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Sample records for albumin-stabilized nanoparticle formulation

  1. Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery or Gynecological Cancers

    Science.gov (United States)

    2018-02-05

    Cervical Adenosarcoma; Cervical Adenosquamous Carcinoma; Cervical Carcinosarcoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Epithelial Tumor; Malignant Peritoneal Neoplasm; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Skin Melanoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma; Uterine Corpus Carcinosarcoma

  2. Nanoparticle formulations of cisplatin for cancer therapy

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    Duan, Xiaopin; He, Chunbai; Kron, Stephen J.; Lin, Wenbin

    2016-01-01

    The genotoxic agent cisplatin, used alone or in combination with radiation and/or other chemotherapeutic agents, is an important first-line chemotherapy for a broad range of cancers. The clinical utility of cisplatin is limited both by intrinsic and acquired resistance and dose-limiting normal tissue toxicity. That cisplatin shows little selectivity for tumor versus normal tissue may be a critical factor limiting its value. To overcome the low therapeutic ratio of the free drug, macromolecular, liposomal and nanoparticle drug delivery systems have been explored toward leveraging the enhanced permeability and retention (EPR) effect and promoting delivery of cisplatin to tumors. Here, we survey recent advances in nanoparticle formulations of cisplatin, focusing on agents that show promise in preclinical or clinical settings. PMID:26848041

  3. Cream formulation impact on topical administration of engineered colloidal nanoparticles.

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    Benedetta Santini

    Full Text Available In order to minimize the impact of systemic toxicity of drugs in the treatment of local acute and chronic inflammatory reactions, the achievement of reliable and efficient delivery of therapeutics in/through the skin is highly recommended. While the use of nanoparticles is now an established practice for drug intravenous targeted delivery, their transdermal penetration is still poorly understood and this important administration route remains almost unexplored. In the present study, we have synthesized magnetic (iron oxide nanoparticles (MNP coated with an amphiphilic polymer, developed a water-in-oil emulsion formulation for their topical administration and compared the skin penetration routes with the same nanoparticles deposited as a colloidal suspension. Transmission and scanning electron microscopies provided ultrastructural evidence that the amphiphilic nanoparticles (PMNP cream formulation allowed the efficient penetration through all the skin layers with a controllable kinetics compared to suspension formulation. In addition to the preferential follicular pathway, also the intracellular and intercellular routes were involved. PMNP that crossed all skin layers were quantified by inductively coupled plasma mass spectrometry. The obtained data suggests that combining PMNP amphiphilic character with cream formulation improves the intradermal penetration of nanoparticles. While PMNP administration in living mice via aqueous suspension resulted in preferential nanoparticle capture by phagocytes and migration to draining lymph nodes, cream formulation favored uptake by all the analyzed dermis cell types, including hematopoietic and non-hematopoietic. Unlike aqueous suspension, cream formulation also favored the maintenance of nanoparticles in the dermal architecture avoiding their dispersion and migration to draining lymph nodes via afferent lymphatics.

  4. Cream formulation impact on topical administration of engineered colloidal nanoparticles.

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    Santini, Benedetta; Zanoni, Ivan; Marzi, Roberta; Cigni, Clara; Bedoni, Marzia; Gramatica, Furio; Palugan, Luca; Corsi, Fabio; Granucci, Francesca; Colombo, Miriam

    2015-01-01

    In order to minimize the impact of systemic toxicity of drugs in the treatment of local acute and chronic inflammatory reactions, the achievement of reliable and efficient delivery of therapeutics in/through the skin is highly recommended. While the use of nanoparticles is now an established practice for drug intravenous targeted delivery, their transdermal penetration is still poorly understood and this important administration route remains almost unexplored. In the present study, we have synthesized magnetic (iron oxide) nanoparticles (MNP) coated with an amphiphilic polymer, developed a water-in-oil emulsion formulation for their topical administration and compared the skin penetration routes with the same nanoparticles deposited as a colloidal suspension. Transmission and scanning electron microscopies provided ultrastructural evidence that the amphiphilic nanoparticles (PMNP) cream formulation allowed the efficient penetration through all the skin layers with a controllable kinetics compared to suspension formulation. In addition to the preferential follicular pathway, also the intracellular and intercellular routes were involved. PMNP that crossed all skin layers were quantified by inductively coupled plasma mass spectrometry. The obtained data suggests that combining PMNP amphiphilic character with cream formulation improves the intradermal penetration of nanoparticles. While PMNP administration in living mice via aqueous suspension resulted in preferential nanoparticle capture by phagocytes and migration to draining lymph nodes, cream formulation favored uptake by all the analyzed dermis cell types, including hematopoietic and non-hematopoietic. Unlike aqueous suspension, cream formulation also favored the maintenance of nanoparticles in the dermal architecture avoiding their dispersion and migration to draining lymph nodes via afferent lymphatics.

  5. Nanoparticles containing curcuminoids (Curcuma longa: development of topical delivery formulation

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    Cristina M. Zamarioli

    Full Text Available Solid lipid nanoparticles incorporating Curcuma longa L., Zingiberaceae, curcuminoids were produced by the hot melt emulsion method. A Box–Behnken factorial design was adopted to study the nanoparticles production at different levels of factors such as the percentage of curcuminoids, time of homogenization and surfactant ratio. The optimized nanoparticles were incorporated into hydrogels for stability, drug release and skin permeation tests. The average nanoparticle sizes were 210.4 nm; the zeta potential of −30.40 ± 4.16; the polydispersivity was 0.222 ± 0.125. The average encapsulation efficiency of curcumin and curcuminoids was 52.92 ± 5.41% and 48.39 ± 6.62%, respectively. Solid lipid nanocapsules were obtained with curcumin load varying from 14.2 to 33.6% and total curcuminoids load as high as 47.7%. The topical formulation containing SLN-Curcuminoids showed good spreadability and stability when subjected to mechanical stress test remained with characteristic color, showed no phase separation and no significant change in pH. As a result of slow release, the nanoparticles were able to avoid permeation or penetration in the pig ear epidermis/dermis during 18 h. The topical formulation is stable and can be used in further in vivo studies for the treatment of inflammatory reactions, in special for radiodermitis.

  6. Physico-chemical separation process of nanoparticles in cosmetic formulations

    International Nuclear Information System (INIS)

    Marín, R. R. Retamal; Babick, F.; Stintz, M.

    2017-01-01

    Understanding the world of nanoparticles, especially their interactions with the environment, begins with their correct detection and successive quantification. To achieve this purpose, one needs to perform correctly developed standard operating procedures (SOPs). Furthermore, the study of nanoparticles frequently requires their characterisation in complex media (e.g. in cosmetic formulations). In this study, a set of sample preparation procedures for the detection and extraction of NMs in emulsion-based formulations is proposed and their performance for model and real-life products is discussed. A separation or extraction of lipid phases is achieved by means of organic solvents. The polarity of the lipid phases is decisive for selecting an optimum solvent. The use of the Hansen Solubility Parameters (HSP) may clearly support this decision. (paper)

  7. Physico-chemical separation process of nanoparticles in cosmetic formulations

    Science.gov (United States)

    Retamal Marín, R. R.; Babick, F.; Stintz, M.

    2017-06-01

    Understanding the world of nanoparticles, especially their interactions with the environment, begins with their correct detection and successive quantification. To achieve this purpose, one needs to perform correctly developed standard operating procedures (SOPs). Furthermore, the study of nanoparticles frequently requires their characterisation in complex media (e.g. in cosmetic formulations). In this study, a set of sample preparation procedures for the detection and extraction of NMs in emulsion-based formulations is proposed and their performance for model and real-life products is discussed. A separation or extraction of lipid phases is achieved by means of organic solvents. The polarity of the lipid phases is decisive for selecting an optimum solvent. The use of the Hansen Solubility Parameters (HSP) may clearly support this decision.

  8. A novel nanoparticle formulation for sustained paclitaxel delivery.

    Science.gov (United States)

    Trickler, W J; Nagvekar, A A; Dash, A K

    2008-01-01

    To develop a novel nanoparticle drug delivery system consisting of chitosan and glyceryl monooleate (GMO) for the delivery of a wide variety of therapeutics including paclitaxel. Chitosan/GMO nanoparticles were prepared by multiple emulsion (o/w/o) solvent evaporation methods. Particle size and surface charge were determined. The morphological characteristics and cellular adhesion were evaluated with surface or transmission electron microscopy methods. The drug loading, encapsulation efficiency, in vitro release and cellular uptake were determined using HPLC methods. The safety and efficacy were evaluated by MTT cytotoxicity assay in human breast cancer cells (MDA-MB-231). These studies provide conceptual proof that chitosan/GMO can form polycationic nano-sized particles (400 to 700 nm). The formulation demonstrates high yields (98 to 100%) and similar entrapment efficiencies. The lyophilized powder can be stored and easily be resuspended in an aqueous matrix. The nanoparticles have a hydrophobic inner-core with a hydrophilic coating that exhibits a significant positive charge and sustained release characteristics. This novel nanoparticle formulation shows evidence of mucoadhesive properties; a fourfold increased cellular uptake and a 1000-fold reduction in the IC(50) of PTX. These advantages allow lower doses of PTX to achieve a therapeutic effect, thus presumably minimizing the adverse side effects.

  9. Nanoparticle-based topical ophthalmic formulations for sustained celecoxib release.

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    Ibrahim, Mohammed Mostafa; Abd-Elgawad, Abd-Elgawad Helmy; Soliman, Osama Abd-Elazeem; Jablonski, Monica M

    2013-03-01

    Celecoxib-loaded NPs were prepared from biodegradable polymers such as poly-ε-caprolactone (PCL), poly(L-lactide) (PLA), and poly(D,L-lactide-co-glycolide) (PLGA) by spontaneous emulsification solvent diffusion method. Different concentrations of polymers, emulsifier, and cosurfactants were used for formulation optimization. Nanoparticles (NPs) were characterized regarding their particle size, PDI, zeta potential, shape, morphology, and drug content. Celecoxib-loaded NPs were incorporated into eye drops, in situ gelling system, and gel and characterized regarding their pH, viscosity, uniformity of drug content, in vitro release, and cytotoxicity. The results of optimized celecoxib-loaded PCL-, PLGA-, and PLA-NPs, respectively, are particle size 119 ± 4, 126.67 ± 7.08, and 135.33 ± 4.15 nm; zeta potential -22.43 ± 2.91, -25.46 ± 2.35, and -31.81 ± 2.54 mV; and encapsulation efficiency 93.44 ± 3.6%, 86.00 ± 1.67%, and 79.04 ± 2.6%. TEM analyses revealed that NPs have spherical shapes with dense core and distinct coat. Formulations possessed uniform drug content with pH and viscosity compatible with the eye. Formulations showed sustained release without any burst effect with the Higuchi non-fickian diffusion mechanism. Cytotoxicity studies revealed that all formulations are nontoxic. Our formulations provide a great deal of flexibility to formulation scientist whereby sizes and zeta potentials of our NPs can be tuned to suit the need using scalable and robust methodologies. These formulations can thus serve as a potential drug delivery system for both anterior and posterior eye diseases. Copyright © 2012 Wiley Periodicals, Inc.

  10. EXPLOITING THE VERSATILITY OF CHOLESTEROL IN NANOPARTICLES FORMULATION.

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    Belletti, D; Grabrucker, A M; Pederzoli, F; Menrath, I; Cappello, V; Vandelli, M A; Forni, F; Tosi, G; Ruozi, B

    2016-09-10

    The biocompatibility of polymers, lipids and surfactants used to formulate is crucial for the safe and sustainable development of nanocarriers (nanoparticles, liposomes, micelles, and other nanocarriers). In this study, Cholesterol (Chol), a typical biocompatible component of liposomal systems, was formulated in Chol-based solid nanoparticles (NPs) stabilized by the action of surfactant and without the help of any other formulative component. Parameters as type (Solutol HS 15, cholic acid sodium salt, poly vinyl alcohol and Pluronic-F68), concentration (0.2; 0.5 and 1% w/v) of surfactant and working temperature (r.t. and 45°C) were optimized and all samples characterized in terms of size, zeta potential, composition, thermal behavior and structure. Results demonstrated that only Pluronic-F68 (0.5% w/v) favors the organization of Chol chains in structured NPs with mean diameter less than 400nm. Moreover, we demonstrated the pivotal role of working temperature on surfactant aggregation state/architecture/stability of Chol-based nanoparticles. At room temperature, Pluronic-F68 exists in solution as individual coils. In this condition, nanoprecipitation of Chol formed the less stable NPs with a 14±3% (w/w) of Pluronic-F68 prevalently on surface (NP-Chol/0.5). On the contrary, working near the critical micelle temperature (CMT) of surfactant (45°C), Chol precipitates with Pluronic-F68 (9±5% w/w) in a compact stable matricial structure (NP-Chol/0.5-45). In vitro studies highlight the low toxicity and the affinity of NP-Chol/0.5-45 for neuronal cells suggesting their potential applicability in pathologies with a demonstrated alteration of neuronal plasticity and synaptic communication (i.e. Huntington's disease). Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Formulation and Characterization of Acetaminophen Nanoparticles in Orally Disintegrating Films

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    AI-Nemrawi, Nusaiba K.

    The purpose of this study is to prepare acetaminophen loaded nanoparticles to be cast directly, while still in the emulsion form, into Orally Disintegrating Films (ODF). By casting the nanoparticles in the films, we expected to keep the particles in a stable form where the nanoparticles would be away from each other to prevent their aggregation. Once the films are applied on the buccal mucosa, they are supposed to dissolve within seconds, releasing the nanoparticles. Then the nanoparticles could be directly absorbed through the mucosa to the blood stream and deliver acetaminophen there. The oral cavity mucosa is one of the most attractive sites for systemic drug delivery due to its high permeability and blood supply. Furthermore, it is robust and shows short recovery times after stress or damage, and the drug bypasses first pass effect and avoids presystemic elimination in the GI tract. Nanoencapsulation increases drug efficacy, specificity, tolerability and therapeutic index. These Nanocapsules have several advantages in the protection of premature degradation and interaction with the biological environment, enhancement of absorption into a selected tissue, bioavailability, retention time and improvement of intracellular penetration. The most important characteristics of nanoparticles are their size, encapsulation efficiency (EE), zeta potential (surface charge), and the drug release profiles. Unfortunately, nanoparticles tend to precipitate or aggregate into larger particles within a short time after preparation or during storage. Some solutions for this problem were mentioned in literature including lyophilization and spray drying. These methods are usually expensive and give partial solutions that might have secondary problems; such as low re-dispersion efficacy of the lyophilized NPs. Furthermore, most of the formulations of NPs are invasive or topical. Few formulas are available to be given orally. Fast disintegrating films (ODFs) are rapidly gaining interest

  12. Annotating the structure and components of a nanoparticle formulation using computable string expressions.

    Science.gov (United States)

    Thomas, Dennis G; Chikkagoudar, Satish; Chappell, Alan R; Baker, Nathan A

    2012-12-31

    Nanoparticle formulations that are being developed and tested for various medical applications are typically multi-component systems that vary in their structure, chemical composition, and function. It is difficult to compare and understand the differences between the structural and chemical descriptions of hundreds and thousands of nanoparticle formulations found in text documents. We have developed a string nomenclature to create computable string expressions that identify and enumerate the different high-level types of material parts of a nanoparticle formulation and represent the spatial order of their connectivity to each other. The string expressions are intended to be used as IDs, along with terms that describe a nanoparticle formulation and its material parts, in data sharing documents and nanomaterial research databases. The strings can be parsed and represented as a directed acyclic graph. The nodes of the graph can be used to display the string ID, name and other text descriptions of the nanoparticle formulation or its material part, while the edges represent the connectivity between the material parts with respect to the whole nanoparticle formulation. The different patterns in the string expressions can be searched for and used to compare the structure and chemical components of different nanoparticle formulations. The proposed string nomenclature is extensible and can be applied along with ontology terms to annotate the complete description of nanoparticles formulations.

  13. Formulation and In Vitro Characterization of Composite Biodegradable Magnetic Nanoparticles for Magnetically Guided Cell Delivery

    Science.gov (United States)

    Alferiev, Ivan S.; Fishbein, Ilia; Tengood, Jillian E.; Folchman-Wagner, Zoë; Forbes, Scott P.; Levy, Robert J.

    2012-01-01

    Purpose Cells modified with magnetically responsive nanoparticles (MNP) can provide the basis for novel targeted therapeutic strategies. However, improvements are required in the MNP design and cell treatment protocols to provide adequate magnetic properties in balance with acceptable cell viability and function. This study focused on select variables controlling the uptake and cell compatibility of biodegradable polymer-based MNP in cultured endothelial cells. Methods Fluorescent-labeled MNP were formed using magnetite and polylactide as structural components. Their magnetically driven sedimentation and uptake were studied fluorimetrically relative to cell viability in comparison to non-magnetic control conditions. The utility of surface-activated MNP forming affinity complexes with replication-deficient adenovirus (Ad) for transduction achieved concomitantly with magnetic cell loading was examined using the green fluorescent protein reporter. Results A high-gradient magnetic field was essential for sedimentation and cell binding of albumin-stabilized MNP, the latter being rate-limiting in the MNP loading process. Cell loading up to 160 pg iron oxide per cell was achievable with cell viability >90%. Magnetically driven uptake of MNP-Ad complexes can provide high levels of transgene expression potentially useful for a combined cell/gene therapy. Conclusions Magnetically responsive endothelial cells for targeted delivery applications can be obtained rapidly and efficiently using composite biodegradable MNP. PMID:22274555

  14. Formulation of Diblock Polymeric Nanoparticles through Nanoprecipitation Technique

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    Karve, Shrirang; Werner, Michael E.; Cummings, Natalie D.; Sukumar, Rohit; Wang, Edina C.; Zhang, Ying-Ao; Wang, Andrew Z.

    2011-01-01

    Nanotechnology is a relatively new branch of science that involves harnessing the unique properties of particles that are nanometers in scale (nanoparticles). Nanoparticles can be engineered in a precise fashion where their size, composition and surface chemistry can be carefully controlled. This enables unprecedented freedom to modify some of the fundamental properties of their cargo, such as solubility, diffusivity, biodistribution, release characteristics and immunogenicity. Since their inception, nanoparticles have been utilized in many areas of science and medicine, including drug delivery, imaging, and cell biology1-4. However, it has not been fully utilized outside of "nanotechnology laboratories" due to perceived technical barrier. In this article, we describe a simple method to synthesize a polymer based nanoparticle platform that has a wide range of potential applications. The first step is to synthesize a diblock co-polymer that has both a hydrophobic domain and hydrophilic domain. Using PLGA and PEG as model polymers, we described a conjugation reaction using EDC/NHS chemistry5 (Fig 1). We also discuss the polymer purification process. The synthesized diblock co-polymer can self-assemble into nanoparticles in the nanoprecipitation process through hydrophobic-hydrophilic interactions. The described polymer nanoparticle is very versatile. The hydrophobic core of the nanoparticle can be utilized to carry poorly soluble drugs for drug delivery experiments6. Furthermore, the nanoparticles can overcome the problem of toxic solvents for poorly soluble molecular biology reagents, such as wortmannin, which requires a solvent like DMSO. However, DMSO can be toxic to cells and interfere with the experiment. These poorly soluble drugs and reagents can be effectively delivered using polymer nanoparticles with minimal toxicity. Polymer nanoparticles can also be loaded with fluorescent dye and utilized for intracellular trafficking studies. Lastly, these polymer

  15. Development of a Parenteral Formulation of NTS-Polyplex Nanoparticles for Clinical Purpose

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    María E. Aranda-Barradas

    2018-01-01

    Full Text Available Neurotensin (NTS-polyplex is a nanoparticle system for targeted gene delivery that holds great promise for treatment of Parkinson’s disease and various types of cancer. However, the high instability in aqueous suspension of NTS-polyplex nanoparticles is a major limitation for their widespread clinical use. To overcome this obstacle, we developed a clinical formulation and a lyophilization process for NTS-polyplex nanoparticles. The reconstituted samples were compared with fresh preparations by using transmission electron microscopy, dynamic light scattering, electrophoretic mobility, circular dichroism and transfection assays in vitro and in vivo. Our formulation was able to confer lyoprotection and stability to these nanoparticles. In addition, transmission electron microscopy (TEM and size exclusion-high performance liquid chromatography (SEC-HPLC using a radioactive tag revealed that the interaction of reconstituted nanoparticles with fetal bovine or human serum did not alter their biophysical features. Furthermore, the formulation and the lyophilization procedure guaranteed functional NTS-polyplex nanoparticles for at least six months of storage at 25 °C and 60% relative humidity. Our results offer a pharmaceutical guide for formulation and long-term storage of NTS-polyplex nanoparticles that could be applied to other polyplexes.

  16. Complexity of intravenous iron nanoparticle formulations: implications for bioequivalence evaluation.

    Science.gov (United States)

    Pai, Amy Barton

    2017-11-01

    Intravenous iron formulations are a class of complex drugs that are commonly used to treat a wide variety of disease states associated with iron deficiency and anemia. Venofer® (iron-sucrose) is one of the most frequently used formulations, with more than 90% of dialysis patients in the United States receiving this formulation. Emerging data from global markets outside the United States, where many iron-sucrose similars or copies are available, have shown that these formulations may have safety and efficacy profiles that differ from the reference listed drug. This may be attributable to uncharacterized differences in physicochemical characteristics and/or differences in labile iron release. As bioequivalence evaluation guidance evolves, clinicians should be educated on these potential clinical issues before a switch to the generic formulation is made in the clinical setting. © 2017 New York Academy of Sciences.

  17. [Development of Inhalable Dry Powder Formulations Loaded with Nanoparticles Maintaining Their Original Physical Properties and Functions].

    Science.gov (United States)

    Okuda, Tomoyuki

    2017-01-01

     Functional nanoparticles, such as liposomes and polymeric micelles, are attractive drug delivery systems for solubilization, stabilization, sustained release, prolonged tissue retention, and tissue targeting of various encapsulated drugs. For their clinical application in therapy for pulmonary diseases, the development of dry powder inhalation (DPI) formulations is considered practical due to such advantages as: (1) it is noninvasive and can be directly delivered into the lungs; (2) there are few biocomponents in the lungs that interact with nanoparticles; and (3) it shows high storage stability in the solid state against aggregation or precipitation of nanoparticles in water. However, in order to produce effective nanoparticle-loaded dry powders for inhalation, it is essential to pursue an innovative and comprehensive formulation strategy in relation to composition and powderization which can achieve (1) the particle design of dry powders with physical properties suitable for pulmonary delivery through inhalation, and (2) the effective reconstitution of nanoparticles that will maintain their original physical properties and functions after dissolution of the powders. Spray-freeze drying (SFD) is a relatively new powderization technique combining atomization and lyophilization, which can easily produce highly porous dry powders from an aqueous sample solution. Previously, we advanced the optimization of components and process conditions for the production of SFD powders suitable to DPI application. This review describes our recent results in the development of novel DPI formulations effectively loaded with various nanoparticles (electrostatic nanocomplexes for gene therapy, liposomes, and self-assembled lipid nanoparticles), based on SFD.

  18. Formulation and characterization of clozapine and risperidone co-entrapped spray-dried PLGA nanoparticles.

    Science.gov (United States)

    Panda, Apoorva; Meena, Jairam; Katara, Rajesh; Majumdar, Dipak K

    2016-01-01

    In the current study, polylactide-co-glycolide (PLGA) nanoparticles entrapping both clozapine (CLZ) and risperidone (RIS) were formulated by spray-drying using Buchi Nano Spray Dryer B-90 (Flawil, Switzerland). Parameters such as inlet temperature, spray mesh diameter, sample flow rate, spray rate and applied pressure were optimized to produce nanoparticles having desired release profile using both low- and high-molecular weight PLGA polymer. Smallest size nanoparticle of size around 248 nm could be prepared using a 4.0 μm mesh diameter with low-molecular weight polymer. The load of CLZ and RIS was 126.3 and 58.2 μg/mg of polymer particles, respectively. Entrapment efficiency of drugs in PLGA nanoparticles was 94.74% for CLZ and 93.12% for RIS. Both the drugs released continuously from the nanoparticle formulations. PLGA nanoparticles formulated using low-molecular weight polymer released around 80% of the entrapped drug over 10 days of time. Nature of drug inside polymer particles was amorphous, and there was no chemical interaction of CLZ and RIS with polymer. Polymeric nanoparticles were found to be non-toxic in nature using PC12 cell line. This nanospray drying process proved to be suitable for developing polymeric nanoformulation delivering dual drugs for the treatment of Schizophrenia.

  19. Formulation and optimization of solid lipid nanoparticle formulation for pulmonary delivery of budesonide using Taguchi and Box-Behnken design.

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    Emami, J; Mohiti, H; Hamishehkar, H; Varshosaz, J

    2015-01-01

    Budesonide is a potent non-halogenated corticosteroid with high anti-inflammatory effects. The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. The aim of the present study was to develop, characterize and optimize a solid lipid nanoparticle system to deliver budesonide to the lungs. Budesonide-loaded solid lipid nanoparticles were prepared by the emulsification-solvent diffusion method. The impact of various processing variables including surfactant type and concentration, lipid content organic and aqueous volume, and sonication time were assessed on the particle size, zeta potential, entrapment efficiency, loading percent and mean dissolution time. Taguchi design with 12 formulations along with Box-Behnken design with 17 formulations was developed. The impact of each factor upon the eventual responses was evaluated, and the optimized formulation was finally selected. The size and morphology of the prepared nanoparticles were studied using scanning electron microscope. Based on the optimization made by Design Expert 7(®) software, a formulation made of glycerol monostearate, 1.2 % polyvinyl alcohol (PVA), weight ratio of lipid/drug of 10 and sonication time of 90 s was selected. Particle size, zeta potential, entrapment efficiency, loading percent, and mean dissolution time of adopted formulation were predicted and confirmed to be 218.2 ± 6.6 nm, -26.7 ± 1.9 mV, 92.5 ± 0.52 %, 5.8 ± 0.3 %, and 10.4 ± 0.29 h, respectively. Since the preparation and evaluation of the selected formulation within the laboratory yielded acceptable results with low error percent, the modeling and optimization was justified. The optimized formulation co-spray dried with lactose (hybrid microparticles) displayed desirable fine particle fraction, mass median aerodynamic diameter (MMAD), and geometric standard deviation of 49.5%, 2.06 μm, and 2.98 μm; respectively. Our results provide fundamental data for the

  20. Formulation and Characterization of Pyrazinamide Polymeric Nanoparticles for Pulmonary Tuberculosis: Efficiency for Alveolar Macrophage Targeting

    OpenAIRE

    Varma, J. N. Ravi; Kumar, T. Santosh; Prasanthi, B.; Ratna, J. Vijaya

    2015-01-01

    Pyrazinamide, a highly specific agent against Mycobacterium tuberculosis is used as first-line drug to treat tuberculosis. The current work aims to formulate polymeric nanoparticles based drug delivery system to sustain the release profile and reduce the dosing frequency of pyrazinamide. Further aim was to target the macrophages within body fluid. These polymeric nanoparticles were prepared by simultaneous double-emulsion (W/O/W) solvent evaporation/diffusion technique. The prepared dispersio...

  1. Early development drug formulation on a chip: fabrication of nanoparticles using a microfluidic spray dryer.

    Science.gov (United States)

    Thiele, Julian; Windbergs, Maike; Abate, Adam R; Trebbin, Martin; Shum, Ho Cheung; Förster, Stephan; Weitz, David A

    2011-07-21

    Early development drug formulation is exacerbated by increasingly poor bioavailability of potential candidates. Prevention of attrition due to formulation problems necessitates physicochemical analysis and formulation studies at a very early stage during development, where the availability of a new substance is limited to small quantities, thus impeding extensive experiments. Miniaturization of common formulation processes is a strategy to overcome those limitations. We present a versatile technique for fabricating drug nanoformulations using a microfluidic spray dryer. Nanoparticles are formed by evaporative precipitation of the drug-loaded spray in air at room temperature. Using danazol as a model drug, amorphous nanoparticles of 20-60 nm in diameter are prepared with a narrow size distribution. We design the device with a geometry that allows the injection of two separate solvent streams, thus enabling co-spray drying of two substances for the production of drug co-precipitates with tailor-made composition for optimization of therapeutic efficiency.

