study, the feasibility of using EGF receptors as a potential target for therapy of gliomas was investigated by in vivo scintigraphic studies using 131 I- or 99m T c -labeled EGF in a rat brain tumor model. Our results indicate that intratumorally delivered boron- EGF conjugates might be useful for targeting EGFR on glioma cells if the boron containing moiety of the conjugates persisted intracellularly. Further studies are required, however, to determine if this approach can be used for BNCT of the rat glioma

  14. Long-term antibiotic delivery by chitosan-based composite coatings with bone regenerative potential

    Science.gov (United States)

    Ordikhani, F.; Simchi, A.

    2014-10-01

    Composite coatings with bone-bioactivity and drug-eluting capacity are considered as promising materials for titanium bone implants. In this work, drug-eluting chitosan-bioactive glass coatings were fabricated by a single-step electrophoretic deposition technique. Drug-loading and -releasing capacity of the composite coatings were carried out using the vancomycin antibiotic. Uniform coatings with a thickness of ∼55 μm containing 23.7 wt% bioactive glass particles and various amounts of the antibiotic (380-630 μg/cm2) were produced. The coatings were bioactive in terms of apatite-forming ability in simulated body fluid and showed favorable cell adhesion and growth. In vitro biological tests also indicated that the composite coatings had better cellular affinity than pristine chitosan coatings. The in vitro elution kinetics of the composite coating revealed an initial burst release of around 40% of the drug within the first elution step of 1 h and following by a continuous eluting over 4 weeks, revealing long-term drug-delivering potential. Antibacterial tests using survival assay against Gram-positive Staphylococcus aureus bacteria determined the effect of vancomycin release on reduction of infection risk. Almost no bacteria were survived on the coatings prepared from the EPD suspension containing ≥0.5 g/l vancomycin. The developed chitosan-based composite coatings with bone bioactivity and long-term drug-delivery ability may be potentially useful for metallic implants to reduce infection risk.

  15. Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo

    Directory of Open Access Journals (Sweden)

    Wen-bin He

    2018-01-01

    Full Text Available To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood–brain barrier and promotes synaptic functions in the hippocampus.

  16. Preparation and characterization of mucus-penetrating papain/poly(acrylic acid) nanoparticles for oral drug delivery applications

    International Nuclear Information System (INIS)

    Müller, Christiane; Leithner, Katharina; Hauptstein, Sabine; Hintzen, Fabian; Salvenmoser, Willi; Bernkop-Schnürch, Andreas

    2013-01-01

    Particle diffusion through the intestinal mucosal barrier is restricted by the viscoelastic and adhesive properties of the mucus gel layer, preventing their penetration to the underlying absorptive endothelial cells. To overcome this natural barrier, we developed n