  2. Effect of formulation variables on preparation of celecoxib loaded polylactide-co-glycolide nanoparticles.

    Directory of Open Access Journals (Sweden)

    Dustin L Cooper

    Full Text Available Polymer based nanoparticle formulations have been shown to increase drug bioavailability and/or reduce drug adverse effects. Nonsteroidal anti-inflammatory drugs (e.g. celecoxib reduce prostaglandin synthesis and cause side effects such as gastrointestinal and renal complications. The aim of this study was to formulate celecoxib entrapped poly lactide-co-glycolide based nanoparticles through a solvent evaporation process using didodecyldimethylammonium bromide or poly vinyl alcohol as stabilizer. Nanoparticles were characterized for zeta potential, particle size, entrapment efficiency, and morphology. Effects of stabilizer concentration (0.1, 0.25, 0.5, and 1% w/v, drug amount (5, 10, 15, and 20 mg, and emulsifier (lecithin on nanoparticle characterization were examined for formula optimization. The use of 0.1, 0.25, and 0.5% w/v didodecyldimethylammonium bromide resulted in a more than 5-fold increase in zeta potential and a more than 1.5-fold increase in entrapment efficiency with a reduction in particle size over 35%, when compared to stabilizer free formulation. Nanoparticle formulations were also highly influenced by emulsifier and drug amount. Using 0.25% w/v didodecyldimethylammonium bromide NP formulations, peak zeta potential was achieved using 15 mg celecoxib with emulsifier (17.15±0.36 mV and 20 mg celecoxib without emulsifier (25.00±0.18 mV. Peak NP size reduction and entrapment efficiency was achieved using 5 mg celecoxib formulations with (70.87±1.24 nm and 95.55±0.66%, respectively and without (92.97±0.51 nm and 95.93±0.27%, respectively emulsifier. In conclusion, formulations using 5 mg celecoxib with 0.25% w/v didodecyldimethylammonium bromide concentrations produced nanoparticles exhibiting enhanced size reduction and entrapment efficiency. Furthermore, emulsifier free formulations demonstrated improved zeta potential when compared to formulations containing emulsifier (p<0.01. Therefore, our results suggest the use of

  3. Cubic phase nanoparticles for sustained release of ibuprofen: formulation, characterization, and enhanced bioavailability study

    Science.gov (United States)

    Dian, Linghui; Yang, Zhiwen; Li, Feng; Wang, Zhouhua; Pan, Xin; Peng, Xinsheng; Huang, Xintian; Guo, Zhefei; Quan, Guilan; Shi, Xuan; Chen, Bao; Li, Ge; Wu, Chuanbin

    2013-01-01

    In order to improve the oral bioavailability of ibuprofen, ibuprofen-loaded cubic nanoparticles were prepared as a delivery system for aqueous formulations. The cubic inner structure was verified by cryogenic transmission electron microscopy. With an encapsulation efficiency greater than 85%, the ibuprofen-loaded cubic nanoparticles had a narrow size distribution around a mean size of 238 nm. Differential scanning calorimetry and X-ray diffraction determined that ibuprofen was in an amorphous and molecular form within the lipid matrix. The in vitro release of ibuprofen from cubic nanoparticles was greater than 80% at 24 hours, showing sustained characteristics. The pharmacokinetic study in beagle dogs showed improved absorption of ibuprofen from cubic nanoparticles compared to that of pure ibuprofen, with evidence of a longer half-life and a relative oral bioavailability of 222% (P ibuprofen-loaded cubic nanoparticles provide a promising carrier candidate with an efficient drug delivery for therapeutic treatment. PMID:23468008

  4. Design of Novel Ophthalmic Formulation Containing Drug Nanoparticles and Its Usefulness as Anti-glaucoma Drugs.

    Science.gov (United States)

    Nagai, Noriaki

    2016-01-01

    The ophthalmic application of drugs is the primary route of administration for the therapy of glaucoma; however, in traditional formulations, only small amounts of the administered drug penetrate the cornea to reach the desired intraocular tissue due to corneal barriers. Recently, nanoparticulate drug delivery is expected as a technology to overcome the difficulties in delivering drugs across biological barriers (improvement of bioavailability). In this study, we attempted to establish a new method for preparing solid drug nanoparticles by using a bead mill and various additives, and succeeded in preparing a high quality dispersion containing drug nanoparticles. For a more concrete example, a mean particle size of disulfiram (DSF) treated with bead mill is 183 nm. The corneal penetration and corneal residence time of DSF from the ophthalmic dispersion containing DSF nanoparticles were significantly higher than those from a 2-hydroxypropyl-β-cyclodextrin solution containing DSF (DSF solution). It is known that the administration of DSF has intraocular pressure (IOP)-reducing effects. The IOP-reducing effects of the ophthalmic dispersion containing DSF nanoparticles were significantly greater than those of the DSF solution in rabbits (the IOP was enhanced by placing the rabbits in a dark room for 5 h). In addition, the ophthalmic dispersion containing DSF nanoparticles is better tolerated by corneal epithelial cells than DSF solution. It is possible that dispersions containing DSF nanoparticles provide new possibilities for effectively treating glaucoma, and that ocular drug delivery systems using drug nanoparticles may expand their usage for therapy in the ophthalmologic field.

  5. Formulation and investigation of 5-FU nanoparticles with factorial design-based studies.

    Science.gov (United States)

    Bozkir, Asuman; Saka, Ongun Mehmet

    2005-10-01

    This study describes an orthogonal experimental design to optimize the formulation of 5-fluorouracil (5-FU) loaded poly D,L (lactide-co-glycolide) (PLGA) nanoparticles (5FU-NP) by a nanoprecipitation-solvent displacement technique. The type of surfactant, amount of acetone and molecular weight of the polymer with three levels of each factor were selected and arranged in an L18(3(5)) orthogonal experimental table. From the statistical analysis of the data polynominal equations were generated. Optimized formulations have the particle size ranging from 160 to 250 nm. Smallest nanoparticles (161+/-1.22 nm) were obtained using Resomer PLGA 755 and pluronic F-68 with 10 ml acetone amount. Under these conditions the 5-FU entrapment percentage was maximum 78.30%, suggesting 5-FU might be entrapped and adsorbed on the nanoparticle surface. In vitro release of three formulations with maximum drug entrapment efficiency and minimum particle size, were also investigated by release kinetics. According to the determined coefficients, release data fit to Higuchi's diffusion kinetics. The in vitro release of 5FU-NP in phosphate buffered saline (PBS, pH 7.4) is suggested to be controlled by a combination of diffusion with slow and gradual erosion of the particles. Also, the antimicrobial activity was observed even on the end of seventh day with all formulations.

  6. Lipid nanoparticles for transdermal delivery of flurbiprofen: formulation, in vitro, ex vivo and in vivo studies

    Directory of Open Access Journals (Sweden)

    Venkateswarlu Vobalaboina

    2009-02-01

    Full Text Available Abstract The aim of the study is to prepare aqueous dispersions of lipid nanoparticles – flurbiprofen solid lipid nanoparticles (FLUSLN and flurbiprofen nanostructured lipid carriers (FLUNLC by hot homogenization followed by sonication technique and then incorporated into the freshly prepared hydrogels for transdermal delivery. They are characterized for particle size, for all the formulations, more than 50% of the particles were below 300 nm after 90 days of storage at RT. DSC analyses were performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by TEM which revealed fairly spherical shape of the formulations. Further they were evaluated for in vitro drug release characteristics, rheological behaviour, pharmacokinetic and pharmacodynamic studies. The pharmacokinetics of flurbiprofen in rats following application of SLN gel (A1 and NLC gel (B1 for 24 h were evaluated. The Cmax of the B1 formulation was 38.67 ± 2.77 μg/ml, which was significantly higher than the A1 formulation (Cmax = 21.79 ± 2.96 μg/ml. The Cmax and AUC of the B1 formulation were 1.8 and 2.5 times higher than the A1 gel formulation respectively. The bioavailability of flurbiprofen with reference to oral administration was found to increase by 4.4 times when gel formulations were applied. Anti-inflammatory effect in the Carrageenan-induced paw edema in rat was significantly higher for B1 and A1 formulation than the orally administered flurbiprofen. Both the SLN and NLC dispersions and gels enriched with SLN and NLC possessed a sustained drug release over period of 24 h but the sustained effect was more pronounced with the SLN and NLC gel

  7. Improved Poly (D,L-lactide) nanoparticles-based formulation for hair follicle targeting.

    Science.gov (United States)

    Fernandes, B; Silva, R; Ribeiro, A; Matamá, T; Gomes, A C; Cavaco-Paulo, A M

    2015-06-01

    Hair follicles are widely recognized as the preferential target and site of accumulation for nanoparticles after topical application. This feature is of particular importance for hair cosmetics, having the potential to refine the treatment of several hair follicle-related disorders. The aim of this work was to improve the preparation of Poly (D,L-lactide) (PLA) nanoparticles for in vivo follicular target and drug delivery. Envisaging a future industrial scale-up of the process, nanoprecipitation method was used to prepare PLA nanoparticles: the effect of several processing parameters on their properties was examined and the yield of nanoparticles formation determined. Encapsulation efficiencies and in vitro release profiles of lipophilic and hydrophilic model compounds were also assessed. In vitro cytotoxicity and ex vivo penetration studies were performed on a reference skin cell line (NCTC2455, human skin keratinocytes) and porcine skin, respectively. Using acetone : ethanol (50 : 50, v/v) as the solvent phase, 0.6% (w/w) of Pluronic(®) F68 as a surfactant agent and agitation to mix the solvent and non-solvent phases, a monodispersed population of non-cytotoxic spherical nanoparticles of approximately 150 nm was obtained. The yield of nanoparticles for this formulation was roughly 90%. After encapsulation of model compounds, no significant changes were found in the properties of particles and the entrapment efficiencies were above 80%. The release kinetics of dyes from PLA nanoparticles indicate an anomalous transport mechanism (diffusion and polymer degradation) for Nile Red (lipophilic) and a Fickian diffusion of first order for fluorescein 5(6)-isothiocyanate (hydrophilic). Ex vivo skin penetration studies confirmed the presence of nanoparticles along the entire follicular ducts. The optimized method allows the preparation of ideal PLA nanoparticles-based formulations for hair follicle targeting. PLA nanoparticles can effectively transport and release

  8. Formulation effects on the release of silica dioxide nanoparticles from paint debris to water.

    Science.gov (United States)

    Zuin, Stefano; Massari, Andrea; Ferrari, Arlen; Golanski, Luana

    2014-04-01

    Waterborne paints with integrated nanoparticles have been recently introduced into the market as nanoparticles offer improved or novel functionalities to paints. However, the release of nanoparticles during the life cycle of nano-enhanced paint has only been studied to a very limited extent. The paint composition could determine in what quantities and forms the nanoparticles are released. In this work, paint formulations containing the same amount of silicon dioxide (SiO2) nanoparticles but differing in the pigment volume concentration (PVC) and in amount and type of binder and pigment, were studied through leaching test to investigate the influence of these parameters on release of Si from paint. The results indicate greater release of Si, about 1.7 wt.% of the SiO2 nanoparticles in the paint, for paint formulated with higher PVC value (63%), suggesting that the PVC is a crucial factor for release of SiO2 nanoparticles from paints. This hypothesis was also based on the fact that agglomerates of SiO2 nanoparticles were only found in leachates from paint with higher PVC. A paint sample with the higher amount of binder and less calcite filler exhibited a lower release of Si among the paints with a low PVC value (35%), and no SiO2 particles were detected in leachates collected from this paint. This could be due to the fact that a high portion of binder forms a suitable matrix to hold the SiO2 ENPs in paint. The paint sample in which the amount of calcite was partially substituted with TiO2 pigment did not show an important reduction on Si release. Our work suggests that paint debris containing SiO2 nanoparticles may release a limited amount of Si into the environment, and that by adjusting the properties of the binder in combination with common pigments it is possible to reduce the release of SiO2 nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Polymer Stabilized Nanosuspensions Formed via Flash Nanoprecipitation: Nanoparticle Formation, Formulation, and Stability

    Science.gov (United States)

    Zhu, ZhengXi

    Nanoparticles loaded with hydrophobic components (e.g., active pharmaceutical ingredients, medical diagnostic agents, nutritional or personal care chemicals, catalysts, dyes/pigments, and substances with exceptional magnetic/optical/electronic/thermal properties) have tremendous industrial applications. The common desire is to efficiently generate nanoparticles with a desired size, size distribution, and size stability. Recently, Flash NanoPrecipition (FNP) technique with a fast, continuous, and easily scalable process has been developed to efficiently generate hydrophobe-loaded nanoparticles. This dissertation extended this technique, optimized process conditions and material formulations, and gave new insights into the mechanism and kinetics of nanoparticle formation. This dissertation demonstrated successful generation of spherical beta-carotene nanoparticles with an average diameter of 50--100 nm (90 wt% nanoparticles below 200 nm), good size stability (maintained an average diameter below 200 nm for at least one week in saline), and much higher loading (80--90 wt%) than traditional carriers, such as micelles and polymersomes (typically FNP were proposed. To optimize the material formulations, either polyelectrolytes (i.e., epsilon-polylysine, branched and linear poly(ethylene imine), and chitosan) or amphiphilic diblock copolymers (i.e., polystyrene-b-poly(ethylene glycol) (PS-b-PEG), polycarprolactone-b-poly(ethylene glycol) (PCL-b-PEG), poly(lactic acid)-b-poly(ethylene glycol) (PLA-b-PEG), and poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG)) were selectively screened to study the nanoparticle size, distribution, and stability. The effect of the molecular weight of the polymers and pH were also studied. Chitosan and PLGA-b-PEG best stabilized the beta-carotene nanoparticles. Solubility of the hydrophobic drug solute in the aqueous mixture was considered to dominate the nanoparticle stability (i.e., size and morphology) in terms of Ostwald

  10. Preparation of finasteride capsules-loaded drug nanoparticles: formulation, optimization, in vitro, and pharmacokinetic evaluation

    Directory of Open Access Journals (Sweden)

    Ahmed TA

    2016-02-01

    Full Text Available Tarek A Ahmed1,2 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt Abstract: In this study, optimized freeze-dried finasteride nanoparticles (NPs were prepared from drug nanosuspension formulation that was developed using the bottom–up technique. The effects of four formulation and processing variables that affect the particle size and solubility enhancement of the NPs were explored using the response surface optimization design. The optimized formulation was morphologically characterized using transmission electron microscopy (TEM. Physicochemical interaction among the studied components was investigated. Crystalline change was investigated using X-ray powder diffraction (XRPD. Crystal growth of the freeze-dried NPs was compared to the corresponding aqueous drug nanosuspension. Freeze-dried NPs formulation was subsequently loaded into hard gelatin capsules that were examined for in vitro dissolution and pharmacokinetic behavior. Results revealed that in most of the studied variables, some of the quadratic and interaction effects had a significant effect on the studied responses. TEM image illustrated homogeneity and shape of the prepared NPs. No interaction among components was noticed. XRPD confirmed crystalline state change in the optimized NPs. An enhancement in the dissolution rate of more than 2.5 times from capsules filled with optimum drug NPs, when compared to capsules filled with pure drug, was obtained. Crystal growth, due to Ostwald ripening phenomenon and positive Gibbs free energy, was reduced following lyophilization of the nanosuspension formulation. Pharmacokinetic parameters from drug NPs were superior to that of pure drug and drug microparticles. In conclusion, freeze-dried NPs based on drug nanosuspension formulation is a successful

  11. Shielding the cationic charge of nanoparticle-formulated dermal DNA vaccines is essential for antigen expression and immunogenicity

    NARCIS (Netherlands)

    Berg, J.H. van den; Oosterhuis, K.; Hennink, W.E.; Storm, G.; Aa, L.J.; Engbersen, J.F.J.; Haanen, J.B.A.G.; Beijnen, J.H.; Schumacher, T.N.; Nuijen, B.

    2010-01-01

    Nanoparticle-formulated DNA vaccines hold promise for the design of in vivo vaccination platforms that target defined cell types in human skin. A variety of DNA formulations, mainly based on cationic liposomes or polymers, has been investigated to improve transfection efficiency in in vitro

  12. Shielding the cationic charge of nanoparticle-formulated dermal DNA vaccines is essential for antigen expression and immunogenicity

    NARCIS (Netherlands)

    van den Berg, Joost H.; Oosterhuis, Koen; Hennink, Wim E.; Storm, Gert; Storm, Gerrit; van der Aa, L.J.; Engbersen, Johannes F.J.; Haanen, John B.A.G.; Beijnen, Jos H.; Schumacher, Ton N.; Nuijen, Bastiaan

    2010-01-01

    Nanoparticle-formulated DNA vaccines hold promise for the design of in vivo vaccination platforms that target defined cell types in human skin. A variety of DNA formulations, mainly based on cationic liposomes or polymers, has been investigated to improve transfection efficiency in in vitro assays.

  13. Formulation of novel lipid-coated magnetic nanoparticles as the probe for in vivo imaging

    Directory of Open Access Journals (Sweden)

    Mou Chung-Yuan

    2009-09-01

    Full Text Available Abstract Background Application of superparamagnetic iron oxide nanoparticles (SPIOs as the contrast agent has improved the quality of magnetic resonance (MR imaging. Low efficiency of loading the commercially available iron oxide nanoparticles into cells and the cytotoxicity of previously formulated complexes limit their usage as the image probe. Here, we formulated new cationic lipid nanoparticles containing SPIOs feasible for in vivo imaging. Methods Hydrophobic SPIOs were incorporated into cationic lipid 1,2-dioleoyl-3-(trimethylammonium propane (DOTAP and polyethylene-glycol-2000-1,2-distearyl-3-sn-phosphatidylethanolamine (PEG-DSPE based micelles by self-assembly procedure to form lipid-coated SPIOs (L-SPIOs. Trace amount of Rhodamine-dioleoyl-phosphatidylethanolamine (Rhodamine-DOPE was added as a fluorescent indicator. Particle size and zeta potential of L-SPIOs were determined by Dynamic Light Scattering (DLS and Laser Doppler Velocimetry (LDV, respectively. HeLa, PC-3 and Neuro-2a cells were tested for loading efficiency and cytotoxicity of L-SPIOs using fluorescent microscopy, Prussian blue staining and flow cytometry. L-SPIO-loaded CT-26 cells were tested for in vivo MR imaging. Results The novel formulation generates L-SPIOs particle with the average size of 46 nm. We showed efficient cellular uptake of these L-SPIOs with cationic surface charge into HeLa, PC-3 and Neuro-2a cells. The L-SPIO-loaded cells exhibited similar growth potential as compared to unloaded cells, and could be sorted by a magnet stand over ten-day duration. Furthermore, when SPIO-loaded CT-26 tumor cells were injected into Balb/c mice, the growth status of these tumor cells could be monitored using optical and MR images. Conclusion We have developed a novel cationic lipid-based nanoparticle of SPIOs with high loading efficiency, low cytotoxicity and long-term imaging signals. The results suggested these newly formulated non-toxic lipid-coated magnetic

  14. Current Challenges and Future of Lipid nanoparticles formulations for topical drug application to oral mucosa, skin, and eye.

    Science.gov (United States)

    Guilherme, Viviane A; Ribeiro, Ligia N M; Tofoli, Giovana Radomille; Franz-Montan, Michelle; de Paula, Eneida; de Jesus, Marcelo Bispo

    2017-11-21

    Topical drug administration offers an attractive route with minimal invasiveness. It also avoids limitations of intravenous administration such as the first pass metabolism and presystemic elimination within the gastrointestinal tract. Furthermore, topical drug administration is safe, have few side effects, is easy to apply, and offers a fast onset of action. However, the development of effective topical formulations still represents a challenge for the desired effect to be reached, locally or systemically. Solid lipid nanoparticles and nanostructured lipid carriers are particular candidates to overcome the problem of topical drug administration. The nanometric particle size of lipid nanoparticles favors the physical adhesion to the skin or mucosal, what can also be attained with the formation of hybrid (nanoparticles/polymer) systems. In this review, we discuss the major challenges for lipid nanoparticles formulations for topical application to oral mucosa, skin, and eye, highlighting the strategies to improve the performance of lipid nanoparticles for topical applications. Next, we critically analyzed the in vitro and in vivo approaches used to evaluate lipid nanoparticles performance and toxicity. We addressed some major drawbacks related to lipid nanoparticle topical formulations and concluded the key points that have to be overcome to help them to reach the market in topical formulations to oral mucosa, skin and eye. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms.

    Science.gov (United States)

    Ong, Teik Hwa; Chitra, Ebenezer; Ramamurthy, Srinivasan; Siddalingam, Rajinikanth Paruvathanahalli; Yuen, Kah Hay; Ambu, Stephen Periathamby; Davamani, Fabian

    2017-01-01

    Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC) analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 μg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 μg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections.

  16. Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms.

    Directory of Open Access Journals (Sweden)

    Teik Hwa Ong

    Full Text Available Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 μg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 μg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections.

  17. Preparation of finasteride capsules-loaded drug nanoparticles: formulation, optimization, in vitro, and pharmacokinetic evaluation.

    Science.gov (United States)

    Ahmed, Tarek A

    2016-01-01

    In this study, optimized freeze-dried finasteride nanoparticles (NPs) were prepared from drug nanosuspension formulation that was developed using the bottom-up technique. The effects of four formulation and processing variables that affect the particle size and solubility enhancement of the NPs were explored using the response surface optimization design. The optimized formulation was morphologically characterized using transmission electron microscopy (TEM). Physicochemical interaction among the studied components was investigated. Crystalline change was investigated using X-ray powder diffraction (XRPD). Crystal growth of the freeze-dried NPs was compared to the corresponding aqueous drug nanosuspension. Freeze-dried NPs formulation was subsequently loaded into hard gelatin capsules that were examined for in vitro dissolution and pharmacokinetic behavior. Results revealed that in most of the studied variables, some of the quadratic and interaction effects had a significant effect on the studied responses. TEM image illustrated homogeneity and shape of the prepared NPs. No interaction among components was noticed. XRPD confirmed crystalline state change in the optimized NPs. An enhancement in the dissolution rate of more than 2.5 times from capsules filled with optimum drug NPs, when compared to capsules filled with pure drug, was obtained. Crystal growth, due to Ostwald ripening phenomenon and positive Gibbs free energy, was reduced following lyophilization of the nanosuspension formulation. Pharmacokinetic parameters from drug NPs were superior to that of pure drug and drug microparticles. In conclusion, freeze-dried NPs based on drug nanosuspension formulation is a successful technique in enhancing stability, solubility, and in vitro dissolution of poorly water-soluble drugs with possible impact on the drug bioavailability.

  18. Polymeric Nanoparticles as a Metolachlor Carrier: Water-Based Formulation for Hydrophobic Pesticides and Absorption by Plants.

    Science.gov (United States)

    Tong, Yujia; Wu, Yan; Zhao, Caiyan; Xu, Yong; Lu, Jianqing; Xiang, Sheng; Zong, Fulin; Wu, Xuemin

    2017-08-30

    Pesticide formulation is highly desirable for effective utilization of pesticide and environmental pollution reduction. Studies of pesticide delivery system such as microcapsules are developing prosperously. In this work, we chose polymeric nanoparticles as a pesticide delivery system and metolachlor was used as a hydrophobic pesticide model to study water-based mPEG-PLGA nanoparticle formulation. Preparation, characterization results showed that the resulting nanoparticles enhanced "water solubility" of hydrophobic metolachlor and contained no organic solvent or surfactant, which represent one of the most important sources of pesticide pollution. After the release study, absorption of Cy5-labeled nanoparticles into rice roots suggested a possible transmitting pathway of this metolachlor formulation and increased utilization of metolachlor. Furthermore, the bioassay test demonstrated that this nanoparticle showed higher effect than non-nano forms under relatively low concentrations on Oryza sativa, Digitaria sanguinalis. In addition, a simple cytotoxicity test involving metolachlor and metolachlor-loaded nanoparticles was performed, indicating toxicity reduction of the latter to the preosteoblast cell line. All of these results showed that those polymeric nanoparticles could serve as a pesticide carrier with lower environmental impact, comparable effect, and effective delivery.

  19. Formulation and optimization of itraconazole polymeric lipid hybrid nanoparticles (Lipomer) using Box Behnken design.

    Science.gov (United States)

    Gajra, Balaram; Dalwadi, Chintan; Patel, Ravi

    2015-01-21

    The objective of the study was to formulate and to investigate the combined influence of 3 independent variables in the optimization of Polymeric lipid hybrid nanoparticles (PLHNs) (Lipomer) containing hydrophobic antifungal drug Itraconazole and to improve intestinal permeability. The Polymeric lipid hybrid nanoparticle formulation was prepared by the emulsification solvent evaporation method and 3 factor 3 level Box Behnken statistical design was used to optimize and derive a second order polynomial equation and construct contour plots to predict responses. Biodegradable Polycaprolactone, soya lecithin and Poly vinyl alcohol were used to prepare PLHNs. The independent variables selected were lipid to polymer ratio (X1) Concentration of surfactant (X2) Concentration of the drug (X3). The Box-Behnken design demonstrated the role of the derived equation and contour plots in predicting the values of dependent variables for the preparation and optimization of Itraconazole PLHNs. Itraconazole PLHNs revealed nano size (210 ± 1.8 nm) with an entrapment efficiency of 83 ± 0.6% and negative zeta potential of -11.7 mV and also enhance the permeability of itraconazole as the permeability coefficient (Papp) and the absorption enhancement ratio was higher. The tunable particle size, surface charge, and favourable encapsulation efficiency with a sustained drug release profile of PLHNs suggesting that it could be promising system envisioned to increase the bioavailability by improving intestinal permeability through lymphatic uptake, M cell of payer's patch or paracellular pathway which was proven by confocal microscopy.

  20. Formulation and in vitro interaction of rhodamine-B loaded PLGA nanoparticles with cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Antranik Jonderian

    2016-12-01

    Full Text Available This study aims to characterize rhodamine B (Rh B loaded poly(D,L-lactide-co-glycolide (PLGA nanoparticles (NPs and their interactions with cardiac myocytes. PLGA NPs were formulated using single emulsion solvent evaporation technique. The influence of varying parameters such as the stabilizer concentration, the sonication time, and the organic to aqueous ratio were investigated. The diameter, the dispersity, the encapsulation efficiency and the zeta potential of the optimized nanoparticles were about 184 nm, 0.19, 40% and -21.7 mV respectively. In vitro release showed that 29% of the Rh B was released within the first 8 hours. Scanning electron microscopy (SEM measurements performed on the optimized nanoparticles showed smooth surface and spherical shapes. No significant cytotoxic or apoptotic effects were observed on fetal cardiac myocytes after 24 and 48 hours of exposure with concentrations up to 200 µg/mL. The kinetic of the intracellular uptake was confirmed by confocal microscopy and cells took up PLGA NPs within the first hours. Interestingly, our data show an increase in the nanoparticles’ uptake with time of exposure. Taken together, we demonstrate for the first time that the designed NPs can be used as potential probes for drug delivery in cardiac myocytes.

  1. Topophore C: a liposomal nanoparticle formulation of topotecan for treatment of ovarian cancer.

    Science.gov (United States)

    Patankar, Nilesh A; Waterhouse, Dawn; Strutt, Dita; Anantha, Malathi; Bally, Marcel B

    2013-02-01

    We have recently developed a liposomal nanoparticle (LNP) formulation of irinotecan based on loading method that involves formation of a complex between copper and the water soluble camptothecin. The loading methodology developed for irinotecan was evaluated to develop a LNP topotecan formulation (referred to herein as Topophore C) and test its activity in pre-clinical model of ovarian carcinoma. Topotecan was encapsulated into preformed liposomes containing 300 mM copper sulfate and the divalent metal ionophore A23187. Formulation optimization studies included assessments of loading efficiency, influence of temperature on drug loading and in vitro stability of the resulting formulation. In vivo assessments included drug and liposome pharmacokinetics, drug levels within plasma and the peritoneal cavity following intravenous (i.v.) administration in mice and efficacy studies on ES2 ovarian cancer model. Topotecan loading into liposomes was optimized with encapsulation efficiency of >98 % at a final drug-to-lipid (D/L) mole ratio of 0.1. Higher D/L ratios could be achieved, but the resulting formulations were less stable as judged by in vitro drug release studies. Following Topophore C administration in mice the topotecan plasma half-life and AUC were increased compared to free topotecan by 10-and 22-fold, respectively. Topophore C was 2-to 3-fold more toxic than free topotecan, however showed significantly better anti-tumor activity than free topotecan administered at doses with no observable toxic effects. Topophore C is a therapeutically interesting drug candidate and we are particularly interested in developing its use in combination with liposomal doxorubicin for treatment of platinum refractory ovarian cancer.

  2. Formulation of sunscreens with enhancement sun protection factor response based on solid lipid nanoparticles.

    Science.gov (United States)

    Nesseem, D

    2011-02-01

    Solid lipid nanoparticle (SLN) was regarded as new topical delivery systems for pharmaceutical and cosmetic active ingredients. The purpose of this study is to develop carrier systems for organic and inorganic sunscreens based on a matrix composed of carnauba wax and decyl oleate. Formulae (F1-F7) were prepared using butyl methoxydibenzoylmethane and octyl methoxycinnamate as organic components, and titanium dioxide (TiO(2) ) was used as inorganic component. Both types of sunscreens were incorporated into SLN formulations using classical method of preparation. To evaluate the effect of the pigments on the nanoparticles, particle size was measured using Mastersizer particle size analyser. UV-protection abilities of formulations were investigated by the in vitro sun protection factor test (SPF). Further parameters determined were spreadability as well as viscosity. The rheological behaviour of the formulations was also carried out. From the plot of log of shear stress vs. log of shear rate, the slope of the plot representing flow index and ontology of the y-intercept indicating consistency index was calculated. The formulae showed a flow index of 0.2074-0.4005 indicating pseudoplastic flow behaviour. Significant increases in SPF values up to about 50 were reported after the encapsulation by using organic and inorganic filters in Canada wax and decyl oleate. So, SLN could be appropriate vehicles to carry organic and inorganic sunscreens. The rational combination of cinnamates, titanium dioxide and Zinc oxide has shown a synergistic effect to improve the SPF of cosmetic preparations. © 2010 The Author. Journal compilation. © 2010 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  3. New CeO2 nanoparticles-based topical formulations for the skin protection against organophosphates

    Directory of Open Access Journals (Sweden)

    Arnaud Zenerino

    2015-01-01

    Full Text Available To reinforce skin protection against organophosphates (OPs, the development of new topical skin protectants (TSP has received a great interest. Nanoparticles like cerium dioxide (CeO2 known to adsorb and neutralize OPs are interesting candidates for TSP. However, NPs are difficult to disperse into formulations and they are suspected of toxicological issues. Thus, we want to study: (1 the effect of the addition of CeO2 NPs in formulations for the skin protection (2 the impact of the doping of CeO2 NPs by calcium; (3 the effect of two methods of dispersion of CeO2 NPs: an O/W emulsion or a suspension of a fluorinated thickening polymer (HASE-F grafted with these NPs. As a screening approach we used silicone membranes as a skin equivalent and Franz diffusion cells for permeation tests. The addition of pure CeO2 NPs in both formulations permits the penetration to decrease by a 3–4-fold factor. The O/W emulsion allows is the best approach to obtain a film-forming coating with a good reproducibility of the penetration results; whereas the grafting of NPs to a thickener is the best way to obtain an efficient homogenous suspension of CeO2 NPs with a decreased of toxicological impact but the coating is less film-forming which slightly impacts the reproducibility of the penetration results.

  4. Solid phospholipid nano-particles: investigations into formulation and dissolution properties of griseofulvin.

    Science.gov (United States)

    Brinkmann-Trettenes, Ulla; Bauer-Brandl, Annette

    2014-06-05

    Solid phospholipid (PL) nanoparticles with griseofulvin (GRIS) as a model drug were prepared by co-spray drying. Their dissolution properties were compared with formulations containing the physical blends of the native crystalline drug and excipient materials, and physical blends of the spray dried materials. Co-spray drying was performed from ethanol+water solutions (80+20) using Büchi Nano Spray Dryer B-90. Dissolution profiles in phosphate buffer (PBS), simulated intestinal fluids (fasted state simulated intestinal fluid (FaSSIF)) and pancreatin containing media (PAN) were studied. It was found that the influence of PL on the dissolution profile was affected by both the solid state of the drug formulation and the dissolution medium: the co-SD formulations showed the fastest release in all media. The amount of GRIS dissolved after 5h increases by a factor of 7 for the co SD as compared to physical blend of native materials in PBS, and a factor of 4 in FaSSIF respectively. Surprisingly, in contrast to PBS, dissolution rate in FaSSIF decreased with increasing the PL content. All the pancreatin containing media showed a decrease in dissolution rate and extent independently of the processing methods due to an incompatibility between GRIS and PAN. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Formulation and characterization of solid lipid nanoparticles for an anti-retroviral drug darunavir

    Science.gov (United States)

    Bhalekar, Mangesh; Upadhaya, Prashant; Madgulkar, Ashwini

    2017-02-01

    Darunavir, an anti-HIV drug having poor solubility in aqueous and lipid medium, illustrates degradation above its melting point, i.e. 74 °C, thus, posing a challenge to dosage formulation. Despite, the drug suffers from poor oral bioavailability (37%) owing to less permeability and being poly-glycoprotein and cyp3A metabolism substrate. The study aimed formulating a SLN system to overcome the formulation and bioavailability associated problems of the drug. Based on the drug solubility and stable dispersion findings, lipid and surfactant were chosen and nanoparticles were prepared using hot-homogenization technique. Optimization of variables such as lipid concentration, oil-surfactant and homogenization cycle was carried and their effect on particle size and entrapment efficiency was studied. Freeze-dried SLN further characterized using SEM, DSC and PXRD analysis revealed complete entrapment of the drug and amorphous nature of the SLN. In vitro pH release studies in 0.1 N HCl and 6.8 pH buffer demonstrated 84 and 80% release at the end of 12th h. The apparent permeability of the SLN across rat intestine was found to be 24 × 10-6 at 37 °C at the end of 30 min while at 4 °C the same was found to be 5.6 × 10-6 prompting involvement of endocytic processes in the uptake of SLN. Accelerated stability studies revealed no prominent changes upon storage.

  6. Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles and nanostructured lipid carriers

    Directory of Open Access Journals (Sweden)

    RP Thatipamula

    2011-03-01

    Full Text Available Background and the purpose of the study: Domperidone (DOM is a dopamine- receptor (D2 antagonist, widely used in the treatment of motion-sickness. The pharmacokinetic parameters of DOM make it a suitable candidate for development of Solid Lipid Nanoparticle (SLN and Nanostructured Lipide Carrier (NLC. The purpose of the present investigation was to prepare and evaluate DOM loaded solid lipid nanoparticles (DOM-SLN and DOM loaded nanostructured lipid carriers (DOM-NLC. Methods: DOM loaded SLN and NLC were prepared by hot homogenization followed by ultrasonication technique, using trimyristin as solid lipid, cetyl recinoleate as liquid lipid and a mixture of soy phosphatidylcholine (99% and tween 80 as surfactant. SLN and NLC were characterized for particle size, polydispersity index (PDI, zeta potential and entrapment efficiency. The effects of composition of lipid materials and surfactant mixture on the particle size, PDI, zeta potential, drug entrapment efficiency, and in vitro drug release behavior were investigated. DSC analysis was performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by transmission electron microscopy (TEM. SLN and NLC formulations were subjected to stability study over a period of 40 days. Results: The mean particle size, PDI, zeta potential and entrapment efficiency of optimized SLN (SLN1 and NLC were found to be 30.45 nm, 0.156, 12.40 mV, 87.84 % and 32.23 nm, 0.160, 10.47 mV, 90.49 % respectively. DSC studies revealed that DOM was in an amorphous state and triglycerides were in the β prime form in SLN and NLC. Shape and surface morphology was determined by TEM revealed fairly spherical shape of nanoparticles. In vitro release studies demonstrated that both the SLN and NLC formulations possessed a controlled release over a period of 24 hrs. SLN and NLC formulations were subjected to stability over a period of 40 days. There was no significant (P < 0.05 change

  7. MMB4 DMS nanoparticle suspension formulation with enhanced stability for the treatment of nerve agent intoxication.

    Science.gov (United States)

    Dixon, Hong; Clark, Andrew P-Z; Cabell, Larry A; McDonough, Joe A

    2013-01-01

    Various oximes are currently fielded or under investigation in the United States and other countries as a component of autoinjector emergency treatment systems for organophosphate nerve agent chemical weapons. Bis-pyridinium oximes in general have greater efficacy against a broad spectrum of nerve agents, but they have poor stability due to hydrolytic degradation at elevated temperatures. 1,1'-Methylenebis-4-[(hydroxyimino)methyl]pyridinium dimethanesulfonate (MMB4 DMS) is a leading candidate for next-generation nerve agent treatment systems, because it is more stable than other bis-pyridinium oximes, but it still degrades quickly at temperatures often encountered during storage and field use. The primary goal is to increase the stability and shelf life of MMB4 while maintaining the desirable pharmacokinetic (PK) properties of the aqueous formulation. We have developed a formulation to be used in a phase 1 clinical trial consisting of MMB4 micro/nanoparticles suspended in cottonseed oil, a biocompatible vegetable oil. Through various milling techniques, the average particle size can be controlled from approximately 200 to 6000 nm to produce non-Newtonian formulations that are viscous enough to resist rapid particle sedimentation while remaining injectable at a range of concentrations from 5 to 400 mg/mL. The preliminary accelerated stability test shows that MMB4 in these formulations is stable for at least 2 years at temperatures up to 80°C. Preliminary preclinical in vivo studies have demonstrated that all concentrations and particle sizes have desirable PK properties, including high bioavailability and rapid absorption, which is critical to combat potent and fast-acting nerve agents.

  8. Formulation, Characterization, and in Vivo Evaluation of Celecoxib-PVP Solid Dispersion Nanoparticles Using Supercritical Antisolvent Process

    Directory of Open Access Journals (Sweden)

    Eun-Sol Ha

    2014-12-01

    Full Text Available The aim of this study was to develop celecoxib-polyvinylpyrrolidone (PVP solid dispersion nanoparticles with and without surfactant using the supercritical antisolvent (SAS process. The effect of different surfactants such as gelucire 44/14, poloxamer 188, poloxamer 407, Ryoto sugar ester L1695, and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS on nanoparticle formation and dissolution as well as oral absorption of celecoxib-PVP K30 solid dispersion nanoparticles was investigated. Spherical celecoxib solid dispersion nanoparticles less than 300 nm in size were successfully developed using the SAS process. Analysis by differential scanning calorimetry and powder X-ray diffraction showed that celecoxib existed in the amorphous form within the solid dispersion nanoparticles fabricated using the SAS process. The celecoxib-PVP-TPGS solid dispersion nanoparticles significantly enhanced in vitro dissolution and oral absorption of celecoxib relative to that of the unprocessed form. The area under the concentration-time curve (AUC0→24 h and peak plasma concentration (Cmax increased 4.6 and 5.7 times, respectively, with the celecoxib-PVP-TPGS formulation. In addition, in vitro dissolution efficiency was well correlated with in vivo pharmacokinetic parameters. The present study demonstrated that formulation of celecoxib-PVP-TPGS solid dispersion nanoparticles using the SAS process is a highly effective strategy for enhancing the bioavailability of poorly water-soluble celecoxib.

  9. Nanoparticle formulations of histone deacetylase inhibitors for effective chemoradiotherapy in solid tumors.

    Science.gov (United States)

    Wang, Edina C; Min, Yuanzeng; Palm, Robert C; Fiordalisi, James J; Wagner, Kyle T; Hyder, Nabeel; Cox, Adrienne D; Caster, Joseph M; Tian, Xi; Wang, Andrew Z

    2015-05-01

    Histone deacetylase inhibitors (HDACIs) represent a class of promising agents that can improve radiotherapy in cancer treatment. However, the full therapeutic potential of HDACIs as radiosensitizers has been restricted by limited efficacy in solid malignancies. In this study, we report the development of nanoparticle (NP) formulations of HDACIs that overcome these limitations, illustrating their utility to improve the therapeutic ratio of the clinically established first generation HDACI vorinostat and a novel second generation HDACI quisinostat. We demonstrate that NP HDACIs are potent radiosensitizers in vitro and are more effective as radiosensitizers than small molecule HDACIs in vivo using mouse xenograft models of colorectal and prostate carcinomas. We found that NP HDACIs enhance the response of tumor cells to radiation through the prolongation of γ-H2AX foci. Our work illustrates an effective method for improving cancer radiotherapy treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Amelioration of excision wounds by topical application of green synthesized, formulated silver and gold nanoparticles in albino Wistar rats.

    Science.gov (United States)

    Naraginti, Saraschandra; Kumari, P Lakshmi; Das, Raunak Kumar; Sivakumar, A; Patil, Sagar Hindurao; Andhalkar, Vaibhav Vilas

    2016-05-01

    Wound healing, a complex biological process, has attained a lot of attention as dermatologists are primarily interested in stimulated wound closure without formation of scar or a faint scar. The recent upsurgence of nanotechnology has provided novel therapeutic materials in the form of silver and gold nanoparticles which accelerate the wound healing process. The effect of formulated nanoparticles using Coleus forskohlii root extract (green synthesized) has been tried out for ameliorating full thickness excision wounds in albino Wistar male rats. The evaluation of in vivo activity of nanoparticles in wound healing was carried out on open wounds made by excision on the dorsal sides of albino Wistar rats under anesthesia, and the healing of the wounds was assessed. Histological aspects of the healing process were studied by a HE (Hematoxylin and Eosin) staining method to assess various degrees of re-epithelialization and the linear alignment of the granulation tissue whereas Van Gieson's histochemical staining was performed to observe collagen fibers. The healing action shown by the formulated nanoparticles was remarkable during the early stages of wound healing, which resulted in the substantial reduction of the whole healing period. Topical application of formulated gold nanoparticles was found to be more effective in suppressing inflammation and stimulating re-epithelialization compared to silver nanoparticles during the healing process. The results throw light on the amelioration of excision wounds using nanoparticles which could be a novel therapeutic way of improving wound healing in clinical practice. The mechanism of advanced healing action of both types of nanoparticles could be due to their antimicrobial, antioxidant and anti-inflammatory properties. Copyright © 2016. Published by Elsevier B.V.

  11. Dose ranging, expanded acute toxicity and safety pharmacology studies for intravenously administered functionalized graphene nanoparticle formulations.

    Science.gov (United States)

    Kanakia, Shruti; Toussaint, Jimmy D; Mullick Chowdhury, Sayan; Tembulkar, Tanuf; Lee, Stephen; Jiang, Ya-Ping; Lin, Richard Z; Shroyer, Kenneth R; Moore, William; Sitharaman, Balaji

    2014-08-01

    Graphene nanoparticle dispersions show immense potential as multifunctional agents for in vivo biomedical applications. Herein, we follow regulatory guidelines for pharmaceuticals that recommend safety pharmacology assessment at least 10-100 times higher than the projected therapeutic dose, and present comprehensive single dose response, expanded acute toxicology, toxicokinetics, and respiratory/cardiovascular safety pharmacology results for intravenously administered dextran-coated graphene oxide nanoplatelet (GNP-Dex) formulations to rats at doses between 1 and 500 mg/kg. Our results indicate that the maximum tolerable dose (MTD) of GNP-Dex is between 50 mg/kg ≤ MTD < 125 mg/kg, blood half-life < 30 min, and majority of nanoparticles excreted within 24 h through feces. Histopathology changes were noted at ≥250 mg/kg in the heart, liver, lung, spleen, and kidney; we found no changes in the brain and no GNP-Dex related effects in the cardiovascular parameters or hematological factors (blood, lipid, and metabolic panels) at doses < 125 mg/kg. The results open avenues for pivotal preclinical single and repeat dose safety studies following good laboratory practices (GLP) as required by regulatory agencies for investigational new drug (IND) application. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Influence of the formulation for solid lipid nanoparticles prepared with a membrane contactor.

    Science.gov (United States)

    El-Harati, Assma Ahmed; Charcosset, Catherine; Fessi, Hatem

    2006-01-01

    Solid lipid nanoparticles (SLN) were introduced in the 1990s as an alternative to microemulsions, polymeric nanoparticles, and liposomes. The SLN are reported to have several advantages, i.e., their biocompatibility and their controlled and targeted drug release. In this paper, we present a new process for the preparation of SLN using a membrane contactor to allow large scale production. The lipid phase is pressed, at a temperature above the melting point of the lipid, through the membrane pores allowing the formation of small droplets. The lipid droplets are then detached from the membrane pores by the aqueous phase flowing tangentially to the membrane surface. The SLN are formed by the following cooling of the preparation below the lipid melting point. The influence of the aqueous phase and lipid phase formulations on the lipid phase flux and on the SLN size are studied. It is shown that SLN are obtained with a lipid phase flux between 0.21 and 0.27 m3/h.m2, SLN size between 175 and 260 nm. The advantages of this new process are demonstrated to be its facility of use and its scaling-up ability.

  13. Highly sensitive colorimetric determination of amoxicillin in pharmaceutical formulations based on induced aggregation of gold nanoparticles

    Science.gov (United States)

    Akhond, Morteza; Absalan, Ghodratollah; Ershadifar, Hamid

    2015-05-01

    A novel, simple and highly sensitive colorimetric method is developed for determination of Amoxicillin (AMX). The system is based on aggregation of citrate-capped gold nanoparticles (AuNP) in acetate buffer (pH = 4.5) in the presence of the degradation product of Amoxicillin (DPAMX). It was found that the color of gold nanoparticles changed from red to purple and the intensity of surface plasmon resonance (SPR) peak of AuNPs decreased. A new absorption band was appeared in the wavelength range of 600-700 nm upon addition of DPAMX. The absorbance ratio at the wavelength of 660 and 525 nm (A660/A525) was chosen as the analytical signal indirectly related to AMX concentration. The linearity of the calibration graph was found over the concentration range of 0.3-4.5 μM AMX with a correlation coefficient of 0.9967. Under the optimum experimental conditions, the detection limit was found to be 0.15 μM. The applicability of the method was successfully demonstrated by analysis of AMX in pharmaceutical formulations including capsules and oral suspensions.

  14. Detection and quantitative evaluation of endotoxin contamination in nanoparticle formulations by LAL-based assays.

    Science.gov (United States)

    Neun, Barry W; Dobrovolskaia, Marina A

    2011-01-01

    Bacterial endotoxin or lipopolysaccharide (LPS) is a membrane component of all Gram-negative bacteria. The administration of products contaminated with bacterial endotoxin can cause fever, shock, and even death. Accordingly, the FDA sets limits on the number of endotoxin units (EU) that may be present in a drug or device product. Limulus amoebocyte lysate (LAL) is the extract from amoebocytes of the horseshoe crab Limulus polyphemus, which reacts with bacterial endotoxin. Detection of the products of this reaction is an effective means of quantifying the EU present in a drug formulation. However, nanoparticles frequently interfere with the reactivity of endotoxin, the LAL reaction, or the detection of the reaction products. This interference can be manifested as either an enhancement or an inhibition, causing a respective overestimation or underestimation of the EU in the sample. Here, we present two methods for the detection and quantification of endotoxin in nanoparticle preparations: one is based on an end-point chromogenic LAL assay, and the second approach is based on measuring the turbidity of the LAL extract.

  15. Preparation of an Environmentally Friendly Formulation of the Insecticide Nicotine Hydrochloride through Encapsulation in Chitosan/Tripolyphosphate Nanoparticles.

    Science.gov (United States)

    Yang, Ying; Cheng, Jiagao; Garamus, Vasil M; Li, Na; Zou, Aihua

    2018-02-07

    Insecticide nicotine hydrochloride (NCT) was formulated as nanoparticles composed of chitosan (CS) and sodium tripolyphosphate (TPP) to undermine its adverse impacts on human health and reinforce its physicochemical stability. The study investigated the preparation and characterization of chitosan/tripolyphosphate nanoparticles (CS/TPP NPs) with good encapsulation efficiency (55%), uniform morphology, and physicochemical stability (45 days) through dynamic light scattering (DLS), transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS) measurements. A bioassay against Musca domestica NCT CS/TPP NPs exhibited good bioactivity and thermal stability. The effect of the monovalent salt (NaCl) on manipulating the formation and size distribution of ionically cross-linked nanoparticles was demonstrated as well. The formulation of NCT CS/TPP NPs could be a utility candidate in public health and agriculture.

  16. New Perspective in the Formulation and Characterization of Didodecyldimethylammonium Bromide (DMAB Stabilized Poly(Lactic-co-Glycolic Acid (PLGA Nanoparticles.

    Directory of Open Access Journals (Sweden)

    Rebecca Gossmann

    Full Text Available Over the last few decades the establishment of nanoparticles as suitable drug carriers with the transport of drugs across biological barriers such as the gastrointestinal barrier moved into the focus of many research groups. Besides drug transport such carrier systems are well suited for the protection of drugs against enzymatic and chemical degradation. The preparation of biocompatible and biodegradable nanoparticles based on poly(lactic-co-glycolic acid (PLGA is intensively described in literature, while especially nanoparticles with cationic properties show a promising increased cellular uptake. This is due to the electrostatic interaction between the cationic surface and the negatively charged lipid membrane of the cells. Even though several studies achieved the successful preparation of nanoparticles stabilized with the cationic surfactants such as didodecyldimethylammonium bromide (DMAB, in most cases insufficient attention was paid to a precise analytical characterization of the nanoparticle system. The aim of the present work was to overcome this deficit by presenting a new perspective in the formulation and characterization of DMAB-stabilized PLGA nanoparticles. Therefore these nanoparticles were carefully examined with regard to particle diameter, zeta potential, the effect of variation in stabilizer concentration, residual DMAB content, and electrolyte stability. Without any steric stabilization, the DMAB-modified nanoparticles were sensitive to typical electrolyte concentrations of biological environments due to compression of the electrical double layer in conjunction with a decrease in zeta potential. To handle this problem, the present study proposed two modifications to enable electrolyte stability. Both polyvinyl alcohol (PVA and polyethylene glycol (PEG modified DMAB-PLGA-nanoparticles were stable during electrolyte addition. Furthermore, in contrast to unmodified DMAB-PLGA-nanoparticles and free DMAB, such modifications led to

  17. Microparticulate poly(vinyl alcohol) hydrogel formulations for embedding and controlled release of polyethylenimine (PEI)-based nanoparticles.

    Science.gov (United States)

    Schulze, Jan; Hendrikx, Stephan; Schulz-Siegmund, Michaela; Aigner, Achim

    2016-11-01

    Nucleic acid-based therapeutics offer enormous potential in the treatment of various pathologies. For DNA or RNA delivery, nanoparticle systems based on lipids or polymers have been developed. However, colloidal instability in solution, poor storage properties especially as dry powder and little stability against an aggressive environment, e.g. after oral application, are major issues. Furthermore, there is an urgent need for sustained release systems that allow for fine-tuned, long-term temporal and spatial nanoparticle release. In this paper, we describe the embedding of polymeric nanoparticles for gene delivery, namely polyethylenimine (PEI)-based polyplexes and their corresponding liposome-modified analogues (lipopolyplexes), into microparticulate poly (vinyl alcohol) (PVA) hydrogels. Various parameters are modified, and major differences are found. PVA is explored with two different molecular weights and at different concentrations, furthermore different emulsifiers and acetone for extraction are employed, and the protocol is performed with or without repetitive freeze/thaw cycles for physical PVA crosslinking. We thereby establish Nanoparticles-in-Microparticle Delivery Systems (NiMDS) that are extensively characterized and shown to allow prolonged storage as easy-to-handle formulation (dry powder) without loss of nanoparticle activity. Unexpectedly, the nanoparticles' PVA encapsulation/release alters important physicochemical nanoparticle properties and biological activities in a favourable way. Furthermore, we also demonstrate the nanoparticle release to be dependent on the microstructure of the PVA matrix, which is determined by the degree of physical crosslinking through a defined number of freeze/thaw cycles. We show that these defined physically crosslinked PVA hydrogels thus represent sustained release devices for fine-tuned, long-term nanoparticle release in possible therapeutic applications. The present paper for the first time describes the

  18. Long-circulating polyhydroxybutyrate-co-hydroxyvalerate nanoparticles for tumor targeted docetaxel delivery: Formulation, optimization and in vitro characterization.

    Science.gov (United States)

    Vardhan, Harsh; Mittal, Pooja; Adena, Sandeep Kumar Reddy; Mishra, Brahmeshwar

    2017-03-01

    In the present research an attempt was made to develop and optimize docetaxel-loaded polyhydroxybutyrate-co-hydroxyvalerate (PHBV) nanoparticles, using modified emulsification solvent evaporation technique and design of experiment (DOE) methodology. Formulation of docetaxel-loaded PHBV nanoparticles was conducted by factor screening studies with Plackett-Burman design (PBD) followed by Box-Behnken experimental design (BBD) to evaluate the effect of independent variables on responses. Five most important independent variables were screened out, which were obtained from failure mode effect analysis (FMEA) and factor screening studies. The effect of formulation parameters on selected responses was depicted by 2-D and 3-D response surface methodology (RSM). The final optimized batch was evaluated by various in vitro characterizations. The observed particle size, zeta potential and entrapment efficiency of optimized formulation was found to be 283±2.79nm, -17±2.64mV and 44±0.59% respectively. Morphological studies demonstrated the smooth and spherical shape of nanoparticles. In vitro drug release follows the Peppas-Korsmeyer model of drug release kinetics. Cytotoxicity study was assessed using MCF-7 for percentage inhibition of human breast cancer cell line. These results indicate that the PHBV Nanoparticles could be a promising drug delivery system for efficient prolong drug release. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Formulation, characterization, and expression of a recombinant MOMP Chlamydia trachomatis DNA vaccine encapsulated in chitosan nanoparticles

    Directory of Open Access Journals (Sweden)

    Cambridge CD

    2013-05-01

    Full Text Available Chino D Cambridge, Shree R Singh, Alain B Waffo, Stacie J Fairley, Vida A DennisCenter for NanoBiotechnology Research (CNBR, Alabama State University, Montgomery, AL, USAAbstract: Chlamydia trachomatis is a bacterial sexually transmitted infection affecting millions of people worldwide. Previous vaccination attempts have employed the recombinant major outer membrane protein (MOMP of C. trachomatis nonetheless, with limited success, perhaps, due to stability, degradation, and delivery issues. In this study we cloned C. trachomatis recombinant MOMP DNA (DMOMP and encapsulated it in chitosan nanoparticles (DMCNP using the complex coacervation technique. Physiochemical characterizations of DMCNP included transmission and scanning electron microcopy, Fourier transform infrared and ultraviolet-visible spectroscopy, and zeta potential. Encapsulated DMOMP was 167–250 nm, with a uniform spherical shape and homogenous morphology, and an encapsulation efficiency > 90%. A slow release pattern of encapsulated DMOMP, especially in acidic solution, was observed over 7 days. The zeta potential of DMCNP was ~8.80 mV, which indicated that it was highly stable. Toxicity studies of DMCNP (25–400 µg/mL to Cos-7 cells using the MTT assay revealed minimal toxicity over 24–72 hours with >90% viable cells. Ultra-violet visible (UV-vis spectra indicated encapsulated DMOMP protection by chitosan, whereas agarose gel electrophoresis verified its protection from enzymatic degradation. Expression of MOMP protein in DMCNP-transfected Cos-7 cells was demonstrated via Western blotting and immunofluorescence microscopy. Significantly, intramuscular injection of BALB/c mice with DMCNP confirmed the delivery of encapsulated DMOMP, and expression of the MOMP gene transcript in thigh muscles and spleens. Our data show that encapsulation of DMOMP in biodegradable chitosan nanoparticles imparts stability and protection from enzymatic digestion, and enhances delivery and

  20. Liposomal flucytosine capped with gold nanoparticle formulations for improved ocular delivery.

    Science.gov (United States)

    Salem, Heba F; Ahmed, Sayed M; Omar, Mahmoud M

    2016-01-01

    Nanoliposomes have an organized architecture that provides versatile functions. In this study, liposomes were used as an ocular carrier for nanogold capped with flucytosine antifungal drug. Gold nanoparticles were used as a contrasting agent that provides tracking of the drug to the posterior segment of the eye for treating fungal intraocular endophthalmitis. The nanoliposomes were prepared with varying molar ratios of lecithin, cholesterol, Span 60, a positive charge inducer (stearylamine), and a negative charge inducer (dicetyl phosphate). Formulation F6 (phosphatidylcholine, cholesterol, Span 60, and stearylamine at a molar ratio of 1:1:1:0.15) demonstrated the highest extent of drug released, which reached 7.043 mg/h. It had a zeta potential value of 42.5±2.12 mV and an average particle size approaching 135.1±12.0 nm. The ocular penetration of the selected nanoliposomes was evaluated in vivo using a computed tomography imaging technique. It was found that F6 had both the highest intraocular penetration depth (10.22±0.11 mm) as measured by the computed tomography and the highest antifungal efficacy when evaluated in vivo using 32 infected rabbits' eyes. The results showed a strong correlation between the average intraocular penetration of the nanoparticles capped with flucytosine and the percentage of the eyes healed. After 4 weeks, all the infected eyes (n=8) were significantly healed (Peyes, which proves the efficiency of the nanoliposomes in delivering both the drug and the contrasting agent to the posterior segment of the eye.

  1. Liposomal flucytosine capped with gold nanoparticle formulations for improved ocular delivery

    Directory of Open Access Journals (Sweden)

    Salem HF

    2016-01-01

    Full Text Available Heba F Salem,1 Sayed M Ahmed,2 Mahmoud M Omar3 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; 2Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt; 3Department of Industrial Pharmacy, Faculty of Pharmacy, Deraya University, El-Minia, Egypt Abstract: Nanoliposomes have an organized architecture that provides versatile functions. In this study, liposomes were used as an ocular carrier for nanogold capped with flucytosine antifungal drug. Gold nanoparticles were used as a contrasting agent that provides tracking of the drug to the posterior segment of the eye for treating fungal intraocular endophthalmitis. The nanoliposomes were prepared with varying molar ratios of lecithin, cholesterol, Span 60, a positive charge inducer (stearylamine, and a negative charge inducer (dicetyl phosphate. Formulation F6 (phosphatidylcholine, cholesterol, Span 60, and stearylamine at a molar ratio of 1:1:1:0.15 demonstrated the highest extent of drug released, which reached 7.043 mg/h. It had a zeta potential value of 42.5±2.12 mV and an average particle size approaching 135.1±12.0 nm. The ocular penetration of the selected nanoliposomes was evaluated in vivo using a computed tomography imaging technique. It was found that F6 had both the highest intraocular penetration depth (10.22±0.11 mm as measured by the computed tomography and the highest antifungal efficacy when evaluated in vivo using 32 infected rabbits’ eyes. The results showed a strong correlation between the average intraocular penetration of the nanoparticles capped with flucytosine and the percentage of the eyes healed. After 4 weeks, all the infected eyes (n=8 were significantly healed (P<0.01 when treated with liposomal formulation F6. Overall, the nanoliposomes encapsulating flucytosine have been proven efficient in treating the infected rabbits’ eyes, which proves the efficiency of the

  2. Influence of paints formulations on nanoparticles release during their life cycle

    Science.gov (United States)

    Fiorentino, Brice; Golanski, Luana; Guiot, Arnaud; Damlencourt, Jean-François; Boutry, Delphine

    2015-03-01

    Pristine nanoparticles (NPs) may present a hazard to humans and the environment, and hence it is important to know to what extent NPs can be freely released from commercialized products in which they are added. The purpose of this study was to identify the parameters of the paint formulation containing SiO2 NPs of 19-nm diameter that could have an impact on the release induced by aging and abrasion. In order to simulate outdoor aging during the life cycle of the product, painted panels were exposed to accelerated weathering experiments in accordance with the norm EN ISO 16474-3:2013. The surface modification of these paints was characterized by scanning electron microscope coupled with energy dispersive spectrometry (SEM-EDS). These analyses showed that the acrylic copolymer binder has undergone a more significant chemical degradation compared with the styrene-acrylic copolymer. To simulate a mechanical aging, abrasion tests were conducted using a Taber Abraser, simulating critical scenarios of the abrasion standard. The particle size distributions and particle concentrations of the abraded particles were measured using an electric low-pressure impactor. After accelerated aging and abrasion tests, we observed a link between the paint degradations occurring with the release of pristine NPs and the embedded pristine NPs. Surface degradation of acrylic copolymer paints was more significant than that of the styrene-acrylic copolymer paints, and this induced a release of NPs 2.7 times higher. Other parameters like TiO2 addition as pigments induced a strong stability of paint against light and water, decreasing the total number of NPs released from paints from 30,000 to 1200 particles/cm3. These results revealed that formulations can be tuned to decrease the number of free NPs released and get a "safe-by-design" product.

  3. Influence of paints formulations on nanoparticles release during their life cycle

    Energy Technology Data Exchange (ETDEWEB)

    Fiorentino, Brice, E-mail: brice.fiorentino@cea.fr; Golanski, Luana; Guiot, Arnaud; Damlencourt, Jean-François; Boutry, Delphine [Commissariat à l’énergie atomique et aux énergies alternatives (France)

    2015-03-15

    Pristine nanoparticles (NPs) may present a hazard to humans and the environment, and hence it is important to know to what extent NPs can be freely released from commercialized products in which they are added. The purpose of this study was to identify the parameters of the paint formulation containing SiO{sub 2} NPs of 19-nm diameter that could have an impact on the release induced by aging and abrasion. In order to simulate outdoor aging during the life cycle of the product, painted panels were exposed to accelerated weathering experiments in accordance with the norm EN ISO 16474-3:2013. The surface modification of these paints was characterized by scanning electron microscope coupled with energy dispersive spectrometry (SEM–EDS). These analyses showed that the acrylic copolymer binder has undergone a more significant chemical degradation compared with the styrene-acrylic copolymer. To simulate a mechanical aging, abrasion tests were conducted using a Taber Abraser, simulating critical scenarios of the abrasion standard. The particle size distributions and particle concentrations of the abraded particles were measured using an electric low-pressure impactor. After accelerated aging and abrasion tests, we observed a link between the paint degradations occurring with the release of pristine NPs and the embedded pristine NPs. Surface degradation of acrylic copolymer paints was more significant than that of the styrene-acrylic copolymer paints, and this induced a release of NPs 2.7 times higher. Other parameters like TiO{sub 2} addition as pigments induced a strong stability of paint against light and water, decreasing the total number of NPs released from paints from 30,000 to 1200 particles/cm{sup 3}. These results revealed that formulations can be tuned to decrease the number of free NPs released and get a “safe-by-design” product.

  4. Nano-sized cosmetic formulations or solid nanoparticles in sunscreens: a risk to human health?

    Science.gov (United States)

    Nohynek, Gerhard J; Dufour, Eric K

    2012-07-01

    Personal care products (PCP) often contain micron- or nano-sized formulation components, such as nanoemulsions or microscopic vesicles. A large number of studies suggest that such vesicles do not penetrate human skin beyond the superficial layers of the stratum corneum. Nano-sized PCP formulations may enhance or reduce skin absorption of ingredients, albeit at a limited scale. Modern sunscreens contain insoluble titanium dioxide (TiO₂) or zinc oxide (ZnO) nanoparticles (NP), which are efficient filters of UV light. A large number of studies suggest that insoluble NP do not penetrate into or through human skin. A number of in vivo toxicity tests, including in vivo intravenous studies, showed that TiO₂ and ZnO NP are non-toxic and have an excellent skin tolerance. Cytotoxicity, genotoxicity, photo-genotoxicity, general toxicity and carcinogenicity studies on TiO₂ and ZnO NP found no difference in the safety profile of micro- or nano-sized materials, all of which were found to be non-toxic. Although some published in vitro studies on insoluble nano- or micron-sized particles suggested cell uptake, oxidative cell damage or genotoxicity, these data are consistent with those from micron-sized particles and should be interpreted with caution. Data on insoluble NP, such as surgical implant-derived wear debris particles or intravenously administered magnetic resonance contrast agents suggest that toxicity of small particles is generally related to their chemistry rather than their particle size. Overall, the weight of scientific evidence suggests that insoluble NP used in sunscreens pose no or negligible risk to human health, but offer large health benefits, such as the protection of human skin against UV-induced skin ageing and cancer.

  5. Nanoparticle formulation by Büchi B-90 Nano Spray Dryer for oral mucoadhesion.

    Science.gov (United States)

    Harsha, Sree N; Aldhubiab, Bander E; Nair, Anroop B; Alhaider, Ibrahim Abdulrahman; Attimarad, Mahesh; Venugopala, Katharigatta N; Srinivasan, Saminathan; Gangadhar, Nagesh; Asif, Afzal Haq

    2015-01-01

    Diabetes is considered one of the main threats to global public health in this era. It is increasing rapidly in every part of the world; the prevalence of the disease will grow to the point where 366 million people will be affected by 2030. The prevalence of diabetes mellitus (DM) in the Saudi population is high, and the majority of patients suffer from type 2 DM. Marketed oral antidiabetic drugs have indicated poor tolerability during chronic treatments, and this contributes to the moderately large proportion of type 2 DM patients that remain inadequately managed. Vildagliptin nanospheres were prepared with aminated gelatin using a spray-drying method; narrow particle-size distribution was seen at 445 nm. The angle of repose was found to be θ <33.5°. The nanospheres appeared to be spherical with a smooth surface. The drug content and percentage yield of the nanospheres were found to be 76.2%±4.6% and 83%±2%, respectively. The nanosphere-swell profile was found to be 165%±7%. The pure drug was 100% dissolved in 30 minutes, and the nanosphere formulation took 12 hours to dissolve (97.5%±2%), and followed a Korsmeyer-Peppas kinetic model with an R (2) of 0.9838. The wash-off test of nanospheres found that they exhibited an excellent mucoadhesive property at 86.7% for 8 hours. The stability-study data showed no changes in the physicochemical properties of the nanospheres, and suggested that the nanospheres be stored below room temperature. The amount of vildagliptin retained was 1.6% within 3 hours, and in comparison with the gelatin vildagliptin nanoparticles formulation, the percentage that was retained was much higher (98.2% in 12 hours).

  6. Formulation of carbapenems loaded gold nanoparticles to combat multi-antibiotic bacterial resistance: In vitro antibacterial study.

    Science.gov (United States)

    Shaker, Mohamed A; Shaaban, Mona I

    2017-06-15

    Despite the fact that carbapenems (powerful β-lactams antibiotics) were able to fight serious infectious diseases, nowadays the spread of carbapenems-resistant bacteria is considered the main challenge in antibacterial therapy. In this study, we focused on evaluating the surface conjugation of carbapenems (imipenem and meropenem) with gold nanoparticles as a delivering strategy to specifically and safely maximize their therapeutic efficacy while destroying the developing resistance of the pathogens. Different particle size formulae (35, 70 and 200nm) were prepared by citrate reduction method. The prepared nanoparticles were functionalized with imipenem (Ipm) or meropenem (Mem) and physico-chemically characterized for loading efficiency, particle size, morphology, and in-vitro release. The antibacterial efficacy was also evaluated against carbapenems resistant Gram-negative bacteria isolated from infected human, through measuring the minimum inhibitory concentration and antibiotic kill test. All the obtained gold nanoparticles showed a distinct nano-size with loading efficiency up to 72% and 74% for Ipm and Mem, respectively. The conjugation and physico-chemical stability of the formulated carbapenems were confirmed by FTIR and X-RPD. Diffusion driven release behavior was observed for both Ipm and Mem from all of the loaded gold nanoparticles. For both Ipm and Mem, formula with 35nm diameter showed the most significant enhancement in antibacterial activity against all the selected isolates including Klebsiella pneumoniae, Proteus mirabilis and Acinteobacter baumanii. Ipm loaded Gold nanoparticles demonstrated decrease in the MIC of Ipm down to four folds, whereas, Mem loaded gold nanoparticles showed decrease in the MIC of Mem down to three folds on the tested bacterial isolates. Based on these results, the formulation of carbapenems-loaded gold nanoparticles demonstrated to be a promising nano-size delivery vehicle for improving the therapeutic activity and

  7. SN-38 loading capacity of hydrophobic polymer blend nanoparticles: formulation, optimization and efficacy evaluation.

    Science.gov (United States)

    Dimchevska, Simona; Geskovski, Nikola; Petruševski, Gjorgji; Chacorovska, Marina; Popeski-Dimovski, Riste; Ugarkovic, Sonja; Goracinova, Katerina

    2017-03-01

    One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle (NP) core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to NPs prepared using individual polymers. D-optimal design was applied to optimize PLGA/PCL ratio in the polymer blend and the mode of addition of the amphiphilic copolymer Lutrol ® F127 in order to maximize SN-38 loading and obtain NPs with acceptable size for passive tumor targeting. Drug/polymer and polymer/polymer interaction analysis pointed to high degree of compatibility and miscibility among both hydrophobic polymers, providing core configuration with higher drug loading capacity. Toxicity studies outlined the biocompatibility of the blank NPs. Increased in vitro efficacy of drug-loaded NPs compared to the free drug was confirmed by growth inhibition studies using SW-480 cell line. Additionally, the optimized NP formulation showed very promising blood circulation profile with elimination half-time of 7.4 h.

  8. Improvement in bone properties by using risedronate adsorbed hydroxyapatite novel nanoparticle based formulation in a rat model of osteoporosis.

    Science.gov (United States)

    Sahana, H; Khajuria, Deepak Kumar; Razdan, Rema; Mahapatra, D Roy; Bhat, M R; Suresh, Sarasija; Rao, R Ramachandra; Mariappan, L

    2013-02-01

    A superior drug formulation capable of achieving efficient osteogenesis is in imperative demand for the treatment of osteoporosis. In the present study we investigated the potential of using novel risedronate-hydroxyapatite (HA) nanoparticle based formulation in an animal model of established osteoporosis. Nanoparticles of HA loaded with risedronate (NHLR) of various sizes (80-130 nm) were generated for bone targeted drug delivery. Three months after ovariectomy, 36 ovariectomized (OVX) rats were divided into 6 equal groups and treated with various doses of NHLR (500, 350 and 250 microg/kg intravenous single dose) and sodium risedronate (500 microg/kg, intravenous single dose). Untreated OVX and sham OVX served as controls. One month after drug administration, the left tibia and femur were tested for bone mechanical properties and histology, respectively. In the right femur, bone density was measured by method based on Archimedes principle and bone porosity analyses were performed using X-ray imaging. NHLR (250 microg/kg) showed a significant increase in bone density and reduced bone porosity when compared with OVX control. Moreover, NHLR (250 microg/kg) significantly increased bone mechanical properties and bone quality when compared with OVX control. The results strongly suggest that the NHLR, which is a novel nanoparticle based formulation, has a therapeutic advantage over risedronate sodium monotherapy for the treatment of osteoporosis in a rat model of postmenopausal osteoporosis.

  9. Poly(D,L-lactide-co-glycolide) Nanoparticle Agglomerates as Carriers in Dry Powder Aerosol Formulation of Proteins

    Science.gov (United States)

    Peek, Laura J.; Roberts, Lydia; Berkland, Cory

    2013-01-01

    A dry powder aerosol drug delivery system was designed with both nano- and microstructure to maximize the protein loading via surface adsorption and to facilitate delivery to the deep lung, respectively. Ovalbumin was employed as a model protein to adsorb to and controllably flocculate DOTAP-coated PLG nanoparticles into “nanoclusters” possessing low density microstructure. The mechanism of nanoparticle flocculation was probed by evaluating the effects of ionic strength, shear force, and protein concentration on the geometric and aerodynamic diameters of the nanoclusters as well as the protein adsorption efficiency. Salt ions were found to compete with ovalbumin adsorption to nanoparticles and facilitate flocculation; therefore, formulation of nanoclusters for inhaled drug delivery may require the lowest possible ionic strength to maximize protein adsorption. Additional factors, such as shear force and total protein–particle concentration can be altered to optimize nanocluster size, suggesting the possibility of regional lung delivery. Immediate release of ovalbumin was observed, and native protein structure upon release was confirmed by circular dichroism and fluorescence spectroscopy studies. Controlled flocculation of nanoparticles may provide a useful alternative to spray drying when formulating dry powders for pulmonary or nasal administration of protein therapeutics or antigens. PMID:18680321

  10. Nanoparticle formulation by Büchi B-90 Nano Spray Dryer for oral mucoadhesion

    Directory of Open Access Journals (Sweden)

    Harsha SN

    2015-01-01

    temperature. The amount of vildagliptin retained was 1.6% within 3 hours, and in comparison with the gelatin vildagliptin nanoparticles formulation, the percentage that was retained was much higher (98.2% in 12 hours. Keywords: nanospheres, vildagliptin, Büchi Nano Spray Dryer, diabetes

  11. Encapsulation of Alpha-1 antitrypsin in PLGA nanoparticles: In Vitro characterization as an effective aerosol formulation in pulmonary diseases

    Directory of Open Access Journals (Sweden)

    Pirooznia Nazanin

    2012-05-01

    Full Text Available Abstract Background Alpha 1- antitrypsin (α1AT belongs to the superfamily of serpins and inhibits different proteases. α1AT protects the lung from cellular inflammatory enzymes. In the absence of α1AT, the degradation of lung tissue results to pulmonary complications. The pulmonary route is a potent noninvasive route for systemic and local delivery. The aerosolized α1AT not only affects locally its main site of action but also avoids remaining in circulation for a long period of time in peripheral blood. Poly (D, L lactide-co glycolide (PLGA is a biodegradable and biocompatible polymer approved for sustained controlled release of peptides and proteins. The aim of this work was to prepare a wide range of particle size as a carrier of protein-loaded nanoparticles to deposit in different parts of the respiratory system especially in the deep lung. Various lactide to glycolide ratio of the copolymer was used to obtain different release profile of the drug which covers extended and rapid drug release in one formulation. Results Nonaqueous and double emulsion techniques were applied for the synthesis of nanoparticles. Nanoparticles were characterized in terms of surface morphology, size distribution, powder X-ray diffraction (XRD, encapsulation efficiency, in vitro drug release, FTIR spectroscopy and differential scanning calorimetry (DSC. To evaluate the nanoparticles cytotoxicity, cell cytotoxicity test was carried out on the Cor L105 human epithelial lung cancer cell line. Nanoparticles were spherical with an average size in the range of 100 nm to 1μ. The encapsulation efficiency was found to be higher when the double emulsion technique was applied. XRD and DSC results indicated that α1AT encapsulated in the nanoparticles existed in an amorphous or disordered-crystalline status in the polymer matrix. The lactic acid to glycolic acid ratio affects the release profile of α1AT. Hence, PLGA with a 50:50 ratios exhibited the ability to release

  12. Calcium hydroxide nanoparticles for the conservation of cultural heritage: new formulations for the deacidification of cellulose-based artifacts

    Science.gov (United States)

    Poggi, G.; Toccafondi, N.; Melita, L. N.; Knowles, J. C.; Bozec, L.; Giorgi, R.; Baglioni, P.

    2014-03-01

    Alkaline earth metal hydroxide nanoparticles dispersions have demonstrated to be efficient for the preservation of cellulose-based artifacts, providing a stable neutral environment and, if in excess, turning into mild alkaline species. New formulations tailored for specific conservation issues have been recently obtained via a solvothermal reaction, starting from bulk metal, and short chain alcohols. Using this synthetic procedure, stable, and high concentrated calcium hydroxide nanoparticles dispersions can be obtained. The characterization of nanoparticles was carried out by dynamic light scattering, transmission electron microscopy and X-ray powder diffraction and showed that the dispersed systems are particularly suitable for the application on porous substrates. In a direct application of this technology, acidic paper and canvas samples were artificially aged after deacidification using calcium hydroxide nanoparticles dispersed in short chain alcohols. Cellulose viscosimetric polymerization degree (DPv), cellulose pyrolysis temperature, and samples' pH were evaluated upon the aging and in terms of protective action arising from the applied treatment. In particular, determinations of DPv clearly showed that the degradation of acidic paper and canvas samples proceeds at higher rates with respect to deacidified samples. These evidences were also confirmed by the thermogravimetric analysis of samples, in which the benefits due to the deacidification treatments are measured in terms of pyrolysis temperature of cellulose. These new formulations of nanoparticles dispersions expand the palette of available tools for the conservation of cellulose-based works of art, such as easel paintings, and manuscripts, potentially opening the way for the intervention on parchment and leather, whose preservation is a particularly challenging task.

  13. Application of quality by design approach to optimize process and formulation parameters of rizatriptan loaded chitosan nanoparticles

    Directory of Open Access Journals (Sweden)

    Ajinath Eknath Shirsat

    2015-01-01

    Full Text Available The purpose of present study was to optimize rizatriptan (RZT chitosan (CS nanoparticles using ionic gelation method by application of quality by design (QbD approach. Based on risk assessment, effect of three variables, that is CS %, tripolyphosphate % and stirring speed were studied on critical quality attributes (CQAs; particle size and entrapment efficiency. Central composite design (CCD was implemented for design of experimentation with 20 runs. RZT CS nanoparticles were characterized for particle size, polydispersity index, entrapment efficiency, in-vitro release study, differential scanning calorimetric, X-ray diffraction, scanning electron microscopy (SEM. Based on QbD approach, design space (DS was optimized with a combination of selected variables with entrapment efficiency > 50% w/w and a particle size between 400 and 600 nm. Validation of model was performed with 3 representative formulations from DS for which standard error of − 0.70-3.29 was observed between experimental and predicted values. In-vitro drug release followed initial burst release 20.26 ± 2.34% in 3-4 h with sustained drug release of 98.43 ± 2.45% in 60 h. Lower magnitude of standard error for CQAs confirms the validation of selected CCD model for optimization of RZT CS nanoparticles. In-vitro drug release followed dual mechanism via, diffusion and polymer erosion. RZT CS nanoparticles were prepared successfully using QbD approach with the understanding of the high risk process and formulation parameters involved and optimized DS with a multifactorial combination of critical parameters to obtain predetermined RZT loaded CS nanoparticle specifications.

  14. In vivo efficacy and toxicity evaluation of polycaprolactone nanoparticles and aluminum based admixture formulation as vaccine delivery system.

    Science.gov (United States)

    Bansal, Vivek; Kumar, Manoj; Bhardwaj, Arun; Brahmne, H G; Singh, Harpal

    2015-10-13

    Delivery of antigen through admixture formulation containing poly caprolactone (PCL) and aluminum phosphate was studied as a promising strategy to generate antigen specific immune response. The present study demonstrates the synergistic effect of admixture formulation of PCL with reduced aluminum (PCL-Al 0.2 mg-TT and PCL-PEG-Al 0.2 mg-TT) as a potential adjuvant system using tetanus toxoid (TT) as a model antigen. On evaluation of the magnitude of efficacy for the proposed formulation by ELISA as well as challenge method, persistent and strong antibody response was obtained throughout the 180 day study period on storage at 5 ± 3 °C. In comparison to the aluminum phosphate based conventional tetanus vaccine, higher levels of IFN-γ and IL-4 were obtained with PCL-Al 0.2 mg-TT and PCL-PEG-Al 0.2 mg-TT, indicating the presence of cell mediated as well as humoral immune responses. Histopathology and serum biochemistry profile in mice further indicated the suitability of the proposed formulation. Percent adsorption/encapsulation of the antigen also increased to nearly 95% in the admixture formulation compared to 55% adsorption in the conventional tetanus vaccine. The present study established a useful baseline for designing biocompatible and effective delivery system for toxoid vaccines through judicious use of PCL based biodegradable nanoparticles in combination with aluminum phosphate. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Brain delivery of camptothecin by means of solid lipid nanoparticles: Formulation design, in vitro and in vivo studies

    DEFF Research Database (Denmark)

    Martins, S.; Tho, I.; Reimold, I.

    2012-01-01

    For the purpose of brain delivery upon intravenous injection, formulations of camptothecin-loaded solid lipid nanoparticles (SLN), prepared by hot high pressure homogenisation, were designed. Incorporation of camptothecin in the hydrophobic and acidic environment of SLN matrix was chosen to stabi......For the purpose of brain delivery upon intravenous injection, formulations of camptothecin-loaded solid lipid nanoparticles (SLN), prepared by hot high pressure homogenisation, were designed. Incorporation of camptothecin in the hydrophobic and acidic environment of SLN matrix was chosen...... to stabilise the lactone ring, which is essential for its antitumour activity, and for avoiding premature loss of drug on the way to target camptothecin to the brain. A multivariate approach was used to assess the influence of the qualitative and quantitative composition on the physicochemical properties...... of camptothecin-loaded SLN in comparison to plain SLN. Mean particle sizes of 90%) were achieved for the most suitable formulations. In vitro release studies in plasma, showed a prolonged release profile of camptothecin from SLN, confirming the physical stability of the particles under physiological pH. A higher...

  16. Formulation and in-vitro evaluation of pantoprazole loaded pH-sensitive polymeric nanoparticles

    Directory of Open Access Journals (Sweden)

    Ahmed Mohammed Nasef

    2017-12-01

    Our results suggested that nanoprecipitation method is effective to produce pH-sensitive polymeric nanoparticles, which can be used as a delivery system for acid labile drug (Pantoprazole to avoid its degradation in acidic medium of the stomach.

  17. A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

    Science.gov (United States)

    Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

    2011-01-01

    Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics. PMID:21720502

  18. Synergistic combination of antioxidants, silver nanoparticles and chitosan in a nanoparticle based formulation: Characterization and cytotoxic effect on MCF-7 breast cancer cell lines.

    Science.gov (United States)

    Nayak, Debasis; Minz, Aliva Prity; Ashe, Sarbani; Rauta, Pradipta Ranjan; Kumari, Manisha; Chopra, Pankaj; Nayak, Bismita

    2016-05-15

    Chitosan (Cs) is a biocompatible, biodegradable cationic polymer having the ability of targeted drug delivery. Vitamin E and C are not synthesized in our body thus, when encapsulated within a carrier system these vitamins in combination with/alone can be utilized for their anti-cancer potentials. The present investigation was conducted to develop a stable nanoparticle based formulation encapsulating antioxidants (Vitamin E, catechol) and silver nanoparticles synthesized from Hibiscus rosa-sinensis (HRS) petal extracts within a chitosan matrix. The prepared nanoformulations were characterized using Field emission scanning electron microscopy (Fe-SEM), X-ray diffraction (XRD) and Attenuated Total Reflection Fourier Transform Infrared spectroscopy (ATR-FTIR). They were further tested for their antioxidant potentials using DPPH assay, hydrogen peroxide scavenging assay, nitric oxide scavenging assay and ferrous antioxidant reducing potential assay. The nanoformulations were found to be highly hemocompatible and showed high encapsulation efficiency up to 76%. They also showed higher antioxidant activity than their base materials. Further, their anti-cancer efficacy was observed against MCF-7 breast cancer cells having IC50 values of 53.36±0.36μg/mL (chitosan-ascorbic acid-glucose), 55.28±0.85μg/mL (chitosan-Vitamin E), 63.72±0.27μg/mL (Chitosan-catechol) and 58.53±0.55μg/mL (chitosan-silver nanoparticles). Thus, the prepared formulations can be therapeutically applied for effective and targeted delivery in breast cancer treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Characterization of Articaine-Loaded Poly(ε-caprolactone) Nanocapsules and Solid Lipid Nanoparticles in Hydrogels for Topical Formulations.

    Science.gov (United States)

    Melo, Nathalie Ferreira Silva de; Campos, Estefânia Vangelie Ramos; Franz-Montan, Michelle; Paula, Eneida de; Silva, Camila Morais Gonçalves da; Maruyama, Cíntia Rodrigues; Stigliani, Tatiane Pasquoto; Lima, Renata de; Araújo, Daniele Ribeiro de; Fraceto, Leonardo Fernandes

    2018-06-01

    This work describes the development of poly-ε-caprolactone nanocapsules (PCL-NC) and solid lipid nanoparticles (SLN) aiming delivery for articaine (ATC), in order to improve its chemical stability in semi-solid preparations looking forward their use for skin delivery. The nanoparticles were characterized by size, polydispersity index, and pH. Cellular viability was evaluated using the MTT test and the in vitro release kinetics was determined using a two-compartment model. The hydrogels with nanoparticle suspensions were characterized considering their rheological aspects and in vitro permeation across artificial membranes. Colloidal stability was satisfactory, since the formulations did not present major alterations during 120 days. High ATC encapsulation was achieved (78% for PCL-NC and 65% for SLN). The release profile of PCL-NC-ATC was slower, compared to the free molecule and SLN-ATC. MTT experiments showed the nanosystems were capable to increase cellular viability compared with free ATC. The hydrogels showed good consistency, homogeneity, and stability and presented pseudoplastic behavior with thixotropy, improving drug efficacy in clinical applications. The gel based on PCL-NC showed faster onset of activity and flux of 35.68 ± 1.98 μg/cm2/h, which then continued for up to 8 h. This study opens up prospects for employment of nanoparticulate systems for modified release of ATC.

  20. Comparative evaluation of antibacterial activity of caffeic acid phenethyl ester and PLGA nanoparticle formulation by different methods

    Science.gov (United States)

    Arasoglu, Tülin; Derman, Serap; Mansuroglu, Banu

    2016-01-01

    The aim of the present study was to evaluate the antimicrobial activity of nanoparticle and free formulations of the CAPE compound using different methods and comparing the results in the literature for the first time. In parallel with this purpose, encapsulation of CAPE with the PLGA nanoparticle system (CAPE-PLGA-NPs) and characterization of nanoparticles were carried out. Afterwards, antimicrobial activity of free CAPE and CAPE-PLGA-NPs was determined using agar well diffusion, disk diffusion, broth microdilution and reduction percentage methods. P. aeroginosa, E. coli, S. aureus and methicillin-resistant S. aureus (MRSA) were chosen as model bacteria since they have different cell wall structures. CAPE-PLGA-NPs within the range of 214.0 ± 8.80 nm particle size and with an encapsulation efficiency of 91.59 ± 4.97% were prepared using the oil-in-water (o-w) single-emulsion solvent evaporation method. The microbiological results indicated that free CAPE did not have any antimicrobial activity in any of the applied methods whereas CAPE-PLGA-NPs had significant antimicrobial activity in both broth dilution and reduction percentage methods. CAPE-PLGA-NPs showed moderate antimicrobial activity against S. aureus and MRSA strains particularly in hourly measurements at 30.63 and 61.25 μg ml-1 concentrations (both p 0.05). In the reduction percentage method, in which the highest results of antimicrobial activity were obtained, it was observed that the antimicrobial effect on S. aureus was more long-standing (3 days) and higher in reduction percentage (over 90%). The appearance of antibacterial activity of CAPE-PLGA-NPs may be related to higher penetration into cells due to low solubility of free CAPE in the aqueous medium. Additionally, the biocompatible and biodegradable PLGA nanoparticles could be an alternative to solvents such as ethanol, methanol or DMSO. Consequently, obtained results show that the method of selection is extremely important and will influence the

  1. Comparative evaluation of antibacterial activity of caffeic acid phenethyl ester and PLGA nanoparticle formulation by different methods

    International Nuclear Information System (INIS)

    Arasoglu, Tülin; Mansuroglu, Banu; Derman, Serap

    2016-01-01

    The aim of the present study was to evaluate the antimicrobial activity of nanoparticle and free formulations of the CAPE compound using different methods and comparing the results in the literature for the first time. In parallel with this purpose, encapsulation of CAPE with the PLGA nanoparticle system (CAPE-PLGA-NPs) and characterization of nanoparticles were carried out. Afterwards, antimicrobial activity of free CAPE and CAPE-PLGA-NPs was determined using agar well diffusion, disk diffusion, broth microdilution and reduction percentage methods. P. aeroginosa, E. coli, S. aureus and methicillin-resistant S. aureus (MRSA) were chosen as model bacteria since they have different cell wall structures. CAPE-PLGA-NPs within the range of 214.0 ± 8.80 nm particle size and with an encapsulation efficiency of 91.59 ± 4.97% were prepared using the oil-in-water (o–w) single-emulsion solvent evaporation method. The microbiological results indicated that free CAPE did not have any antimicrobial activity in any of the applied methods whereas CAPE-PLGA-NPs had significant antimicrobial activity in both broth dilution and reduction percentage methods. CAPE-PLGA-NPs showed moderate antimicrobial activity against S. aureus and MRSA strains particularly in hourly measurements at 30.63 and 61.25 μg ml −1 concentrations (both p < 0.05), whereas they failed to show antimicrobial activity against Gram-negative bacteria (P. aeroginosa and E. coli, p > 0.05). In the reduction percentage method, in which the highest results of antimicrobial activity were obtained, it was observed that the antimicrobial effect on S. aureus was more long-standing (3 days) and higher in reduction percentage (over 90%). The appearance of antibacterial activity of CAPE-PLGA-NPs may be related to higher penetration into cells due to low solubility of free CAPE in the aqueous medium. Additionally, the biocompatible and biodegradable PLGA nanoparticles could be an alternative to solvents such as

  2. A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

    Directory of Open Access Journals (Sweden)

    Li FQ

    2011-04-01

    Full Text Available Feng-Qian Li1, Cheng Yan2, Juan Bi1, Wei-Lin Lv3, Rui-Rui Ji3, Xu Chen1, Jia-Can Su3, Jin-Hong Hu31Department of Pharmaceutics, Shanghai Eighth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Pharmacy, Bethune International Peace Hospital, Shijiazhuang, People’s Republic of China; 3Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of ChinaAbstract: Scopolamine hydrobromide (SH-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w and loading capacity of 20% (w/w were achieved for the microparticles, which ranged from 2 µm to 8 µm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics.Keywords: scopolamine hydrobromide, chitosan, nanoparticles-in-microparticles system, spray-drying, orally disintegrating tablets

  3. Molecular Mechanism of Enhanced Anticancer Effect of Nanoparticle Formulated LY2835219 via p16-CDK4/6-pRb Pathway in Colorectal Carcinoma Cell Line

    Directory of Open Access Journals (Sweden)

    Xu Tang

    2016-01-01

    Full Text Available LY2835219 is a dual inhibitor to CDK4 and CDK6. This study was to prepare LY2835219-loaded chitosan nanoparticles (CNP/LY and LY2835219-loaded hyaluronic acid-conjugated chitosan nanoparticles (HACNP/LY and revealed their anticancer effect and influence on p16-CDK4/6-pRb pathway against colon cell line. The nanoparticle sizes of CNP/LY and HACNP/LY were approximately 195±39.6 nm and 217±31.1 nm, respectively. The zeta potentials of CNP/LY and HACNP/LY were 37.3±1.5 mV and 30.3±2.2 mV, respectively. And the preparation process showed considerable drug encapsulation efficiency and loading efficiency. LY2835219, CNP/LY, and HACNP/LY inhibited HT29 cell proliferation with 0.68, 0.54, and 0.30 μM of IC50, respectively. G1 phase was arrested by LY2835219 and its formulations. Furthermore, inhibition of CDK4/6 by LY2835219 formulations induced CDK4, CDK6, cyclin D1, and pRb decrease and p16 increase at both protein and mRNA levels. Overall, nanoparticle formulated LY2835219 could enhance the cytotoxicity and cell cycle arrest, and HACNP/LY strengthened the trend furtherly compared to CNP/LY. It is the first time to demonstrate the anticancer effect and mechanism against HT29 by LY2835219 and its nanoparticles. The drug and its nanoparticle formulations delay the cell growth and arrest cell cycle through p16-CDK4/6-pRb pathway, while the nanoparticle formulated LY2835219 could strengthen the process.

  4. Novel formulation and evaluation of a Q10-loaded solid lipid nanoparticle cream: in vitro and in vivo studies

    Directory of Open Access Journals (Sweden)

    Farboud ES

    2011-03-01

    Full Text Available Effat Sadat Farboud, Saman Ahmad Nasrollahi, Zahra TabbakhiDepartment of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, IranAbstract: Solid lipid nanoparticles (SLNs of coenzyme Q10 (CoQ10 were formulated by a high-pressure homogenization method. The best formulation of SLN dispersion consisted of 13% lipid (cetyl palmitate or stearic acid, 8% surfactant (Tween 80 or Tego Care 450, and water. Stability tests, particle size analysis, differential scanning calorimetry, transmission electron microscopy, and release study were conducted to find the best formulation. A simple cream of CoQ10 and a cream containing CoQ10-loaded SLNs were prepared and compared on volunteers aged 20–30 years. SLNs with particle size between 50 nm and100 nm exhibited the most suitable stability. In vitro release profiles of CoQ10 from simple cream, SLN alone, and CoQ10-loaded SLN cream showed prolonged release for SLNs compared with the simple cream, whereas there was no significant difference between SLN alone and SLN in cream. In vitro release studies also demonstrated that CoQ10-loaded SLN and SLN cream possessed a biphasic release pattern in comparison with simple cream. In vivo skin hydration and elasticity studies on 25 volunteers suggested good dermal penetration and useful activity of Q10 on skin as a hydratant and antiwrinkle cream.Keywords: coenzyme Q10, SLN, release study 

  5. Nanoparticle formulation improves the anticonvulsant effect of clonazepam on the pentylenetetrazole-induced seizures: behavior and electroencephalogram.

    Science.gov (United States)

    Leyva-Gómez, Gerardo; González-Trujano, María Eva; López-Ruiz, Edith; Couraud, Pierre-Olivier; Wekslerg, Babette; Romero, Ignacio; Miller, Florence; Delie, Florence; Allémann, Eric; Quintanar-Guerrero, David

    2014-08-01

    To document the efficacy of clonazepam (CLZ) either free as a solution or loaded in solid lipid nanoparticles (CLZ-SLN) or mixed micelles (CLZ-MM), the in vitro blood-brain barrier permeability of the formulations was determined. Behavior and/or electroencephalograms (EEGs) of rodents receiving treatments were also studied. The in vitro permeability of CLZ increased when associated with SLN, but decreased in the case of MM. The occurrence of the pentylenetetrazole (PTZ)-induced seizures in mice was significantly prevented by CLZ, even when exposed a lower dose of CLZ-SLN after administration by the oral route. The behavioral severity and EEGs showing the PTZ-induced paroxystic activity in rats diminished significantly in the presence of CLZ alone (0.3 mg/kg), and were almost totally prevented in the rats treated with CLZ-SLN (equivalent to 0.3 mg/kg). The frequency, duration, and spreading of the spikes-wave of rats treated with CLZ-SLN decreased significantly as compared with CLZ alone, CLZ-MM, or the vehicle. These results show an in vitro-in vivo correlation in the enhanced blood-brain barrier permeability of SLN formulation, and a contribution of MM to the carrier effect of drugs toward the bloodstream and brain, where this pharmaceutical formulation of CLZ-SLN improves the anticonvulsant effect of this benzodiazepine, thus offering additional advantages after oral administration. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. The Effect of Emulation Formulation to Encapsulation of Fe3O4 Magnetic nanoparticle with Poly (Lactic Acid)

    International Nuclear Information System (INIS)

    Evi Yuliyanti; Sudaryanto; Mujamilah; Yoki Yulizar

    2008-01-01

    The research to study the effect of emulsion formulation to encapsulation Fe 3 O 4 magnetic nanoparticle with Poly(Lactic Acid) (PLA) has been done. Microemulsion by ultrasonic probe is used in encapsulation process and continued by solvent evaporation. Emulsion formulation has been varied by changing oil phase volume in the oil in water (o/w) emulsion system from 6 mL, 8 mL, 10 mL, 12 mL and 14 mL, whereas water phase volume is constant (55 mL). Sample characterization is carried on by Scanning Electron Microscope (SEM) to know the morphology and sample size. X-Ray Diffractometer (XRD) is used to identify the phase, Vibrating Sample Magnetometer (VSM) is used to measure magnetic saturation while Neutron Activation Analysis (NAA) is used to measure encapsulation percentage of Fe 3 O 4 with PLA. The smallest nanosphere is resulted by emulsion formulation (o/w) of 14/55 with the main sample size 382 nm. The maximum magnetic saturation of Fe 3 O 4 + PLA nanosphere is 2.556 emu/g and encapsulation percentage is 24.94 %. (author)

  7. Nanoparticle-Laden Contact Lens for Controlled Ocular Delivery of Prednisolone: Formulation Optimization Using Statistical Experimental Design

    Directory of Open Access Journals (Sweden)

    Amr ElShaer

    2016-04-01

    Full Text Available Human eye is one of the most accessible organs in the body, nonetheless, its physiology and associated precorneal factors such as nasolacrimal drainage, blinking, tear film, tear turnover, and induced lacrimation has significantly decreased the residence time of any foreign substances including pharmaceutical dosage forms. Soft contact lenses are promising delivery devices that can sustain the drug release and prolong residence time by acting as a geometric barrier to drug diffusion to tear fluid. This study investigates experimental parameters such as composition of polymer mixtures, stabilizer and the amount of active pharmaceutical ingredient on the preparation of a polymeric drug delivery system for the topical ocular administration of Prednisolone. To achieve this goal, prednisolone-loaded poly (lactic-co-glycolic acid (PLGA nanoparticles were prepared by single emulsion solvent evaporation method. Prednisolone was quantified using a validated high performance liquid chromatography (HPLC method. Nanoparticle size was mostly affected by the amount of co-polymer (PLGA used whereas drug load was mostly affected by amount of prednisolone (API used. Longer homogenization time along with higher amount of API yielded the smallest size nanoparticles. The nanoparticles prepared had an average particle size of 347.1 ± 11.9 nm with a polydispersity index of 0.081. The nanoparticles were then incorporated in the contact lens mixture before preparing them. Clear and transparent contact lenses were successfully prepared. When the nanoparticle (NP-loaded contact lenses were compared with control contact lenses (unloaded NP contact lenses, a decrease in hydration by 2% (31.2% ± 1.25% hydration for the 0.2 g loaded NP contact lenses and light transmission by 8% (unloaded NP contact lenses 94.5% NP 0.2 g incorporated contact lenses 86.23%. The wettability of the contact lenses remained within the desired value (<90 °C even upon incorporation of the NP. NP

  8. Formulation and characterization of solid lipid nanoparticles loaded Neem oil for topical treatment of acne

    Directory of Open Access Journals (Sweden)

    V. Vijayan

    2013-01-01

    Conclusion: The result concluded that Neem oil loaded solid lipid nanoparticles with more lecithin content in their colloid exhibit sustained effect which satisfactorily produced the antibacterial action on Acne microbes. Therefore Neem oil loaded SLN was used successfully for prolonged treatment of Acne.

  9. Ethyl cellulose nanoparticles as a platform to decrease ulcerogenic potential of piroxicam: formulation and in vitro/in vivo evaluation.

    Science.gov (United States)

    El-Habashy, Salma E; Allam, Ahmed N; El-Kamel, Amal H

    2016-01-01

    Nanoparticles (NPs) have long gained significant interest for their use in various drug formulations in order to increase bioavailability, prolong drug release, and decrease side effects of highly toxic drugs. The objective of this investigation was to evaluate the potential of ethyl cellulose-based NPs (EC-NPs) to modulate the release and reduce ulcerogenicity of piroxicam (PX) after oral administration. PX-loaded EC-NPs were prepared by solvent evaporation technique using different stabilizers at three concentration levels. Morphological examination of selected formulas confirmed the formation of spherical NPs with slightly porous surface. Formulation containing poloxamer-stabilized EC-NPs (P188/0.2), having a particle size of 240.26±29.24 nm, polydispersity index of 0.562±0.030, entrapment efficiency of 85.29%±1.57%, and modulated release of PX (88% after 12 hours), was selected as the optimum formulation. Differential scanning calorimetry demonstrated the presence of PX in an amorphous form in the NPs. Fourier-transform infrared spectroscopy revealed the possible formation of hydrogen bond and the absence of chemical interaction. In vivo study, evaluation of pharmacokinetic parameters, evaluation of gastric irritation potential, and histological examination were conducted after administration of the selected formulation. Time to reach maximum plasma concentration, t max, of poloxamer-stabilized EC-NPs was significantly higher than that of Feldene(®) 20 mg capsules (P≤0.001). Encapsulation of the acidic, gastric offender PX into NPs managed to significantly suppress gastric ulceration potential in rats (P≤0.05) as compared to that of PX suspension. A reduction of 66% in mean ulcer index was observed. In conclusion, poloxamer-stabilized EC-NPs (P188/0.2) had a significant potential of offsetting deleterious side effects common in PX use.

  10. Development and characterization of new and scalable topical formulations containing N-acetyl-d-glucosamine-loaded solid lipid nanoparticles.

    Science.gov (United States)

    Marto, Joana; Sangalli, Cecilia; Capra, Priscilla; Perugini, Paola; Ascenso, Andreia; Gonçalves, Lídia; Ribeiro, Helena

    2017-11-01

    N-Acetyl-d-glucosamine (NAG) has been recently considered for topical treatment of hyperpigmentation disorders due to its inhibitory effect on thyrosinase enzymes in melanocytes. NAG is a precursor of hyaluronic acid, increasing its amount in skin, and consequently, preserving the skin hydration and elasticity. It may also act as an emulsion stabilizer. Solid lipid nanoparticles (SLN) are advanced delivery systems successfully used in pharmaceutical and cosmetic formulations for the improvement of active molecules penetration into the skin. Therefore, this work aimed to develop and characterize stable and scalable topical formulations containing NAG-loaded SLN. NAG was incorporated in SLN which were prepared by two high shear homogenizers and characterized regarding its morphology and particle size by transmission electron microscopy and photon correlation spectroscopy, respectively. Oil emulgel and hydrogel were used as carriers of NAG-loaded SLN. Several parameters were evaluated, including the droplet size distribution, rheology, pH and topical delivery by different techniques. It was observed that SLN size was significantly dependent on NAG incorporation and homogenization process. Most tested SLN parameters appeared to be quite suitable, that is, spherical and well-defined SLN with approximately 258 nm and -30 mV. Hereafter, both gels containing SLN presented a pseudoplastic flow. Emulgel formulation containing NAG-loaded SLN allowed a higher NAG permeation through the SC compared to the respective control (about 0.8 μgcm -2  h -1 ). According to the results obtained, it can be suggested that NAG acts as an emulsion stabilizer. This stabilization was also particularly dependent on the homogenizer type which is quite important for scale-up process. This study demonstrated the potential of scalable SLN formulations to improve NAG topical delivery contributing to the improvement of skin properties on several skin disorders.

  11. Ethyl cellulose nanoparticles as a platform to decrease ulcerogenic potential of piroxicam: formulation and in vitro/in vivo evaluation

    Directory of Open Access Journals (Sweden)

    El-Habashy SE

    2016-05-01

    Full Text Available Salma E El-Habashy, Ahmed N Allam, Amal H El-Kamel Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt Abstract: Nanoparticles (NPs have long gained significant interest for their use in various drug formulations in order to increase bioavailability, prolong drug release, and decrease side effects of highly toxic drugs. The objective of this investigation was to evaluate the potential of ethyl cellulose-based NPs (EC-NPs to modulate the release and reduce ulcerogenicity of piroxicam (PX after oral administration. PX-loaded EC-NPs were prepared by solvent evaporation technique using different stabilizers at three concentration levels. Morphological examination of selected formulas confirmed the formation of spherical NPs with slightly porous surface. Formulation containing poloxamer-stabilized EC-NPs (P188/0.2, having a particle size of 240.26±29.24 nm, polydispersity index of 0.562±0.030, entrapment efficiency of 85.29%±1.57%, and modulated release of PX (88% after 12 hours, was selected as the optimum formulation. Differential scanning calorimetry demonstrated the presence of PX in an amorphous form in the NPs. Fourier-transform infrared spectroscopy revealed the possible formation of hydrogen bond and the absence of chemical interaction. In vivo study, evaluation of pharmacokinetic parameters, evaluation of gastric irritation potential, and histological examination were conducted after administration of the selected formulation. Time to reach maximum plasma concentration, tmax, of poloxamer-stabilized EC-NPs was significantly higher than that of Feldene® 20 mg capsules (P≤0.001. Encapsulation of the acidic, gastric offender PX into NPs managed to significantly suppress gastric ulceration potential in rats (P≤0.05 as compared to that of PX suspension. A reduction of 66% in mean ulcer index was observed. In conclusion, poloxamer-stabilized EC-NPs (P188/0.2 had a significant potential of

  12. Green and ecofriendly synthesis of silver nanoparticles: Characterization, biocompatibility studies and gel formulation for treatment of infections in burns.

    Science.gov (United States)

    Jadhav, Kiran; Dhamecha, Dinesh; Bhattacharya, Debdutta; Patil, Mrityunjaya

    2016-02-01

    The current study summarizes a unique green process for the synthesis of silver nanoparticles (AgNPs) by simple treatment of silver nitrate with aqueous extract of Ammania baccifera. Phytosynthesized AgNPs were characterized by various advanced analytical methods and studied for its use against infections associated with burns. Formation of AgNPs was observed by visual color change from colorless to dark brown and confirmed by UV-visible characteristic peak at 436 nm. Zeta potential, particle size and polydispersity index of nano-silver were found to be -33.1 ± 1.12, 112.6 ± 6.8 nm and 0.3 ± 0.06 respectively. XRD spectra revealed crystalline nature of AgNPs whereas TEM confirmed the presence of mixed morphology of AgNPs. The overall approach designated in the present research investigation for the synthesis of AgNPs is based on all 12 principles of green chemistry, in which no man-made chemical other than the silver nitrate was used. Synthesized nano-silver colloidal dispersion was initially tested for minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against a panel of organisms involved in infections associated with burns (Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA) and methicillin resistant S. aureus (MRSA)). MIC and MBC were found to be in range of 0.992 to 7.93 and 7.93 to 31.75 μg/mL respectively. MBC was used for formulation of AgNP gel and tested for its efficacy using agar well diffusion method against PA, SA and MRSA. Comparative bactericidal efficacy of formulated gel (0.03% w/w) and marked formulation Silverex™ ionic (silver nitrate gel 0.2% w/w) showed equal zone of inhibition against all pathogenic bacteria. Formulated AgNP gel consisting of 95% lesser concentration of silver compared to marketed formulation was found to be equally effective against all organisms. Hence, the formulated AgNP gel could serve as a better alternative with least toxicity towards the treatment presently available for

  13. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers. I. Effect of formulation variables on the physicochemical properties, drug release and stability of clotrimazole-loaded nanoparticles.

    Science.gov (United States)

    Das, Surajit; Ng, Wai Kiong; Tan, Reginald B H

    2014-03-14

    The objective of this study was to develop and evaluate solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) utilizing sucrose ester as a stabilizer/emulsifier for the controlled release of drug/active. Both SLNs and NLCs were prepared using different sugar esters to screen out the most suitable stabilizer. Clotrimazole was used as a model active/drug. The effect of different formulation variables on the particle size, polydispersity index and drug encapsulation efficiency of SLNs and NLCs was evaluated and compared. SLNs and NLCs were physicochemically characterized and compared using Cryo-SEM, DSC and XRD. Furthermore, a drug release study of SLNs and NLCs was conducted. Finally, physicochemical stability (size, PI, ZP, EE) of the SLNs and NLCs was checked at 25 ± 2 °C and at 2-8 °C. Among the sucrose esters, D-1216 was found to be most suitable for both SLNs and NLCs. Formulation variables exhibited a significant impact on size, PI and EE of the nanoparticles. SLNs with ∼120 nm size, ∼0.23 PI, ∼I26I mV ZP, ∼87% EE and NLCs with ∼160 nm size, 0.15 PI, ∼I26I mV ZP, ∼88% EE were produced. Cryo-SEM revealed spherical particles with a smooth surface but did not exhibit any difference in surface morphology between SLNs and NLCs. DSC and XRD results demonstrated the disappearance of clotrimazole peak(s) in drug-loaded SLNs and NLCs. Faster drug release was observed from SLNs than NLCs. NLCs were found to be more stable than SLNs in terms of size, PI, EE and drug release. The results indicated that both SLNs and NLCs stabilized with sucrose ester D-1216 can be used as controlled release carriers although NLCs have an edge over SLNs.

  14. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers: I. Effect of formulation variables on the physicochemical properties, drug release and stability of clotrimazole-loaded nanoparticles

    Science.gov (United States)

    Das, Surajit; Kiong Ng, Wai; Tan, Reginald B. H.

    2014-03-01

    The objective of this study was to develop and evaluate solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) utilizing sucrose ester as a stabilizer/emulsifier for the controlled release of drug/active. Both SLNs and NLCs were prepared using different sugar esters to screen out the most suitable stabilizer. Clotrimazole was used as a model active/drug. The effect of different formulation variables on the particle size, polydispersity index and drug encapsulation efficiency of SLNs and NLCs was evaluated and compared. SLNs and NLCs were physicochemically characterized and compared using Cryo-SEM, DSC and XRD. Furthermore, a drug release study of SLNs and NLCs was conducted. Finally, physicochemical stability (size, PI, ZP, EE) of the SLNs and NLCs was checked at 25 ± 2 °C and at 2-8 °C. Among the sucrose esters, D-1216 was found to be most suitable for both SLNs and NLCs. Formulation variables exhibited a significant impact on size, PI and EE of the nanoparticles. SLNs with ˜120 nm size, ˜0.23 PI, ˜I26I mV ZP, ˜87% EE and NLCs with ˜160 nm size, 0.15 PI, ˜I26I mV ZP, ˜88% EE were produced. Cryo-SEM revealed spherical particles with a smooth surface but did not exhibit any difference in surface morphology between SLNs and NLCs. DSC and XRD results demonstrated the disappearance of clotrimazole peak(s) in drug-loaded SLNs and NLCs. Faster drug release was observed from SLNs than NLCs. NLCs were found to be more stable than SLNs in terms of size, PI, EE and drug release. The results indicated that both SLNs and NLCs stabilized with sucrose ester D-1216 can be used as controlled release carriers although NLCs have an edge over SLNs.

  15. Miconazole-loaded solid lipid nanoparticles: formulation and evaluation of a novel formula with high bioavailability and antifungal activity

    Directory of Open Access Journals (Sweden)

    Aljaeid BM

    2016-01-01

    Full Text Available Bader Mubarak Aljaeid,1 Khaled Mohamed Hosny1,2 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt Background and objective: Miconazole is a broad-spectrum antifungal drug that has poor aqueous solubility (<1 µg/mL; as a result, a reduction in its therapeutic efficacy has been reported. The aim of this study was to formulate and evaluate miconazole-loaded solid lipid nanoparticles (MN-SLNs for oral administration to find an innovative way to alleviate the disadvantages associated with commercially available capsules. Methods: MN-SLNs were prepared by hot homogenization/ultrasonication. The solubility of miconazole in different solid lipids was measured. The effect of process variables, such as surfactant types, homogenization and ultrasonication times, and the charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release, antifungal activity against Candida albicans, and in vivo pharmacokinetics were studied in rabbits. Results: The MN-SLN, consisting of 1.5% miconazole, 2% Precirol ATO5, 2.5% Cremophor RH40, 0.5% Lecinol, and 0.1% Dicetylphosphate, had an average diameter of 23 nm with a 90.2% entrapment efficiency. Furthermore, the formulation of MN-SLNs enhanced the antifungal activity compared with miconazole capsules. An in vivo pharmacokinetic study revealed that the bioavailability was enhanced by >2.5-fold. Conclusion: MN-SLN was more efficient in the treatment of candidiasis with enhanced oral bioavailability and could be a promising carrier for the oral delivery of miconazole. Keywords: miconazole, Precirol ATO5, solid lipid nanoparticles, encapsulation, Cremophor RH40, antifungal activity

  16. Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design

    Science.gov (United States)

    Hao, Jifu; Fang, Xinsheng; Zhou, Yanfang; Wang, Jianzhu; Guo, Fengguang; Li, Fei; Peng, Xinsheng

    2011-01-01

    The purpose of the present study was to optimize a solid lipid nanoparticle (SLN) of chloramphenicol by investigating the relationship between design factors and experimental data using response surface methodology. A Box-Behnken design was constructed using solid lipid (X1), surfactant (X2), and drug/lipid ratio (X3) level as independent factors. SLN was successfully prepared by a modified method of melt-emulsion ultrasonication and low temperature-solidification technique using glyceryl monostearate as the solid lipid, and poloxamer 188 as the surfactant. The dependent variables were entrapment efficiency (EE), drug loading (DL), and turbidity. Properties of SLN such as the morphology, particle size, zeta potential, EE, DL, and drug release behavior were investigated, respectively. As a result, the nanoparticle designed showed nearly spherical particles with a mean particle size of 248 nm. The polydispersity index of particle size was 0.277 ± 0.058 and zeta potential was −8.74 mV. The EE (%) and DL (%) could reach up to 83.29% ± 1.23% and 10.11% ± 2.02%, respectively. In vitro release studies showed a burst release at the initial stage followed by a prolonged release of chloramphenicol from SLN up to 48 hours. The release kinetics of the optimized formulation best fitted the Peppas–Korsmeyer model. These results indicated that the chloramphenicol-loaded SLN could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release. PMID:21556343

  17. Solid lipid nanoparticles as effective reservoir systems for long-term preservation of multidose formulations.

    Science.gov (United States)

    Cerreto, Felice; Paolicelli, Patrizia; Cesa, Stefania; Abu Amara, Hend M; D'Auria, Felicia Diodata; Simonetti, Giovanna; Casadei, Maria Antonietta

    2013-06-01

    Cosmetic multidose preparations, as well as pharmaceutical ones, are at risk of contamination by microorganisms, due to their high water content. Besides the risk of contamination during manufacturing, multidose cosmetic preparations may be contaminated by consumers during their use. In this paper, the results of the utilization of nanoparticles as reservoir systems of parabens, the most used class of preservatives, were reported. Two different systems, solid lipid nanoparticles (SLN) made of pure precirol and nanostructured lipid carriers (NLC) made of precirol and almond oil, containing three parabens as single molecules or as a mixture, were prepared and tested. All the systems were characterized for size, polydispersion index, zeta potential and encapsulation efficiency. Release experiments, carried out in steady state and sink conditions, allowed to evidence that both SLN and NLC were able to act as reservoir systems. The antimicrobial activity of the systems was tested against Candida albicans ATCC 10231 with repeat insult tests. The results of the release experiments and the antimicrobial tests showed very low water concentration of parabens still maintaining their antimicrobial activity.

  18. Antimicrobial and antioxidant potentials of biosynthesized colloidal zinc oxide nanoparticles for a fortified cold cream formulation: A potent nanocosmeceutical application.

    Science.gov (United States)

    S, Sonia; H, Linda Jeeva Kumari; K, Ruckmani; M, Sivakumar

    2017-10-01

    Nanocosmeceuticals are promising applications of nanotechnology in personal care industries. Zinc oxide is an inorganic material that is non-toxic and skin compatible with self-cleansing and microbicidal properties. Herein, exploitation of colloidal zinc oxide nanoparticles (ZnONps) as potent biomaterial for a topical formulation of cosmetic and dermatological significance is employed. ZnONps were green synthesized using environmentally benign Adhatoda vasica leaf extract and characterized by UV-Vis absorption spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), high-resolution transmission electron microscopy (HR-TEM) and energy-dispersive X-ray spectroscopy (EDX). The results reveal that the biosynthesized ZnONps exhibit an absorption peak at 352nm. XRD and HR-TEM analyses confirm the hexagonal wurtzite structure of ZnONps with particle size of about 10nm to 12nm. Elemental analysis by EDX confirms the presence of zinc and oxygen. Zeta potential of -24.6mV affirms the stability of nanoparticles. The antibacterial and antifungal activities of biosynthesized ZnONps exhibit mean zone of inhibition from 08.667±0.282 to 21.666±0.447 (mm) and 09.000±0.177 to 19.000±0.307 (mm) respectively, in a dose-dependent manner. The IC 50 value exerted from the antioxidant activity of ZnONps is found to be 139.27μgmL -1 . ZnONps infused cold cream formulation of microbicidal and antioxidant properties was further tested against clinical skin pathogens. The nano-based cold cream exhibited significant inhibitory action against Candida sp., which showed resistance against a commercial antifungal cream (2%). Therefore, this study demonstrates the exploitation of ZnONps as promising colloidal drug carriers in cosmeceuticals that can significantly alleviate human skin infections and oxidative stress induced cellular damage. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Gold Nanoparticle Sensor for the Visual Detection of Pork Adulteration in Meatball Formulation

    Directory of Open Access Journals (Sweden)

    M. E. Ali

    2012-01-01

    Full Text Available We visually identify pork adulteration in beef and chicken meatball preparations using 20 nm gold nanoparticles (GNPs as colorimetric sensors. Meatball is a popular food in certain Asian and European countries. Verification of pork adulteration in meatball is necessary to meet the Halal and Kosher food standards. Twenty nm GNPs change color from pinkish-red to gray-purple, and their absorption peak at 525 nm is red-shifted by 30–50 nm in 3 mM phosphate buffer saline (PBS. Adsorption of single-stranded DNA protects the particles against salt-induced aggregation. Mixing and annealing of a 25-nucleotide (nt single-stranded (ss DNA probe with denatured DNA of different meatballs differentiated well between perfectly matched and mismatch hybridization at a critical annealing temperature. The probes become available in nonpork DNA containing vials due to mismatches and interact with GNPs to protect them from salt-induced aggregation. Whereas, all the pork containing vials, either in pure and mixed forms, consumed the probes totally by perfect hybridization and turned into grey, indicating aggregation. This is clearly reflected by a well-defined red-shift of the absorption peak and significantly increased absorbance in 550–800 nm regimes. This label-free low-cost assay should find applications in food analysis, genetic screening, and homology studies.

  20. An Inhalable Powder Formulation Based on Micro- and Nanoparticles Containing 5-Fluorouracil for the Treatment of Metastatic Melanoma

    Directory of Open Access Journals (Sweden)

    Kelly Cristine Zatta

    2018-01-01

    Full Text Available Melanoma is the most aggressive and lethal type of skin cancer, with a poor prognosis because of the potential for metastatic spread. The aim was to develop innovative powder formulations for the treatment of metastatic melanoma based on micro- and nanocarriers containing 5-fluorouracil (5FU for pulmonary administration, aiming at local and systemic action. Therefore, two innovative inhalable powder formulations were produced by spray-drying using chondroitin sulfate as a structuring polymer: (a 5FU nanoparticles obtained by piezoelectric atomization (5FU-NS and (b 5FU microparticles of the mucoadhesive agent Methocel™ F4M for sustained release produced by conventional spray drying (5FU-MS. The physicochemical and aerodynamic were evaluated in vitro for both systems, proving to be attractive for pulmonary delivery. The theoretical aerodynamic diameters obtained were 0.322 ± 0.07 µm (5FU-NS and 1.138 ± 0.54 µm (5FU-MS. The fraction of respirable particles (FR% were 76.84 ± 0.07% (5FU-NS and 55.01 ± 2.91% (5FU-MS. The in vitro mucoadhesive properties exhibited significant adhesion efficiency in the presence of Methocel™ F4M. 5FU-MS and 5FU-NS were tested for their cytotoxic action on melanoma cancer cells (A2058 and A375 and both showed a cytotoxic effect similar to 5FU pure at concentrations of 4.3 and 1.7-fold lower, respectively.

  1. Fluconazole-loaded solid lipid nanoparticles topical gel for treatment of pityriasis versicolor: formulation and clinical study.

    Science.gov (United States)

    El-Housiny, Shaimaa; Shams Eldeen, Maii Atef; El-Attar, Yasmina Ahmed; Salem, Hoda A; Attia, Dalia; Bendas, Ehab R; El-Nabarawi, Mohamed A

    2018-11-01

    Solid lipid nanoparticles (SLNs) are very potential formulations for topical delivery of antifungal drugs. Hence, the purpose of this research was to formulate the well-known antifungal agent Fluconazole (FLZ)-loaded SLNs topical gel to improve its efficiency for treatment of Pityriasis Versicolor (PV). FLZ-SLNs were prepared by modified high shear homogenization and ultrasonication method using different concentration of solid lipid (Compritol 888 ATO, Precirol ATO5) and surfactant (Cremophor RH40, Poloxamer 407). The physicochemical properties and the in vitro release study for all FLZ-SLNs were investigated. Furthermore, the optimized FLZ-SLN formula was incorporated into gel using Carpobol 934. A randomized controlled clinical trial (RCT) of potential batches was carried out on 30 well diagnosed PV patients comparing to market product Candistan ® 1% cream. Follow up was done for 4 weeks by clinical and KOH examinations. The results showed that FlZ-SLNs were almost spherical shape having colloidal sizes with no aggregation. The drug entrapment efficiency ranged from 55.49% to 83.04%. The zeta potential values lie between -21 and -33 mV presenting good stability. FLZ showed prolonged in vitro release from SLNs dispersion and its Carbapol gel following Higuchi order equation. Clinical studies registered significant improvement (p < .05) in therapeutic response (1.4-fold; healing%, 4-fold; complete eradication) in terms of clinical cure and mycological cure rate from PV against marketed cream. Findings of the study suggest that the developed FLZ loaded SLNs topical gels have superior significant fast therapeutic index in treatment of PV over commercially available Candistan ® cream.

  2. Vitamin E TPGS emulsified vinorelbine bitartrate loaded solid lipid nanoparticles (SLN): Formulation development, optimization and in vitro characterization.

    Science.gov (United States)

    Maurya, Lakshmi; Rajamanickam, Vijayakumar Mahalingam; Narayan, Gopeshwar; Singh, Sanjay

    2018-04-08

    Vinorelbine bitartrate (VRL), a semi synthetic vinca alkaloid approved for breast cancer, has been proved to beneficial as first line and subsequent therapies. However, it's hydrophilic and thermo labile nature provides hindrance to oral clinical translation. The current work focused on the application of DOE a modern statistical optimization tool for the development and optimization of a solid lipid nanoparticle (SLN) formulation that can encapsulate hydrophilic and thermolabile Vinorelbine bitartrate (VRL) to a maximum extent without compromising integrity and anticancer activity of the drug. SLNs were prepared by solvent diffusion technique employing Taguchi orthogonal array design with optimized formulation and process variables. The emulsifying nature and low melting point of glyceryl mono-oleate (GMO) were exploited to enhance entrapment and minimizing temperature associated degradation, respectively. Moreover, two types of surfactants, Vitamin E TPGS (TPGS) and Poloxamer-188 were utilized to obtain TPGS-VRL-SLNs and PL-VRL-SLNs, respectively. The SLNs were characterized for various physicochemical properties, in-vitro drug release kinetics and anticancer activity by MTT assay on MCF-7 cancer cell lines. The SLNs were found to be spherical in shape with entrapment efficiency (EE) up to 58 %. In-vitro release studies showed biphasic release pattern following Korsemeyer peppas model with fickian release kinetics. Results of MTT assay revealed that TPGS-VRL-SLNs and PL-VRL-SLNs were 39.5 and 18.5 fold more effective, respectively, compared to the pristine VRL. DOE approach was successfully applied for the development of VRL-SLNs. Enhanced entrapment and anticancer efficacy of TPGS-VRL-SLN can be attributed to emulsifying nature of GMO and inherent cytotoxic nature of TPGS, respectively, which synergizes with VRL. Therefore, TPGS associated SLNs may be potential carrier in cancer chemotherapeutics. Copyright© Bentham Science Publishers; For any queries, please

  3. A novel immunization approach for dengue infection based on conserved T cell epitopes formulated in calcium phosphate nanoparticles.

    Science.gov (United States)

    Huang, Xiaofang; Karabudak, Aykan; Comber, Joseph D; Philip, Mohan; Morcol, Tulin; Philip, Ramila

    2017-11-02

    Dengue virus (DV) is the etiologic agent of dengue fever, the most significant mosquito-borne viral disease in humans. Most DV vaccine approaches are focused on generating antibody mediated responses; one such DV vaccine is approved for use in humans but its efficacy is limited. While it is clear that T cell responses play important role in DV infection and subsequent disease manifestations, fewer studies are aimed at developing vaccines that induce robust T cells responses. Potent T cell based vaccines require 2 critical components: the identification of specific T cell stimulating MHC associated peptides, and an optimized vaccine delivery vehicle capable of simultaneously delivering the antigens and any required adjuvants. We have previously identified and characterized DV specific HLA-A2 and -A24 binding DV serotypes conserved epitopes, and the feasibility of an epitope based vaccine for DV infection. In this study, we build on those previous studies and describe an investigational DV vaccine using T cell epitopes incorporated into a calcium phosphate nanoparticle (CaPNP) delivery system. This study presents a comprehensive analysis of functional immunogenicity of DV CaPNP/multipeptide formulations in vitro and in vivo and demonstrates the CaPNP/multipeptide vaccine is capable of inducing T cell responses against all 4 serotypes of DV. This synthetic vaccine is also cost effective, straightforward to manufacture, and stable at room temperature in a lyophilized form. This formulation may serve as an effective candidate DV vaccine that protects against all 4 serotypes as either a prophylactic or therapeutic vaccine.

  4. Anti-biofilm activity of chitosan gels formulated with silver nanoparticles and their cytotoxic effect on human fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Pérez-Díaz, M.; Alvarado-Gomez, E. [Facultad de Ciencias Quimicas, Universidad Autonoma de San Luis Potosi (Mexico); Magaña-Aquino, M. [Servicio de Epidemiologia del Hospital Central “Dr. Ignacio Morones Prieto”, San Luis Potosi (Mexico); Sánchez-Sánchez, R.; Velasquillo, C. [Laboratorio de Biotecnologia, Instituto Nacional de Rehabilitacion, Mexico, D.F. (Mexico); Gonzalez, C. [Facultad de Ciencias Quimicas, Universidad Autonoma de San Luis Potosi (Mexico); Ganem-Rondero, A. [Division de Estudios de Posgrado (Tecnologia Farmaceutica), Facultad de Estudios Superiores Cuautitlan, Universidad Nacional Autonoma de Mexico, Cuautitlan Izcalli, Estado de Mexico (Mexico); Martínez-Castañon, G.; Zavala-Alonso, N. [Doctorado en Ciencias Odontológicas Facultad de Estomatologia, UASLP (Mexico); Martinez-Gutierrez, F. [Facultad de Ciencias Quimicas, Universidad Autonoma de San Luis Potosi (Mexico)

    2016-03-01

    The development of multi-species biofilms in chronic wounds is a serious health problem that primarily generates strong resistance mechanisms to antimicrobial therapy. The use of silver nanoparticles (AgNPs) as a broad-spectrum antimicrobial agent has been studied previously. However, their cytotoxic effects limit its use within the medical area. The purpose of this study was to evaluate the anti-biofilm capacity of chitosan gel formulations loaded with AgNPs, using silver sulfadiazine (SSD) as a standard treatment, on strains of clinical isolates, as well as their cytotoxic effect on human primary fibroblasts. Multi-species biofilm of Staphylococcus aureus oxacillin resistant (MRSA) and Pseudomonas aeruginosa obtained from a patient with chronic wound infection were carried out using a standard Drip Flow Reactor (DFR) under conditions that mimic the flow of nutrients in the human skin. Anti-biofilm activity of chitosan gels and SSD showed a log-reduction of 6.0 for MRSA when chitosan gel with AgNPs at a concentration of 100 ppm was used, however it was necessary to increase the concentration of the chitosan gel with AgNPs to 1000 ppm to get a log-reduction of 3.3, while the SSD showed a total reduction of both bacteria in comparison with the negative control. The biocompatibility evaluation on primary fibroblasts showed better results when the chitosan gels with AgNPs were tested even in the high concentration, in contrast with SSD, which killed all the primary fibroblasts. In conclusion, chitosan gel formulations loaded with AgNPs effectively prevent the formation of biofilm and kill bacteria in established biofilm, which suggest that chitosan gels with AgNPs could be used for prevention and treatment of infections in chronic wounds. The statistic significance of the biocompatibility of chitosan gel formulations loaded with AgNPs represents an advance; however further research and development are necessary to translate this technology into therapeutic and

  5. Anti-biofilm activity of chitosan gels formulated with silver nanoparticles and their cytotoxic effect on human fibroblasts

    International Nuclear Information System (INIS)

    Pérez-Díaz, M.; Alvarado-Gomez, E.; Magaña-Aquino, M.; Sánchez-Sánchez, R.; Velasquillo, C.; Gonzalez, C.; Ganem-Rondero, A.; Martínez-Castañon, G.; Zavala-Alonso, N.; Martinez-Gutierrez, F.

    2016-01-01

    The development of multi-species biofilms in chronic wounds is a serious health problem that primarily generates strong resistance mechanisms to antimicrobial therapy. The use of silver nanoparticles (AgNPs) as a broad-spectrum antimicrobial agent has been studied previously. However, their cytotoxic effects limit its use within the medical area. The purpose of this study was to evaluate the anti-biofilm capacity of chitosan gel formulations loaded with AgNPs, using silver sulfadiazine (SSD) as a standard treatment, on strains of clinical isolates, as well as their cytotoxic effect on human primary fibroblasts. Multi-species biofilm of Staphylococcus aureus oxacillin resistant (MRSA) and Pseudomonas aeruginosa obtained from a patient with chronic wound infection were carried out using a standard Drip Flow Reactor (DFR) under conditions that mimic the flow of nutrients in the human skin. Anti-biofilm activity of chitosan gels and SSD showed a log-reduction of 6.0 for MRSA when chitosan gel with AgNPs at a concentration of 100 ppm was used, however it was necessary to increase the concentration of the chitosan gel with AgNPs to 1000 ppm to get a log-reduction of 3.3, while the SSD showed a total reduction of both bacteria in comparison with the negative control. The biocompatibility evaluation on primary fibroblasts showed better results when the chitosan gels with AgNPs were tested even in the high concentration, in contrast with SSD, which killed all the primary fibroblasts. In conclusion, chitosan gel formulations loaded with AgNPs effectively prevent the formation of biofilm and kill bacteria in established biofilm, which suggest that chitosan gels with AgNPs could be used for prevention and treatment of infections in chronic wounds. The statistic significance of the biocompatibility of chitosan gel formulations loaded with AgNPs represents an advance; however further research and development are necessary to translate this technology into therapeutic and

  6. Examination of the pharmacodynamics and pharmacokinetics of a diclofenac poly(lactic-co-glycolic) acid nanoparticle formulation in the rat.

    Science.gov (United States)

    Harirforoosh, S; West, K O; Murrell, D E; Denham, J W; Panus, P C; Hanley, G A

    2016-12-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are assembled into two categories; cyclooxygenase (COX-1) sparing inhibitors of COX-2 and non-selective NSAIDs. Diclofenac (DICLO) is a non-selective NSAID that has been linked to serious side effects including gastric ulcers and renal injury. In this study, we examine the effect of poly(lactic-co-glycolic) acid nanoformulation on DICLO-associated adverse events and pharmacokinetics using a nanoparticle (NP) formulation previously developed in our laboratory. Rats were administered a single dose of methylcellulose (VEH), blank NP, DICLO (10 mg/kg), or a DICLO-NP suspension equivalent to the DICLO dose. Urinary and blood parameters were measured at baseline and following treatment. Duodenal and gastric prostaglandin E2 (PGE2) and duodenal myeloperoxidase (MPO) were collected to assess inflammation at 24 hrs post-treatment. The mean percent change from baseline in sodium excretion rate (µmol/min/100 g body weight) differed significantly from VEH in the NP (p < 0.0001), DICLO (p < 0.0001), and DICLO-NP (p = 0.0001) groups. The differences among groups did not reach significance for plasma sodium or potassium concentrations, potassium excretion rate, gastric PGE2, or intestinal biomarker concentrations. Regarding renal histopathology, DICLO produced considerably more necrosis compared to VEH; while DICLO-NP did not elicit notable differences from VEH. Our results suggest that over the duration and dosage examined, DICLO-NP may reduce renal necrosis without influencing other side effects or drug characteristics.

  7. Influence of the introduction of a solubility enhancer on the formulation of lipidic nanoparticles with improved drug loading rates.

    Science.gov (United States)

    Malzert-Fréon, A; Saint-Lorant, G; Hennequin, D; Gauduchon, P; Poulain, L; Rault, S

    2010-06-01

    The objective of the present paper is to develop lipidic nanoparticles (NP) able to encapsulate drugs presenting limited solubility in both water and lipids, with high loading rates, and without using organic solvents. In this goal, a solubility enhancer, a macrogolglyceride (Labrasol), was incorporated in a formulation process based on a low-energy phase inversion temperature method. From electrical conductivity through the temperature scans, it appears that presence of Labrasol does not prevent the phase inversion, and it takes part in the microemulsion structuring, probably of bicontinuous type. After screening pseudo-ternary diagrams, the feasibility of NP was established. From results of a partial least square analysis, it appears that these NP present a core-shell structure where Labrasol is well encapsulated and contributes to the formation of the oily liquid core of the NP. The diameter of the NP, assessed by dynamic light scattering, remains kinetically stable. These NP, smaller than 200 nm, spherical in shape as attested by cryo-transmission electron micrographs, are able to encapsulate a tripentone, a new anticancer agent, with drug loading rates up to 6.5% (w/w). So highly drug-loaded lipidic nanocarriers were developed without using the slightest organic solvent trace, and making it easily possible dose adjustment. Copyright 2010 Elsevier B.V. All rights reserved.

  8. Miconazole-loaded solid lipid nanoparticles: formulation and evaluation of a novel formula with high bioavailability and antifungal activity

    Science.gov (United States)

    Aljaeid, Bader Mubarak; Hosny, Khaled Mohamed

    2016-01-01

    Background and objective Miconazole is a broad-spectrum antifungal drug that has poor aqueous solubility (lipid nanoparticles (MN-SLNs) for oral administration to find an innovative way to alleviate the disadvantages associated with commercially available capsules. Methods MN-SLNs were prepared by hot homogenization/ultrasonication. The solubility of miconazole in different solid lipids was measured. The effect of process variables, such as surfactant types, homogenization and ultrasonication times, and the charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release, antifungal activity against Candida albicans, and in vivo pharmacokinetics were studied in rabbits. Results The MN-SLN, consisting of 1.5% miconazole, 2% Precirol ATO5, 2.5% Cremophor RH40, 0.5% Lecinol, and 0.1% Dicetylphosphate, had an average diameter of 23 nm with a 90.2% entrapment efficiency. Furthermore, the formulation of MN-SLNs enhanced the antifungal activity compared with miconazole capsules. An in vivo pharmacokinetic study revealed that the bioavailability was enhanced by >2.5-fold. Conclusion MN-SLN was more efficient in the treatment of candidiasis with enhanced oral bioavailability and could be a promising carrier for the oral delivery of miconazole. PMID:26869787

  9. Formulation, optimization and characterization of cationic polymeric nanoparticles of mast cell stabilizing agent using the Box-Behnken experimental design.

    Science.gov (United States)

    Gajra, Balaram; Patel, Ravi R; Dalwadi, Chintan

    2016-01-01

    The present research work was intended to develop and optimize sustained release of biodegradable chitosan nanoparticles (CSNPs) as delivery vehicle for sodium cromoglicate (SCG) using the circumscribed Box-Behnken experimental design (BBD) and evaluate its potential for oral permeability enhancement. The 3-factor, 3-level BBD was employed to investigate the combined influence of formulation variables on particle size and entrapment efficiency (%EE) of SCG-CSNPs prepared by ionic gelation method. The generated polynomial equation was validated and desirability function was utilized for optimization. Optimized SCG-CSNPs were evaluated for physicochemical, morphological, in-vitro characterizations and permeability enhancement potential by ex-vivo and uptake study using CLSM. SCG-CSNPs exhibited particle size of 200.4 ± 4.06 nm and %EE of 62.68 ± 2.4% with unimodal size distribution having cationic, spherical, smooth surface. Physicochemical and in-vitro characterization revealed existence of SCG in amorphous form inside CSNPs without interaction and showed sustained release profile. Ex-vivo and uptake study showed the permeability enhancement potential of CSNPs. The developed SCG-CSNPs can be considered as promising delivery strategy with respect to improved permeability and sustained drug release, proving importance of CSNPs as potential oral delivery system for treatment of allergic rhinitis. Hence, further studies should be performed for establishing the pharmacokinetic potential of the CSNPs.

  10. Design and syntheses of MMP inhibitors and photosensitive lipid nanoparticle formulations for drug delivery

    Science.gov (United States)

    Subramaniam, Rajesh

    Drug administration without any compromise to the quality of life and lifespan is the ideal goal for disease management. The molecular mechanisms of several pathologies have shown that site-specific delivery of target-specific drugs seems to be a promising avenue to achieve this goal. This thesis describes the initial steps that we have taken toward that goal. Matrix metalloproteinases (MMPs) are a family of about 23 isozymes in humans that were actively targeted for treating a multitude of pathologies. Clinical studies carried out on cancer patients have revealed the complexity of the working of this enzyme family and necessitated the development of isozyme-specific MMP inhibitors. Our studies toward the development of isozyme-specific inhibitors have resulted in the development of several inhibitors that seem to be selective toward some MMP isozymes. Our understanding on the molecular mechanism that confers this selectivity is documented in this thesis. Another aspect of discussion in the thesis is the development of photosensitive liposomes for drug delivery that could be triggered to release the drug by irradiation with light of appropriate wavelength. Development of such delivery vehicles, in principle, would confer external spatiotemporal control on drug delivery. This could potentially lead to better disease management by minimizing side effects and enhancing patient compatibility. The thesis discusses our attempts toward the development of photosensitive liposomes. These liposomes incorporated a photosensitive lipid (PSL) that would be cleaved upon irradiation with UV light, causing liposomal destabilization and release of the enclosed drug. The discussion includes: (i) the syntheses of the PSLs, (ii) formulation of the photosensitive liposomes that contained a model drug, (iii) light-mediated release of the drug and (iv) the mechanism of photocleavage of the PSL that leads to content release from liposomes. The thesis concludes with suggestions toward the

  11. Immunological effects of iron oxide nanoparticles and iron-based complex drug formulations: Therapeutic benefits, toxicity, mechanistic insights, and translational considerations.

    Science.gov (United States)

    Shah, Ankit; Dobrovolskaia, Marina A

    2018-04-01

    Nanotechnology offers several advantages for drug delivery. However, there is the need for addressing potential safety concerns regarding the adverse health effects of these unique materials. Some such effects may occur due to undesirable interactions between nanoparticles and the immune system, and they may include hypersensitivity reactions, immunosuppression, and immunostimulation. While strategies, models, and approaches for studying the immunological safety of various engineered nanoparticles, including metal oxides, have been covered in the current literature, little attention has been given to the interactions between iron oxide-based nanomaterials and various components of the immune system. Here we provide a comprehensive review of studies investigating the effects of iron oxides and iron-based nanoparticles on various types of immune cells, highlight current gaps in the understanding of the structure-activity relationships of these materials, and propose a framework for capturing their immunotoxicity to streamline comparative studies between various types of iron-based formulations. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Development, in vitro and in vivo characterization of zoledronic acid functionalized hydroxyapatite nanoparticle based formulation for treatment of osteoporosis in animal model.

    Science.gov (United States)

    Khajuria, Deepak Kumar; Razdan, Rema; Mahapatra, Debiprosad Roy

    2015-01-23

    We investigated the potential of using novel zoledronic acid (ZOL)-hydroxyapatite (HA) nanoparticle based drug formulation in a rat model of postmenopausal osteoporosis. By a classical adsorption method, nanoparticles of HA loaded with ZOL (HNLZ) drug formulation with a size range of 100-130nm were prepared. 56 female Wistar rats were ovariectomized (OVX) or sham-operated at 3months of age. Twelve weeks post surgery, rats were randomized into seven groups and treated with various doses of HNLZ (100, 50 and 25μg/kg, intravenous single dose), ZOL (100μg/kg, intravenous single dose) and HA nanoparticle (100μg/kg, intravenous single dose). Untreated OVX and sham OVX served as controls. After three months treatment period, we evaluated the mechanical properties of the lumbar vertebra and femoral mid-shaft. Femurs were also tested for trabecular microarchitecture. Sensitive biochemical markers of bone formation and bone resorption in serum were also determined. With respect to improvement in the mechanical strength of the lumbar spine and the femoral mid-shaft, the therapy with HNLZ drug formulation was more effective than ZOL therapy in OVX rats. Moreover, HNLZ drug therapy preserved the trabecular microarchitecture better than ZOL therapy in OVX rats. Furthermore, the HNLZ drug formulation corrected increase in serum levels of bone-specific alkaline phosphatase, procollagen type I N-terminal propeptide, osteocalcin, tartrate-resistant acid phosphatase 5b and C-telopeptide of type 1 collagen better than ZOL therapy in OVX rats. The results strongly suggest that HNLZ novel drug formulation appears to be more effective approach for treating severe osteoporosis in humans. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Influence of the Formulation Parameters on the Particle Size and Encapsulation Efficiency of Resveratrol in PLA and PLA-PEG Blend Nanoparticles: A Factorial Design.

    Science.gov (United States)

    Lindner, Gabriela da Rocha; Dalmolin, Luciana Facco; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2015-12-01

    Polymeric nanoparticles are colloidal systems that promote protection and modification of physicochemical characteristics of a drug and that also ensure controlled and extended drug release. This paper reports a 2(3) factorial design study to optimize poly(lactide) (PLA) and poly(lactide)-polyethylene glycol (PLA-PEG) blend nanoparticles containing resveratrol (RVT) for prolonged release. The independent variables analyzed were solvent composition, surfactant concentration and ratio of aqueous to organic phase (two levels each factor). Mean particle size and RVT encapsulation efficiency were set as the dependent variables. The selected optimized parameters were set as organic phase comprised of a mixture of dichloromethane and ethyl acetate, 1% of surfactant polyvinyl alcohol and a 3:1 ratio of aqueous to organic phase, for both PLA and PLA-PEG blend nanoparticles. This formulation originated nanoparticles with size of 228 ± 10 nm and 185 ± 70 nm and RVT encapsulation efficiency of 82 ± 10% and 76 ± 7% for PLA and PLA-PEG blend nanoparticles, respectively. The in vitro release study showed a biphasic pattern with prolonged RVT release and PEG did not influence the RVT release. The in vitro release data were in favor of Higuchi-diffusion kinetics for both nanoformulations and the Kossmeyer-Peppas coefficient indicated that anomalous transport was the main release mechanism of RVT. PLA and PLA-PEG blend nanoparticles produced with single emulsion-solvent evaporation technology were found to be a promising approach for the incorporation of RVT and promoted its controlled release. The factorial design is a tool of great value in choosing formulations with optimized parameters.

  14. Influence of diblock copolymer PCL-mPEG and of various iodinated oils on the formulation by the emulsion-solvent diffusion process of radiopaque polymeric nanoparticles.

    Science.gov (United States)

    Hallouard, François; Briançon, Stéphanie; Anton, Nicolas; Li, Xiang; Vandamme, Thierry; Fessi, Hatem

    2013-11-01

    This pioneer study in the domain of blood pool contrast media formulation presents the influence of poly-ɛ-caprolactone-monomethoxy poly(ethylene glycol) (PCL-mPEG) and oils on the formulation of polymeric nanoparticles by emulsion-solvent diffusion. The nature of the oil used had no influence on the encapsulation rate, even if particles were formulated with a mix of PCL/PCL-mPEG. It did, however, influence the particle size and polydispersity, with macroglycerides appearing to be the lipid structure best suited to obtain the smallest monodisperse particles. When we used PCL-mPEG to form a PEG-hydrated layer to surround the nanoparticles, its tension active property had a favorable effect on particle size and polydispersity. We also showed the strong deleterious effect on particle size and polydispersity when the polymer proportion was increased to over 1% (w/v) in the pre-emulsion organic phase. Conversely, increasing the oil proportion in this organic phase simply resulted in a slight to insignificant deleterious effect on size and polydispersity, enabling the oil proportion to be enhanced up to 3% (w/v). Finally, we showed the favorable combined effect of oil iodination and the presence of PCL-mPEG on particles formulated by emulsion-solvent diffusion leading to the preparation of smaller polymeric iodine-containing particles. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  15. Synthesis and Characterization of Silicate Ester Prodrugs and Poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) Block Copolymers for Formulation into Prodrug-Loaded Nanoparticles

    Science.gov (United States)

    Wohl, Adam Richard

    Fine control of the physical and chemical properties of customized materials is a field that is rapidly advancing. This is especially critical in pursuits to develop and optimize novel nanoparticle drug delivery. Specifically, I aim to apply chemistry concepts to test the hypothesis "Silicate ester prodrugs of paclitaxel, customized to have the proper hydrophobicity and hydrolytic lability, can be formulated with well-defined, biocompatible, amphiphilic block copolymers into nanoparticles that are effective drugs." Chapter 1 briefly describes the context and motivation of the scientific pursuits described in this thesis. In Chapter 2, a family of model silicate esters is synthesized, the hydrolysis rate of each compound is benchmarked, and trends are established based upon the steric bulk and leaving group ability of the silicate substituents. These trends are then applied to the synthesis of labile silicate ester prodrugs in Chapter 3. The bulk of this chapter focuses on the synthesis, hydrolysis, and cytotoxicity of prodrugs based on paclitaxel, a widely used chemotherapeutic agent. In Chapter 4, a new methodology for the synthesis of narrowly dispersed, "random" poly(lactic-co-glycolic acid) polymers by a constant infusion of the glycolide monomer is detailed. Using poly(ethylene glycol) as a macroinitiator, amphiphilic block copolymers were synthesized. Co-formulating a paclitaxel silicate and an amphiphilic block copolymer via flash nanoprecipitation led to highly prodrug-loaded, kinetically trapped nanoparticles. Studies to determine the structure, morphology, behavior, and efficacy of these nanoparticles are described in Chapter 5. Efforts to develop a general strategy for the selective end-functionalization of the polyether block of these amphiphilic block copolymers are discussed in Chapter 6. Examples of this strategy include functionalization of the polyether with an azide or a maleimide. Finally, Chapter 7 provides an outlook for future development of

  16. Biosynthesis of zinc oxide nanoparticles by petals extract ofRosa indicaL., its formulation as nail paint and evaluation of antifungal activity against fungi causing onychomycosis.

    Science.gov (United States)

    Tiwari, Nikita; Pandit, Raksha; Gaikwad, Swapnil; Gade, Aniket; Rai, Mahendra

    2017-03-01

    Aim : The authors report the biological synthesis of zinc oxide nanoparticles (ZnO-NPs) from the petals extract of Rosa indica L. (rose). Its efficacy was evaluated against two dermatophytes: namely: Trichophyton mentagrophytes and Microsporum canis which cause onychomycosis. The activity of antibiotics against the tested dermatophytes was enhanced, when evaluated in combination with ZnO-NPs. Methods and results: The synthesised ZnO-NPs were preliminary detected by using ultraviolet UV visible spectroscopy, which showed specific absorbance. The ZnO-NPs were further characterised by nanoparticle tracking analysis (NTA), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffraction and Zetasizer. Moreover, nanoparticles containing nail paint (nanopaint) was formulated and its antifungal activity was also assessed against T. mentagrophytes and M. canis . ZnO-NPs and formulated nanopaint containing ZnO-NPs, both showed significant antifungal activity. The maximum activity was noted against M. canis and lesser against T. mentagrophytes. Minimum inhibitory concentration of ZnO-NPs was also determined against the dermatophytes causing onychomycosis infection. Conclusion: ZnO-NPs can be utilised as a potential antifungal agent for the treatment of onychomycosis after more experimental trials.

  17. Ultrafine PEG-coated poly(lactic-co-glycolic acid) nanoparticles formulated by hydrophobic surfactant-assisted one-pot synthesis for biomedical applications.

    Science.gov (United States)

    Chu, Chih-Hang; Wang, Yu-Chao; Huang, Hsin-Ying; Wu, Li-Chen; Yang, Chung-Shi

    2011-05-06

    A novel method was developed for the one-pot synthesis of ultrafine poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs), using an emulsion solvent evaporation formulation method. Using either cetyltrimethylammonium bromide (CTAB) or poly(ethylene glycol)-distearyl phosphoethanolamine (PEGPE) as an oily emulsifier during the emulsion process, produced PLGA particle sizes of less than 50 nm, constituting a breakthrough in emulsion formulation methods. The yield of ultrafine PLGA NPs increased with PEGPE/PLGA ratio, reaching a plateau at around 85%, when the PEGPE/PLGA ratio reached 3:1. The PEGPE-PLGA NPs exhibited high drug loading content, reduced burst release, good serum stability, and enhanced cell uptake rate compared with traditional PLGA NPs. Sub-50 nm diameter PEG-coated ultrafine PLGA NPs show great potential for in vivo drug delivery systems.

  18. Dataset for acrylate/silica nanoparticles formulations and photocured composites : Viscosity, filler dispersion and bulk Poisson׳s ratio

    NARCIS (Netherlands)

    Gojzewski, Hubert; Sadej, Mariola; Andrzejewska, Ewa; Kokowska, Martyna

    2017-01-01

    UV-curable polymer composites are of importance in industry, biomedical applications, scientific fields, and daily life. Outstanding physical properties of polymer composites were achieved with nanoparticles as filler, primarily in enhancing mechanical strength or barrier properties.

  19. Minimal-length Synthetic shRNAs Formulated with Lipid Nanoparticles are Potent Inhibitors of Hepatitis C Virus IRES-linked Gene Expression in Mice

    Directory of Open Access Journals (Sweden)

    Anne Dallas

    2013-01-01

    Full Text Available We previously identified short synthetic shRNAs (sshRNAs that target a conserved hepatitis C virus (HCV sequence within the internal ribosome entry site (IRES of HCV and potently inhibit HCV IRES-linked gene expression. To assess in vivo liver delivery and activity, the HCV-directed sshRNA, SG220 was formulated into lipid nanoparticles (LNP and injected i.v. into mice whose livers supported stable HCV IRES-luciferase expression from a liver-specific promoter. After a single injection, RNase protection assays for the sshRNA and 3H labeling of a lipid component of the nanoparticles showed efficient liver uptake of both components and long-lasting survival of a significant fraction of the sshRNA in the liver. In vivo imaging showed a dose-dependent inhibition of luciferase expression (>90% 1 day after injection of 2.5 mg/kg sshRNA with t1/2 for recovery of about 3 weeks. These results demonstrate the ability of moderate levels of i.v.-injected, LNP-formulated sshRNAs to be taken up by liver hepatocytes at a level sufficient to substantially suppress gene expression. Suppression is rapid and durable, suggesting that sshRNAs may have promise as therapeutic agents for liver indications.

  20. Synthesis and formulation of methotrexate (MTX) conjugated LaF3:Tb(3+)/chitosan nanoparticles for targeted drug delivery applications.

    Science.gov (United States)

    Mangaiyarkarasi, Rajendiran; Chinnathambi, Shanmugavel; Aruna, Prakasarao; Ganesan, Singaravelu

    2015-02-01

    Chitosan functionalized luminescent rare earth doped terbium nanoparticles (LaF3:Tb(3+)/chi NPs) as a drug carrier for methotrexate (MTX) was designed using a simple chemical precipitation method. The synthesized chitosan functionalized nanoparticles were found to be spherical in shape with an average diameter of 10-12nm. They are water soluble and biocompatible, in which the hydroxyl and amino functional groups on its surface are utilized for the bioconjugation of the anticancer drug, the methotrexate. The nature of MTX binding with LaF3:Tb(3+)/chi nanoparticles were examined using X-ray diffraction, zeta potential analyzer and transmission electron microscopy. The other interactions due to complex formation between MTX and LaF3:Tb(3+)/chi NPs were carried out by UV-Visible, steady and excited state fluorescence spectroscopy. The photo-physical characterization revealed that the adsorption and release of MTX from LaF3:Tb(3+)/chi NPs is faster than gold nanoparticles and also confirms that this may be due to weak interaction i.e. the Vander Waals force of attraction between the carboxyl and amino group of drug and nanoparticles. The maximum percentage yield and entrapment efficiency of 85.91±0.71 and 83.82± 0.14 were achieved at a stochiometric ratio of 4:5 of MTX and LaF3:Tb(3+)/chi nanoparticles respectively. In addition, antitumoral activity study reveals that MTX conjugated LaF3:Tb(3+)/chi nanoparticles show higher cytotoxic effect on MCF-7 breast cancer cell lines than that of free MTX. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. pH-responsive artemisinin derivatives and lipid nanoparticle formulations inhibit growth of breast cancer cells in vitro and induce down-regulation of HER family members.

    Directory of Open Access Journals (Sweden)

    Yitong J Zhang

    Full Text Available Artemisinin (ART dimers show potent anti-proliferative activities against breast cancer cells. To facilitate their clinical development, novel pH-responsive artemisinin dimers were synthesized for liposomal nanoparticle formulations. A new ART dimer was designed to become increasingly water-soluble as pH declines. The new artemisinin dimer piperazine derivatives (ADPs remained tightly associated with liposomal nanoparticles (NPs at neutral pH but were efficiently released at acidic pH's that are known to exist within solid tumors and organelles such as endosomes and lysosomes. ADPs incorporated into nanoparticles down regulated the anti-apoptotic protein, survivin, and cyclin D1 when incubated at low concentrations with breast cancer cell lines. We demonstrate for the first time, for any ART derivative, that ADP NPs can down regulate the oncogenic protein HER2, and its counterpart, HER3 in a HER2+ cell line. We also show that the wild type epidermal growth factor receptor (EGFR or HER1 declines in a triple negative breast cancer (TNBC cell line in response to ADP NPs. The declines in these proteins are achieved at concentrations of NP109 at or below 1 µM. Furthermore, the new artemisinin derivatives showed improved cell-proliferation inhibition effects compared to known dimer derivatives.

  2. Formulation and optimization of a novel oral fast dissolving film containing drug nanoparticles by Box-Behnken design-response surface methodology.

    Science.gov (United States)

    Shen, Chengying; Shen, Baode; Xu, He; Bai, Jinxia; Dai, Ling; Lv, Qingyuan; Han, Jin; Yuan, Hailong

    2014-05-01

    The purpose of this study was to design and optimize a novel drug nanoparticles-loaded oral fast dissolving film (NP-OFDF) using Box-Behnken design-response surface methodology. Drug nanosuspensions produced from high pressure homogenization were transformed into oral fast dissolving film containing drug nanoparticles by casting methods. Herpetrione (HPE), a novel and potent antiviral agent with poor water solubility that was extracted from Herpetospermum caudigerum, was studied as the model drug. The formulations of oral fast dissolving film containing HPE nanoparticles (HPE-NP-OFDF) were optimized by employing Box-Behnken design-response surface methodology and then systematically characterized. The optimized HPE-NP-OFDF was disintegrated in water within 20 s with reconstituted nanosuspensions particle size of 299.31 nm. Scanning electron microscopy (SEM) images showed that well-dispersed HPE nanoparticles with slight adhesion to each other were exposed on the surface of film or embedded in film. The X-ray diffractogram (XRD) analysis suggested that HPE in the HPE-NP-OFDF was in the amorphous state. In-vitro release study, approximate 77.23% of HPE was released from the HPE-NP-OFDF within 5 min, which was more than eight times compared with that of HPE raw materials (9.57%). The optimized HPE-NP-OFDF exhibits much faster drug release rates compared to HPE raw material, which indicated that this novel NP-OFDF may provide a potential opportunity for oral delivery of drugs with poor water solubility.

  3. Synthetic long peptide-based vaccine formulations for induction of cell mediated immunity: A comparative study of cationic liposomes and PLGA nanoparticles.

    Science.gov (United States)

    Varypataki, Eleni Maria; Silva, Ana Luisa; Barnier-Quer, Christophe; Collin, Nicolas; Ossendorp, Ferry; Jiskoot, Wim

    2016-03-28

    Nanoparticulate formulations for synthetic long peptide (SLP)-cancer vaccines as alternative to clinically used Montanide ISA 51- and squalene-based emulsions are investigated in this study. SLPs were loaded into TLR ligand-adjuvanted cationic liposomes and PLGA nanoparticles (NPs) to potentially induce cell-mediated immune responses. The liposomal and PLGA NP formulations were successfully loaded with up to four different compounds and were able to enhance antigen uptake by dendritic cells (DCs) and subsequent activation of T cells in vitro. Subcutaneous vaccination of mice with the different formulations showed that the SLP-loaded cationic liposomes were the most efficient for the induction of functional antigen-T cells in vivo, followed by PLGA NPs which were as potent as or even more than the Montanide and squalene emulsions. Moreover, after transfer of antigen-specific target cells in immunized mice, liposomes induced the highest in vivo killing capacity. These findings, considering also the inadequate safety profile of the currently clinically used adjuvant Montanide ISA-51, make these two particulate, biodegradable delivery systems promising candidates as delivery platforms for SLP-based immunotherapy of cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Prevention of colorectal cancer liver metastasis by exploiting liver immunity via chitosan-TPP/nanoparticles formulated with IL-12.

    Science.gov (United States)

    Xu, Qiongming; Guo, Lingchuan; Gu, Xinhua; Zhang, Biao; Hu, Xin; Zhang, Jiajia; Chen, Jinghong; Wang, Yi; Chen, Cheng; Gao, Bei; Kuang, Yuting; Wang, Shouli

    2012-05-01

    The development of effective therapies for the prevention of colorectal cancer (CRC) liver metastasis is of great importance. Recently, chitosan (CS) nanoparticles have been utilized as carriers of interluekin-12 (IL-12) administered locally to deliver therapeutic proteins and genes. In this study, we encapsulated IL-12 by incorporation using tripolyphosphate (TPP) as the coacervated crosslinking agent to form CS-TPP/IL-12 nanoparticles. We further characterized the association efficiency, rate of release, liver-targeting, and toxicity, which were predominantly dependent on the factors of particle size, zeta potential, pH of solution, and whether or not modified with TPP. Systemic delivery of CS-TPP/IL-12 nanoparticles significantly reduced the number and volume of CRC liver metastasis foci compared to the CS-TPP treated mouse group. Although delivery of IL-12 alone also inhibited the number of CRC liver metastasis observed, further study of the change in hepatic metastasis volume demonstrated no significant differences between the groups treated with CS-TPP or IL-12 alone. Mechanistically, CS-TPP nanoparticles blocked the toxicity of IL-12 and induced infiltration of NK cells and some T cells, which are most likely the effector cells that mediate tumor metastasis inhibition during CS-TPP/IL-12 immunotherapy. The results obtained from this study demonstrate the potential benefit of using chitosan modification technology as a cytokine delivery system for the successful prevention of CRC liver metastasis by exploiting liver immunity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. (BDMCA) Nanoparticles

    African Journals Online (AJOL)

    Methods: Nanoparticle formulations were fabricated by a double emulsion solvent evaporation technique using polycaprolactone as the polymer. The nanoparticles were characterised for drug content, particles size, in vitro drug release and the drug-polymer interaction. The in vivo properties of the formulations in male ...

  6. Panthenol-stabilized cerium dioxide nanoparticles for cosmeceutic formulations against ROS-induced and UV-induced damage.

    Science.gov (United States)

    Zholobak, N M; Shcherbakov, A B; Bogorad-Kobelska, A S; Ivanova, O S; Baranchikov, A Ye; Spivak, N Ya; Ivanov, V K

    2014-01-05

    A method of panthenol-stabilized cerium dioxide nanoparticles synthesis was developed and their effect on the survival rate of human epidermoid cancer cells HEp-2 and diploid epithelial swine testicular cell line (ST-cells) under oxidative stress conditions induced by hydrogen peroxide introduction and UV irradiation was studied. The results obtained indicate that the use of panthenol as a stabilizer supposedly provides a substantial increase in the efficiency of protection. The degree of protection is determined by panthenol-to-ceria molar ratio. The combination of panthenol and nano-ceria protects biological objects under study from reactive oxygen species (ROS) and UV-irradiation more effectively than individual panthenol or ceria. The protective action of panthenol-stabilized cerium dioxide nanoparticles depends strongly on their composition and the means of their application. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Immunisation of Sheep with Bovine Viral Diarrhoea Virus, E2 Protein Using a Freeze-Dried Hollow Silica Mesoporous Nanoparticle Formulation.

    Directory of Open Access Journals (Sweden)

    Donna Mahony

    Full Text Available Bovine viral diarrhoea virus 1 (BVDV-1 is arguably the most important viral disease of cattle. It is associated with reproductive, respiratory and chronic diseases in cattle across the world. In this study we have investigated the capacity of the major immunological determinant of BVDV-1, the E2 protein combined with hollow type mesoporous silica nanoparticles with surface amino functionalisation (HMSA, to stimulate immune responses in sheep. The current work also investigated the immunogenicity of the E2 nanoformulation before and after freeze-drying processes. The optimal excipient formulation for freeze-drying of the E2 nanoformulation was determined to be 5% trehalose and 1% glycine. This excipient formulation preserved both the E2 protein integrity and HMSA particle structure. Sheep were immunised three times at three week intervals by subcutaneous injection with 500 μg E2 adsorbed to 6.2 mg HMSA as either a non-freeze-dried or freeze-dried nanoformulation. The capacity of both nanovaccine formulations to generate humoral (antibody and cell-mediated responses in sheep were compared to the responses in sheep immunisation with Opti-E2 (500 μg together with the conventional adjuvant Quil-A (1 mg, a saponin from the Molina tree (Quillaja saponira. The level of the antibody responses detected to both the non-freeze-dried and freeze-dried Opti-E2/HMSA nanoformulations were similar to those obtained for Opti-E2 plus Quil-A, demonstrating the E2 nanoformulations were immunogenic in a large animal, and freeze-drying did not affect the immunogenicity of the E2 antigen. Importantly, it was demonstrated that the long term cell-mediated immune responses were detectable up to four months after immunisation. The cell-mediated immune responses were consistently high in all sheep immunised with the freeze-dried Opti-E2/HMSA nanovaccine formulation (>2,290 SFU/million cells compared to the non-freeze-dried nanovaccine formulation (213-500 SFU/million cells

  8. Polymeric nanoparticles for co-delivery of synthetic long peptide antigen and poly IC as therapeutic cancer vaccine formulation

    NARCIS (Netherlands)

    Rahimian, Sima; Fransen, Marieke F.; Kleinovink, Jan Willem; Christensen, Jonatan Riis; Amidi, Maryam|info:eu-repo/dai/nl/304834912; Hennink, Wim E.|info:eu-repo/dai/nl/070880409; Ossendorp, Ferry

    2015-01-01

    The aim of the current study was to develop a cancer vaccine formulation for treatment of human papillomavirus (HPV)-induced malignancies. Synthetic long peptides (SLPs) derived from HPV16 E6 and E7 oncoproteins have been used for therapeutic vaccination in clinical trials with promising results. In

  9. Biocompatibility and antibacterial activity of nitrogen-doped titanium dioxide nanoparticles for use in dental resin formulations.

    Science.gov (United States)

    Zane, Andrew; Zuo, Ranfang; Villamena, Frederick A; Rockenbauer, Antal; Digeorge Foushee, Ann Marie; Flores, Kristin; Dutta, Prabir K; Nagy, Amber

    The addition of antibacterial functionality to dental resins presents an opportunity to extend their useful lifetime by reducing secondary caries caused by bacterial recolonization. In this study, the potential efficacy of nitrogen-doped titanium dioxide nanoparticles for this purpose was determined. Nitrogen doping was carried out to extend the ultraviolet absorbance into longer wavelength blue light for increased biocompatibility. Titanium dioxide nanoparticles (approximately 20-30 nm) were synthesized with and without nitrogen doping using a sol-gel method. Ultraviolet-Visible spectroscopy indicated a band of trap states, with increasing blue light absorbance as the concentration of the nitrogen dopant increased. Electron paramagnetic resonance measurements indicated the formation of superoxide and hydroxyl radicals upon particle exposure to visible light and oxygen. The particles were significantly toxic to Escherichia coli in a dose-dependent manner after a 1-hour exposure to a blue light source (480 nm). Intracellular reactive oxygen species assay demonstrated that the particles caused a stress response in human gingival epithelial cells when exposed to 1 hour of blue light, though this did not result in detectable release of cytokines. No decrease in cell viability was observed by water-soluble tetrazolium dye assay. The results show that nitrogen-doped titanium dioxide nanoparticles have antibacterial activity when exposed to blue light, and are biocompatible at these concentrations.

  10. Formulation and Cytotoxicity of Ribosome-Inactivating Protein Mirabilis Jalapa L. Nanoparticles Using Alginate-Low Viscosity Chitosan Conjugated with Anti-Epcam Antibodies in the T47D Breast Cancer Cell Line.

    Science.gov (United States)

    Wicaksono, Psycha Anindya; Name, Sismindari; Martien, Ronny; Ismail, Hilda

    2016-01-01

    Ribosome-inactivating protein (RIP) from Mirabilis jalapa L. leaves has cytotoxic effects on breast cancer cell lines but is less toxic towards normal cells. However, it can easily be degraded after administration so it needs to be formulated into nanoparticles to increase its resistance to enzymatic degradation. The objectives of this study were to develop a protein extract of M. jalapa L. leaves (RIP-MJ) incorporated into nanoparticles conjugated with Anti-EpCAM antibodies, and to determine its cytotoxicity and selectivity in the T47D breast cancer cell line. RIP-MJ was extracted from red-flowered M. jalapa L. leaves. Nanoparticles were formulated based on polyelectrolyte complexation using low viscosity chitosan and alginate, then chemically conjugated with anti-EpCAM antibody using EDAC based on carbodiimide reaction. RIP-MJ nanoparticles were characterised for the particle size, polydispersity index, zeta potential, particle morphology, and entrapment efficiency. The cytotoxicity of RIP-MJ nanoparticles against T47D and Vero cells was then determined with MTT assay. The optimal formula of RIP-MJ nanoparticles was obtained at the concentration of RIP-MJ, low viscosity chitosan and alginate respectively 0.05%, 1%, and 0.4% (m/v). RIP-MJ nanoparticles are hexagonal with high entrapment efficiency of 98.6%, average size of 130.7 nm, polydispersity index of 0.380 and zeta potential +26.33 mV. The IC50 values of both anti-EpCAM-conjugated and non-conjugated RIP-MJ nanoparticles for T47D cells (13.3 and 14.9 μg/mL) were lower than for Vero cells (27.8 and 33.6 μg/mL). The IC50 values of conjugated and non- conjugated RIP-MJ for both cells were much lower than IC50 values of non-formulated RIP-MJ (>500 μg/mL).

  11. In vivo distribution of zoledronic acid in a bisphosphonate-metal complex-based nanoparticle formulation synthesized by a reverse microemulsion method.

    Science.gov (United States)

    Li, Xu; Naguib, Youssef W; Cui, Zhengrong

    2017-06-30

    Bisphosphonates are used to treat bone diseases such as osteoporosis and cancer-induced bone pain and fractures. It is thought that modifying the pharmacokinetics and biodistribution profiles of bisphosphonates (i.e. rapid renal clearance and extensive bone absorption) will not only reduce their side effects, but also expand their clinical applications to extraskeletal tissues. In the present work, using zoledronic acid (Zol) and calcium as model bisphosphonate and metal molecules, respectively, we prepared DOPA (an anionic lipid)-coated spherical Zol-Ca nanocomposites (Zol-Ca@DOPA) and developed Zol-nanoparticle formulations (i.e. Zol-Ca@bi-lipid NPs) based on the nanocomposites. The influence of the inputted weight ratio of Zol-Ca@DOPA to DSPE-PEG 2k on the properties (e.g. size, size distribution, loading efficiency, encapsulation efficiency, zeta potential, and polydispersity) of Zol-Ca@bi-lipid NPs was investigated, and a type of Zol-Ca@bi-lipid NPs with size around 25nm was selected for further studies. In a mouse model, the Zol-Ca@bi-lipid NPs significantly reduced the bone distribution of Zol, increased the blood circulating time of Zol, and altered the distribution of Zol in major organs, as compared to free Zol. It is expected that similar nanoparticles prepared with bisphosphonate-metal complexes can be explored to expand the applications to bisphosphonates in extraskeletal tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Development of a non-toxic and non-denaturing formulation process for encapsulation of SDF-1α into PLGA/PEG-PLGA nanoparticles to achieve sustained release.

    Science.gov (United States)

    Haji Mansor, Muhammad; Najberg, Mathie; Contini, Aurélien; Alvarez-Lorenzo, Carmen; Garcion, Emmanuel; Jérôme, Christine; Boury, Frank

    2018-04-01

    Chemokines are known to stimulate directed migration of cancer cells. Therefore, the strategy involving gradual chemokine release from polymeric vehicles for trapping cancer cells is of interest. In this work, the chemokine stromal cell-derived factor-1α (SDF-1α) was encapsulated into nanoparticles composed of poly-(lactic-co-glycolic acid) (PLGA) and a polyethylene glycol (PEG)-PLGA co-polymer to achieve sustained release. SDF-1α, and lysozyme as a model protein, were firstly precipitated to promote their stability upon encapsulation. A novel phase separation method utilising a non-toxic solvent in the form of isosorbide dimethyl ether was developed for the individual encapsulation of SDF-1α and lysozyme precipitates. Uniform nanoparticles of 200-250 nm in size with spherical morphologies were successfully synthesised under mild formulation conditions and conveniently freeze-dried in the presence of hydroxypropyl-β-cyclodextrin as a stabiliser. The effect of PLGA carboxylic acid terminal capping on protein encapsulation efficiency and release rate was also explored. Following optimisation, sustained release of SDF-1α was achieved over a period of 72 h. Importantly, the novel encapsulation process was found to induce negligible protein denaturation. The obtained SDF-1α nanocarriers may be subsequently incorporated within a hydrogel or other scaffolds to establish a chemokine concentration gradient for the trapping of glioblastoma cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Formulation and in vitro characterization of poly(dl-lactide-co-glycolide)/Eudragit RLPO or RS30D nanoparticles as an oral carrier of levofloxacin hemihydrate.

    Science.gov (United States)

    Hasan, Azza A; Sabry, Shereen A; Abdallah, Marwa H; El-Damasy, Dalia A

    2016-09-01

    The main objective of this study was to design positively charged Levofloxacin Hemihydrate (Levo-h)-loaded nanoparticles with improved entrapment efficiency and antibacterial activity. PLGA alone or in combinations with Eudragit® RLPO or RS30D with or without positively charged inducing agent; 1,2-dioleoyl-3-trimethylammonium-propane, chloride salt (DOTAP); were used for preparation of nanoparticles. Blending between PLGA and Eudragit® RLPO or RS30D with inclusion of DOTAP caused a marked increase in entrapment efficiency and switched zeta potential from negative to positive. Nanoparticle formulations; NR3 (Levo-h:PLGA:Eudragit® RLPO; 1:1:1 w/w with DOTAP) and NS3 (Levo-h:PLGA:Eudragit® RS30D; 1:1:1 w/w with DOTAP) that possess high positive zeta potential (59.3 ± 7.5 and 55.1 ± 8.2 mV, respectively) and Efficient Levo-h entrapment (89.54 ± 1.5 and 77.65 ± 1.8%, respectively) were selected for further examinations; in vitro release, physical stability and microbiological study. NR3 and NS3 showed significant sustained release of Levo-h. NR3 and NS3 exhibited good stability after storage at room temperature. Microbiological assay showed strengthened antibacterial activity of NR3 against both types of gram-negative bacteria (E. coli, Ps. aeruginosa) and of NS3 against Ps. aeruginosa compared to free Levo-h solution. NR3 and NS3 appear to be promising oral delivery system for Levo-h.

  14. Dry powder inhaler formulation of high-payload antibiotic nanoparticle complex intended for bronchiectasis therapy: Spray drying versus spray freeze drying preparation.

    Science.gov (United States)

    Yu, Hong; Teo, Jeanette; Chew, Jia Wei; Hadinoto, Kunn

    2016-02-29

    Inhaled nano-antibiotics have recently emerged as the promising bronchiectasis treatment attributed to the higher and more localized antibiotic exposure generated compared to native antibiotics. Antibiotic nanoparticle complex (or nanoplex in short) prepared by self-assembly complexation with polysaccharides addresses the major drawbacks of existing nano-antibiotics by virtue of its high payload and cost-effective preparation. Herein we developed carrier-free dry powder inhaler (DPI) formulations of ciprofloxacin nanoplex by spray drying (SD) and spray freeze drying (SFD). d-Mannitol and l-leucine were used as the drying adjuvant and aerosol dispersion enhancer, respectively. The DPI formulations were evaluated in vitro in terms of the (1) aerosolization efficiency, (2) aqueous reconstitution, (3) antibiotic release, and (4) antimicrobial activity against respiratory pathogen Pseudomonas aeruginosa. The SFD powders exhibited superior aerosolization efficiency to their SD counterparts in terms of emitted dose (92% versus 66%), fine particle fraction (29% versus 23%), and mass median aerodynamic diameter (3 μm versus 6 μm). The superior aerosolization efficiency of the SFD powders was attributed to their large and porous morphology and higher l-leucine content. While the SFD powders exhibited poorer aqueous reconstitution that might jeopardize their mucus penetrating ability, their antibiotic release profile and antimicrobial activity were not adversely affected. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. A novel formulation for controlled release of heparin-DOCA conjugate dispersed as nanoparticles in polyurethane film.

    Science.gov (United States)

    Moon, H T; Lee, Y K; Han, J K; Byu, Y

    2001-02-01

    Heparin is a potent anticoagulant agent that interacts strongly with antithrombin III to prevent the formation of fibrin clot. In this study, we propose a new method for preparing a heparin-releasing system using a simple solvent casting. The heparin-DOCA conjugate, having an amphiphilic property, was homogeneously mixed with polyurethane in the co-solvent of dioxane, propanol and water. After casting the film, heparin-DOCA was homogeneously dispersed as nanoparticles in a polyurethane film. As the loading amount of heparin-DOCA in the film was increased, nanoparticle size, water uptake, and release rate were increased. Moreover, the percentage of released amount of heparin-DOCA was increased with the increase in the loading amount of heparin-DOCA. This was because the size of heparin-DOCA particles increases with the increase in the loading amount of heparin-DOCA, thereby decreasing the distance between particles and the total diffusion length to the surface. The release rate of heparin-DOCA can be controlled by the amount of the drug being loaded and the film thickness. When the heparin-DOCA loaded on the polyurethane films was above 7.5%, the released heparin-DOCA prevented the formation of fibrin clot and the platelet adhesion on the film surface.

  16. Characterization of long-circulating cationic nanoparticle formulations consisting of a two-stage PEGylation step for the delivery of siRNA in a breast cancer tumor model.

    Science.gov (United States)

    Ho, Emmanuel A; Osooly, Maryam; Strutt, Dita; Masin, Dana; Yang, Youngjoo; Yan, Hong; Bally, Marcel

    2013-01-01

    Polyethylene glycol (PEG) has been used widely in liposomal formulations as a strategy to inhibit opsonization by plasma proteins and to prolong liposome plasma circulation time. PEG can be incorporated onto the surface of liposomes either during the spontaneous self-assembling process or inserted after vesicle formation. The advantages of employing the PEG postinsertion method include improved drug encapsulation efficiency and the ability to incorporate PEG conjugates for enhanced cell binding and uptake. In this study, we propose to evaluate a cationic lipid nanoparticle formulation containing two PEGylation steps: pre- and post-siRNA insertion. Our results indicate that formulations consisting of the extra PEG post-insertion step significantly increased siRNA circulation in the plasma by two-folds in comparison with the formulations consisting of only the single PEGylation step. Moreover, this formulation was able to efficiently carry siRNA to the tumor site, increase siRNA stability and significantly downregulate luciferase mRNA expression by >50% when compared with the controls in an intraperitoneal and subcutaneous breast cancer tumor model. Overall, our cationic lipid nanoparticle formulation displayed enhanced plasma circulation, reduced liver accumulation, enhanced tumor targeting, and effective gene knockdown--demonstrating excellent utility for the delivery of siRNA. Copyright © 2012 Wiley Periodicals, Inc.

  17. A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Bo [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Sun, Ding [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Department of Hepatobiliary Surgery, First Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Sun, Chao; Sun, Yun-Fan; Sun, Hai-Xiang [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Zhu, Qing-Feng [The Johns Hopkins University School of Medicine, Division of Gastrointestinal and Liver Pathology, Baltimore, MD, 21205 (United States); Institute of Biomedical Sciences, Fudan University, Shanghai, 200032 (China); Yang, Xin-Rong [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Gao, Ya-Bo [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032 (China); Tang, Wei-Guo [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Fan, Jia [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Institute of Biomedical Sciences, Fudan University, Shanghai, 200032 (China); Maitra, Anirban [The Sol Goldman Pancreatic Cancer Research Center, Departments of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205 (United States); and others

    2015-12-25

    Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root (Curcuma longa) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primary liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development. - Highlights: • Polymeric nanoparticle formulation of curcumin not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. • In combination with sorafenib, NanoCurcumin induced HCC cell apoptosis and cell cycle arrest. • NanoCurcumin and

  18. A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hu, Bo; Sun, Ding; Sun, Chao; Sun, Yun-Fan; Sun, Hai-Xiang; Zhu, Qing-Feng; Yang, Xin-Rong; Gao, Ya-Bo; Tang, Wei-Guo; Fan, Jia; Maitra, Anirban

    2015-01-01

    Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root (Curcuma longa) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primary liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development. - Highlights: • Polymeric nanoparticle formulation of curcumin not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. • In combination with sorafenib, NanoCurcumin induced HCC cell apoptosis and cell cycle arrest. • NanoCurcumin and

  19. Microwave-assisted formulation of solid lipid nanoparticles loaded with non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Shah, Rohan M; Eldridge, Daniel S; Palombo, Enzo A; Harding, Ian H

    2016-12-30

    Stearic acid-based solid lipid nanoparticles (SLNs) were prepared using the microwave assisted one-pot microemulsions procedure pioneered by our group. In this study, non-steroidal anti-inflammatory drugs (NSAIDs) including indomethacin, ketoprofen and nimesulide were selected as ideal "test" drugs, based on their poor water solubility. The model drugs were incorporated within the SLNs by the microwave-assisted procedure at the time of SLN production. The microwave-produced drug-loaded SLNs were evaluated in terms of their physicochemical characteristics, drug release behavior and their uptake into against A549 cell line (human lung epithelial cells). The microwave-produced drug-loaded SLNs had a small particle size distribution, negative zeta potential and high encapsulation efficiency. The drug release studies were consistent with a core-shell structure of SLNs (probably a drug-loaded shell) which results in biphasic drug release from the SLNs. The drug release kinetics suggested a good fit of the release data to the Makoid-Banakar model and was governed by Fickian diffusion. The drug-loaded SLNs showed concentration-dependent cytotoxicity and reduced IL-6 and IL-8 secretion in lipopolysaccharide-induced cells. All of the above findings suggest that the microwave-produced SLNs could be promising drug carriers of NSAIDs and will further facilitate their development for topical, oral and/or nasal administration. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Mechanical properties and antibiotic release characteristics of poly(methyl methacrylate)-based bone cement formulated with mesoporous silica nanoparticles.

    Science.gov (United States)

    Letchmanan, Kumaran; Shen, Shou-Cang; Ng, Wai Kiong; Kingshuk, Poddar; Shi, Zhilong; Wang, Wilson; Tan, Reginald B H

    2017-08-01

    The influence of mesoporous silica nanoparticles (MSNs) loaded with antibiotics on the mechanical properties of functional poly(methyl methacrylate)-(PMMA) based bone cements is investigated. The incorporation of MSNs to the bone cements (8.15wt%) shows no detrimental effects on the biomechanical properties of the freshly solidified bone cements. Importantly, there are no significant changes in the compression strength and bending modulus up to 6 months of aging in PBS buffer solution. The preserved mechanical properties of MSN-functionalized bone cements is attributed to the unchanged microstructures of the cements, as more than 96% of MSNs remains in the bone cement matrix to support the cement structures after 6 months of aging. In addition, the MSN-functionalized bone cements are able to increase the drug release of gentamicin (GTMC) significantly as compared with commercially available antibiotic-loaded bone cements. It can be attributed to the loaded nano-sized MSNs with uniform pore channels which build up an effective nano-network path enable the diffusion and extended release of GTMC. The combination of excellent mechanical properties and sustainable drug delivery efficiency demonstrates the potential applicability of MSN-functionalized PMMA bone cements for orthopedic surgery to prevent post-surgery infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Formulation and optimization of doxorubicin loaded polymeric nanoparticles using Box-Behnken design: ex-vivo stability and in-vitro activity.

    Science.gov (United States)

    Shaikh, Muhammad Vaseem; Kala, Manika; Nivsarkar, Manish

    2017-03-30

    Biodegradable nanoparticles (NPs) have gained tremendous interest for targeting chemotherapeutic drugs to the tumor environment. Inspite of several advances sufficient encapsulation along with the controlled release and desired size range have remained as considerable challenges. Hence, the present study examines the formulation optimization of doxorubicin loaded PLGA NPs (DOX-PLGA-NPs), prepared by single emulsion method for cancer targeting. Critical process parameters (CPP) were selected by initial screening. Later, Box-Behnken design (BBD) was used for analyzing the effect of the selected CPP on critical quality attributes (CQA) and to generate a design space. The optimized formulation was stabilized by lyophilization and was used for in-vitro drug release and in-vitro activity on A549 cell line. Moreover, colloidal stability of the NPs in the biological milieu was assessed. Amount of PLGA and PVA, oil:water ratio and sonication time were the selected independent factors for BBD. The statistical data showed that a quadratic model was fitted to the data obtained. Additionally, the lack of fit values for the models was not significant. The delivery system showed sustained release behavior over a period of 120h and was governed by Fickian diffusion. The multipoint analysis at 24, 48 and 72h showed gradual reduction in IC50 value of DOX-PLGA-NPs (p<0.05, Fig. 9). DOX-PLGA-NPs were found to be stable in the biological fluids indicating their in-vivo applicability. In conclusion, optimization of the DOX-PLGA-NPs by BBD yielded in a promising drug carrier for doxorubicin that could provide a novel treatment modality for cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Development of shampoo, soap and ointment formulated by green synthesised silver nanoparticles functionalised with antimicrobial plants oils in veterinary dermatology: treatment and prevention strategies.

    Science.gov (United States)

    Bansod, Sunita Dashrath; Bawaskar, Manisha Subrashrao; Gade, Aniket Krishnarao; Rai, Mahendra Kumar

    2015-08-01

    Many scientists have focused their research on the role of nanotechnology for the control of human pathogens, but there are also many topical pathogens present in animals, which infect animals and transfer to humans. Topical therapy is extremely important for the management of dermatological condition in animals. Therefore, the present study aims to evaluate the efficacy of biogenic silver nanoparticles (AgNPs) in combination with herbal oils against animal skin infections which may be responsible for causing infections in human beings. Here, the authors synthesised and characterised the AgNPs from Azadirachta indica. The oils were extracted from medicinal plants including Cymbopogon citratus, Cymbopogon martini, Eucalyptus globules, A. indica and Ocimum sanctum and the antifungal and antibacterial activity of plant oils along with AgNPs were evaluated. An excision wound model was used for the study of wound healing activity in rabbits. AgNPs functionalised oil has demonstrated remarkable antimicrobial activity against pathogens present on the skin of animals. The nano-functionalised antimicrobial oils were used in the formulation of shampoo, soap and ointment for veterinary dermatology. Antimicrobial products of plant origin with AgNPs are valuable, safe and have a specific role in controlling diseases. The authors believe that this approach will be a good alternative therapy to solve the continuous antibiotic resistance developed by many bacterial pathogens and will be utilised in various animal contacting areas in medicine.

  3. Hansen solubility parameters (HSP) for prescreening formulation of solid lipid nanoparticles (SLN): in vitro testing of curcumin-loaded SLN in MCF-7 and BT-474 cell lines.

    Science.gov (United States)

    Doktorovova, Slavomira; Souto, Eliana B; Silva, Amélia M

    2018-01-01

    Curcumin, a phenolic compound from turmeric rhizome (Curcuma longa), has many interesting pharmacological effects, but shows very low aqueous solubility. Consequently, several drug delivery systems based on polymeric and lipid raw materials have been proposed to increase its bioavailability. Solid lipid nanoparticles (SLN), consisting of solid lipid matrix and a surfactant layer can load poorly water-soluble drugs, such as curcumin, deliver them at defined rates and enhance their intracellular uptake. In the present work, we demonstrate that, despite the drug's affinity to lipids frequently used in SLN production, the curcumin amount loaded in most SLN formulations may be too low to exhibit anticancer properties. The predictive curcumin solubility in solid lipids has been thoroughly analyzed by Hansen solubility parameters, in parallel with the lipid-screening solubility tests for a range of selected lipids. We identified the most suitable lipid materials for curcumin-loaded SLN, producing physicochemically stable particles with high encapsulation efficiency (>90%). Loading capacity of curcumin in SLN allowed preventing the cellular damage caused by cationic SLN on MCF-7 and BT-474 cells but was not sufficient to exhibit drug's anticancer properties. But curcumin-loaded SLN exhibited antioxidant properties, substantiating the conclusions that curcumin's effect in cancer cells is highly dose dependent.

  4. Pharmacokinetics, tissue distribution, and metabolites of a polyvinylpyrrolidone-coated norcantharidin chitosan nanoparticle formulation in rats and mice, using LC-MS/MS

    Directory of Open Access Journals (Sweden)

    Ding XY

    2012-04-01

    Full Text Available Xin-Yuan Ding1, Cheng-Jiao Hong2, Yang Liu1, Zong-Lin Gu1, Kong-Lang Xing1, Ai-Jun Zhu1, Wei-Liang Chen1, Lin-Seng Shi1, Xue-Nong Zhang1, Qiang Zhang31Department of Pharmaceutics, College of Pharmaceutical science, Soochow University, Suzhou, 2Jiang Su Provincial Key Laboratory of Radiation Medicine and Protection, Suzhou, 3Department of Pharmaceutics, School of Pharmaceutical Science, Peking University, Beijing, People’s Republic of ChinaAbstract: A novel formulation containing polyvinylpyrrolidone (PVP K30-coated norcantharidin (NCTD chitosan nanoparticles (PVP–NCTD–NPs was prepared by ionic gelation between chitosan and sodium tripolyphosphate. The average particle size of the PVP–NCTD–NPs produced was 140.03 ± 6.23 nm; entrapment efficiency was 56.33% ± 1.41%; and drug-loading efficiency was 8.38% ± 0.56%. The surface morphology of NCTD nanoparticles (NPs coated with PVP K30 was characterized using various analytical techniques, including X-ray diffraction and atomic force microscopy. NCTD and its metabolites were analyzed using a sensitive and specific liquid chromatography-tandem mass spectrometry method with samples from mice and rats. The results indicated the importance of the PVP coating in controlling the shape and improving the entrapment efficiency of the NPs. Pharmacokinetic profiles of the NCTD group and PVP–NCTD–NP group, after oral and intravenous administration in rats, revealed that relative bioavailabilities were 173.3% and 325.5%, respectively. The elimination half-life increased, and there was an obvious decrease in clearance. The tissue distribution of NCTD in mice after the intravenous administration of both formulations was investigated. The drug was not quantifiable at 6 hours in all tissues except for the liver and kidneys. The distribution of the drug in the liver and bile was notably improved in the PVP–NCTD–NP group. The metabolites and excretion properties of NCTD were investigated by analyzing

  5. Nano composite system based on coumarin derivative–titanium dioxide nanoparticles and ionic liquid: Determination of levodopa and carbidopa in human serum and pharmaceutical formulations

    International Nuclear Information System (INIS)

    Mazloum-Ardakani, Mohammad; Khoshroo, Alireza

    2013-01-01

    Graphical abstract: -- Highlights: •Nanostructured electrochemical sensor based on TiO 2 and ionic liquid was used for the determination of levodopa in the presence of carbidopa. •Selectivity, reproducibility and low detection limit make the nanostructured modified electrode very useful for accurate determination of levodopa. •This sensor was applied in determination of levodopa and carbidopa in pharmaceutical formulations, blood serum and urine. -- Abstract: The combination of coumarin derivative (7-(1,3-dithiolan-2-yl)-9,10-dihydroxy-6H-benzofuro[3,2-c]chromen-6-on), (DC)–titanium dioxide nanoparticles (TiO 2 ) and ionic liquid (IL) yields nanostructured electrochemical sensor, formed a novel kind of structurally uniform and electrocatalytic activity material. This new ionic liquid–TiO 2 nanoparticles modified carbon paste electrode (IL–CTP) due to its enhanced conductivity presented very large current response from electroactive substrates. The modified electrode was characterized by different methods including a scanning electron microscope (SEM), electrochemical impedance spectroscopy (EIS) and voltammetry. A pair of well-defined quasi reversible redox peaks of coumarin derivative was obtained at the modified carbon paste electrode (DC/IL–CTP) by direct electron transfer between the coumarin derivative and the CP electrode. Dramatically enhanced electrocatalytic activity was exemplified at the DC/IL–CTP electrode, as an electrochemical sensor to study the electro oxidation of levodopa (LD) and carbidopa (CD). Based on differential pulse voltammetry (DPV), the oxidation of LD and CD exhibited the dynamic range between 0.10– 900.0 μM and 20.0–900.0 μM respectively, and the detection limit (3σ) for LD and CD were 41 nM and 0.38 μM, respectively. DPV was used for simultaneous determination of LD and CD at the DC/IL–CTP electrode, and quantitation of LD and CD in some real samples (such as tablets of Parkin-C Fort and Madopar, Sinemet

  6. Nano composite system based on coumarin derivative–titanium dioxide nanoparticles and ionic liquid: Determination of levodopa and carbidopa in human serum and pharmaceutical formulations

    Energy Technology Data Exchange (ETDEWEB)

    Mazloum-Ardakani, Mohammad, E-mail: mazloum@yazd.ac.ir; Khoshroo, Alireza

    2013-10-10

    Graphical abstract: -- Highlights: •Nanostructured electrochemical sensor based on TiO{sub 2} and ionic liquid was used for the determination of levodopa in the presence of carbidopa. •Selectivity, reproducibility and low detection limit make the nanostructured modified electrode very useful for accurate determination of levodopa. •This sensor was applied in determination of levodopa and carbidopa in pharmaceutical formulations, blood serum and urine. -- Abstract: The combination of coumarin derivative (7-(1,3-dithiolan-2-yl)-9,10-dihydroxy-6H-benzofuro[3,2-c]chromen-6-on), (DC)–titanium dioxide nanoparticles (TiO{sub 2}) and ionic liquid (IL) yields nanostructured electrochemical sensor, formed a novel kind of structurally uniform and electrocatalytic activity material. This new ionic liquid–TiO{sub 2} nanoparticles modified carbon paste electrode (IL–CTP) due to its enhanced conductivity presented very large current response from electroactive substrates. The modified electrode was characterized by different methods including a scanning electron microscope (SEM), electrochemical impedance spectroscopy (EIS) and voltammetry. A pair of well-defined quasi reversible redox peaks of coumarin derivative was obtained at the modified carbon paste electrode (DC/IL–CTP) by direct electron transfer between the coumarin derivative and the CP electrode. Dramatically enhanced electrocatalytic activity was exemplified at the DC/IL–CTP electrode, as an electrochemical sensor to study the electro oxidation of levodopa (LD) and carbidopa (CD). Based on differential pulse voltammetry (DPV), the oxidation of LD and CD exhibited the dynamic range between 0.10– 900.0 μM and 20.0–900.0 μM respectively, and the detection limit (3σ) for LD and CD were 41 nM and 0.38 μM, respectively. DPV was used for simultaneous determination of LD and CD at the DC/IL–CTP electrode, and quantitation of LD and CD in some real samples (such as tablets of Parkin-C Fort and Madopar

  7. nanoparticles

    Science.gov (United States)

    Andreu-Cabedo, Patricia; Mondragon, Rosa; Hernandez, Leonor; Martinez-Cuenca, Raul; Cabedo, Luis; Julia, J. Enrique

    2014-10-01

    Thermal energy storage (TES) is extremely important in concentrated solar power (CSP) plants since it represents the main difference and advantage of CSP plants with respect to other renewable energy sources such as wind, photovoltaic, etc. CSP represents a low-carbon emission renewable source of energy, and TES allows CSP plants to have energy availability and dispatchability using available industrial technologies. Molten salts are used in CSP plants as a TES material because of their high operational temperature and stability of up to 500°C. Their main drawbacks are their relative poor thermal properties and energy storage density. A simple cost-effective way to improve thermal properties of fluids is to dope them with nanoparticles, thus obtaining the so-called salt-based nanofluids. In this work, solar salt used in CSP plants (60% NaNO3 + 40% KNO3) was doped with silica nanoparticles at different solid mass concentrations (from 0.5% to 2%). Specific heat was measured by means of differential scanning calorimetry (DSC). A maximum increase of 25.03% was found at an optimal concentration of 1 wt.% of nanoparticles. The size distribution of nanoparticle clusters present in the salt at each concentration was evaluated by means of scanning electron microscopy (SEM) and image processing, as well as by means of dynamic light scattering (DLS). The cluster size and the specific surface available depended on the solid content, and a relationship between the specific heat increment and the available particle surface area was obtained. It was proved that the mechanism involved in the specific heat increment is based on a surface phenomenon. Stability of samples was tested for several thermal cycles and thermogravimetric analysis at high temperature was carried out, the samples being stable.

  8. Nanoparticle formulation enhanced protective immunity provoked by PYGPI8p-transamidase related protein (PyTAM) DNA vaccine in Plasmodium yoelii malaria model.

    Science.gov (United States)

    Cherif, Mahamoud Sama; Shuaibu, Mohammed Nasir; Kodama, Yukinobu; Kurosaki, Tomoaki; Helegbe, Gideon Kofi; Kikuchi, Mihoko; Ichinose, Akitoyo; Yanagi, Tetsuo; Sasaki, Hitoshi; Yui, Katsuyuki; Tien, Nguyen Huy; Karbwang, Juntra; Hirayama, Kenji

    2014-04-07

    We have previously reported the new formulation of polyethylimine (PEI) with gamma polyglutamic acid (γ-PGA) nanoparticle (NP) to have provided Plasmodium yoelii merozoite surface protein-1 (PyMSP-1) plasmid DNA vaccine with enhanced protective cellular and humoral immunity in the lethal mouse malaria model. PyGPI8p-transamidase-related protein (PyTAM) was selected as a possible candidate vaccine antigen by using DNA vaccination screening from 29 GPI anchor and signal sequence motif positive genes picked up using web-based bioinformatics tools; though the observed protection was not complete. Here, we observed augmented protective effect of PyTAM DNA vaccine by using PEI and γ-PGA complex as delivery system. NP-coated PyTAM plasmid DNA immunized mice showed a significant survival rate from lethal P. yoelii challenge infection compared with naked PyTAM plasmid or with NP-coated empty plasmid DNA group. Antigen-specific IgG1 and IgG2b subclass antibody levels, proportion of CD4 and CD8T cells producing IFN-γ in the splenocytes and IL-4, IFN-γ, IL-12 and TNF-α levels in the sera and in the supernatants from ex vivo splenocytes culture were all enhanced by the NP-coated PyTAM DNA vaccine. These data indicates that NP augments PyTAM protective immune response, and this enhancement was associated with increased DC activation and concomitant IL-12 production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Albumin-stabilized fluorescent silver nanodots

    Science.gov (United States)

    Sych, Tomash; Polyanichko, Alexander; Kononov, Alexei

    2017-07-01

    Ligand-stabilized Ag nanoclusters (NCs) possess many attractive features including high fluorescence quantum yield, large absorption cross-section, good photostability, large Stokes shift and two-photon absorption cross sections. While plenty of fluorescent clusters have been synthesized on various polymer templates, only a few studies have been reported on the fluorescent Ag clusters on peptides and proteins. We study silver NCs synthesized on different protein matrices, including bovine serum albumin, human serum albumin, egg albumin, equine serum albumin, and lysozyme. Our results show that red-emitting Ag NCs can effectively be stabilized by the disulfide bonds in proteins and that the looser structure of the denatured protein favors formation of the clusters.

  10. Preliminary formulation and characterization of solid lipid nanoparticles containing chloroquine and a P-glycoprotein inhibitor: Influences of lipid-surfactant ratios

    CSIR Research Space (South Africa)

    Nzekwe, IT

    2015-02-01

    Full Text Available with ratio of surfactant to lipid and also total excipients concentration. Drug encapsulation was higher than 50 % in all cases. Equal lipid-surfactant systems achieved higher loading than unequal ratios. The nanoparticle dispersion exhibited biphasic drug...

  11. Preparation of Calcium Phosphate/pDNA Nanoparticles for Exogenous Gene Delivery by Co-Precipitation Method: Optimization of Formulation Variables Using Box-Behnken Design.

    Science.gov (United States)

    Li, Wenpan; Zhang, Xirui; Jing, Shasha; Xin, Xiu; Chen, Kang; Chen, Dawei; Hu, Haiyang

    2017-08-01

    This research focused on optimizing the preparations of pDNA-loaded calcium phosphate (CaP) nanoparticles by employing a 3-factor, 3-level Box-Behnken design. Results indicated that a Ca/P ratio of 189.56, pH of 7.82, and a stirring speed of 528.83 rpm were the optimum conditions for preparation of the nanoparticles. The size of the optimized CaP/pDNA nanoparticles was 61.3 ± 3.64 nm, with a polydispersity index of 0.341 and an encapsulation efficiency of up to 92.11%. The optimized CaP/pDNA nanoparticles had high transfection efficiency and demonstrated good biocompatibility in vitro. Therefore, the Box-Behnken design method was successful in providing desirable CaP nanoparticle pDNA delivery systems by optimizing the experimental factors. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  12. Development and in vivo evaluation of an innovative "Hydrochlorothiazide-in Cyclodextrins-in Solid Lipid Nanoparticles" formulation with sustained release and enhanced oral bioavailability for potential hypertension treatment in pediatrics.

    Science.gov (United States)

    Cirri, Marzia; Mennini, Natascia; Maestrelli, Francesca; Mura, Paola; Ghelardini, Carla; Di Cesare Mannelli, Lorenzo

    2017-04-15

    An innovative pediatric oral formulation of hydrochlorothiazide (HCT) (2mg/mL), endowed with improved bioavailability and sustained release properties and suitable for the hypertension treatment in pediatric patients, was developed by combining the drug-cyclodextrin complexation and the incorporation of the complex into Solid Lipid Nanoparticles (SLN). Precirol ® ATO5-based SLN, with two different surfactants (Pluronic ® F68 and Tween ® 80) loaded with the drug as such or as binary system with hydroxypropyl-beta-cyclodextrin (HPβCd) and sulfobutyl-ether-beta-cyclodextrin (SBEβCd) both as physical mixture (P.M.) or coground product (GR), were prepared using the hot high-shear homogenization followed by ultrasonication method. Loading of the drug:HPβCd both as P.M. and GR gave rise to nanoparticle formation, differently from the HCT:SBEβCd ones, with an entrapment efficiency of about 65%. Such SLN formulations showed an improvement of the drug release rate compared both to the drug suspension and to the free drug-loaded SLN. In all cases the SLN containing the GR systems exhibited better performances than the corresponding with P.M. However, the presence of Tween ® 80 gave rise to the complete drug release after only 150min, without providing a sustained release, whereas Pluronic ® F68-based SLN containing GR were able to assure a sustained release over the time achieving more than 75% drug released at the end of the test, maintaining a constant 1.8-fold increase respect to simple drug suspension. Pluronic ® F68-based SLN showed a pharmaceutically acceptable stability up to three months. In vivo studies highlighted the effectiveness of such formulations, enabling a concomitant increased diuretic effect and a sustained drug release and, consequently, enhanced HCT oral bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. In vivo evaluation of a conjugated poly(lactide-ethylene glycol nanoparticle depot formulation for prolonged insulin delivery in the diabetic rabbit model

    Directory of Open Access Journals (Sweden)

    Tomar L

    2013-02-01

    Full Text Available Lomas Tomar,1,2 Charu Tyagi,1,3 Manoj Kumar,2 Pradeep Kumar,1 Harpal Singh,2 Yahya E Choonara,1 Viness Pillay11University of the Witwatersrand, Faculty of Health Sciences, Department of Pharmacy and Pharmacology, Johannesburg, Gauteng, South Africa; 2Centre for Biomedical Engineering, Indian Institute of Technology, Delhi, India; 3VSPG College, Chaudhary Charan Singh University, Meerut, IndiaAbstract: Poly(ethylene glycol (PEG and polylactic acid (PLA-based copolymeric nanoparticles were synthesized and investigated as a carrier for prolonged delivery of insulin via the parenteral route. Insulin loading was simultaneously achieved with particle synthesis using a double emulsion solvent evaporation technique, and the effect of varied PEG chain lengths on particle size and insulin loading efficiency was determined. The synthesized copolymer and nanoparticles were analyzed by standard polymer characterization techniques of gel permeation chromatography, dynamic light scattering, nuclear magnetic resonance, and transmission electron microscopy. In vitro insulin release studies performed under simulated conditions provided a near zero-order release pattern up to 10 days. In vivo animal studies were undertaken with varied insulin loads of nanoparticles administered subcutaneously to fed diabetic rabbits and, of all doses administered, nanoparticles containing 50 IU of insulin load per kg body weight controlled the blood glucose level within the physiologically normal range of 90–140 mg/dL, and had a prolonged effect for more than 7 days. Histopathological evaluation of tissue samples from the site of injection showed no signs of inflammation or aggregation, and established the nontoxic nature of the prepared copolymeric nanoparticles. Further, the reaction profiles for PLA-COOH and NH2-PEGDA-NH2 were elucidated using molecular mechanics energy relationships in vacuum and in a solvated system by exploring the spatial disposition of various

  14. Novel Formulations for Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ana Maria Carmona-Ribeiro

    2014-10-01

    Full Text Available Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

  15. Effect of chain length and electrical charge on properties of ammonium-bearing bisphosphonate-coated superparamagnetic iron oxide nanoparticles: formulation and physicochemical studies

    Energy Technology Data Exchange (ETDEWEB)

    Karimi, Ali [Inserm U646, Universite d' Angers (France); Denizot, Benoit, E-mail: BDenizot@chi-annemasse-bonneville.f [Centre Hospitalier Annemasse-Bonneville (France); Hindre, Francois [Inserm U646, Universite d' Angers (France); Filmon, Robert [Universite d' Angers, Service Commun d' Imagerie et d' Analyses Microscopiques (France); Greneche, Jean-Marc [Universite du Mans, Laboratoire de Physique de I' Etat Condense UMR 6087 (France); Laurent, Sophie [NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, Department of General, Organic and Biochemical Chemistry (Belgium); Daou, T. Jean [UMR CNRS-ULP 7504, Institut de Physique et Chimie des Materiaux de Strasbourg (France); Begin-Colin, Sylvie [Universite de Haute Alsace, Laboratoire de Materiaux a Porosite Controlee, UMR CNRS 7016 (France); Jeune, Jean-Jacques Le [Inserm U646, Universite d' Angers (France)

    2010-05-15

    Bisphosphonates BP molecules have shown to be efficient for coating superparamagnetic iron oxide particles. In order to clarify the respective roles of electrical charge and the length of the molecules, bisphosphonates with one or two ammonium moieties with an intermediate aliphatic group of 3, 5 or 7 carbons were synthesized and iron oxide nanoparticles coated. The evaluation on their iron core properties was made by transmission electron microscopy (TEM), nuclear magnetic relaxation dispersion (NMRD) profiles and Moessbauer spectra. The core size is close to 5 nm, with a global superparamagnetic behaviour modified by a paramagnetic Fe-based layer, probably due to surface crystal alteration. The hydrodynamic sizes increase slightly with aliphatic chain length (from 9.8 to 18.6 nm). The presence of one or two ammonium group(s) lowers the negative electrophoretic mobility up to bear zero values but reduces their colloidal stability. These BP-coated iron oxide nanoparticles are promising Magnetic Resonance Imaging (MRI) contrast agents.

  16. Nanoparticle-Mediated p53 Gene Therapy for Breast Cancer

    National Research Council Canada - National Science Library

    Prabha, Swayam

    2003-01-01

    The effect of different formulation parameters on nanoparticle-mediated gene transfection in vitro was studied Nanoparticles encapsulating plasmid DNA encoding fire fly luciferase were formulated using poly lactide (PLA...

  17. A new optimized formulation of cationic solid lipid nanoparticles intended for gene delivery: development, characterization and DNA binding efficiency of TCERG1 expression plasmid.

    Science.gov (United States)

    Fàbregas, Anna; Sánchez-Hernández, Noemí; Ticó, Josep Ramon; García-Montoya, Encarna; Pérez-Lozano, Pilar; Suñé-Negre, Josep M; Hernández-Munain, Cristina; Suñé, Carlos; Miñarro, Montserrat

    2014-10-01

    Solid lipid nanoparticles (SLNs) are being considered as a new approach for therapeutics for many known diseases. In addition to drug delivery, their use as non-viral vectors for gene delivery can be achieved by the inclusion of cationic lipids, which provide a positive surface potential that favours binding to the DNA backbone. This work is based on the idea that the optimization of the components is required as the first step in simplifying the qualitative and quantitative composition of SLNs as much as possible without affecting the essential properties that define SLNs as optimal non-viral vectors for gene delivery. We selected the best lipids and surfactants in terms of particle size and zeta potential and characterized the properties of the resulting nanoparticles using X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The SLNs had a particle size of approximately 120 nm and a positive surface charge of 42 mV. In addition, we analysed the main physicochemical characteristics of the bulk components of the nanoparticles using X-ray diffraction (XRD), differential scanning calorimetry (DSC) and mass spectrometry (MS). The suitability of the optimized SLNs for DNA binding was evaluated after the lyophilisation process using a carboxyl-terminal region of the TCERG1 gene, a human factor that has been implicated in several diseases. We show that the SLNs presented high efficiency in the binding of DNA, and importantly, they presented no toxicity when assayed in an in vivo system. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Design and formulation of nano-sized spray dried efavirenz. Part I: Influence of formulation parameters

    CSIR Research Space (South Africa)

    Katata, L

    2012-10-01

    Full Text Available statistical design with an L8 orthogonal array, was implemented to optimise the formulation parameters of PCL-EFV nanoparticles. The types of sugar (lactose or trehalose), surfactant concentration and solvent (dichloromethane and ethyl acetate) were chosen...

  19. Diagnostic formulation

    OpenAIRE

    Kuruvilla, K.; Kuruvilla, Anju

    2010-01-01

    Writing a ?Diagnostic Formulation? is a skill expected of candidates in the post-graduate examinations in psychiatry in most universities in India. However there is ambiguity regarding what the term means and how it should be written. This article is an attempt to provide some guidelines on this topic.

  20. Mucus and Cell-Penetrating Nanoparticles Embedded in Nano-into-Micro Formulations for Pulmonary Delivery of Ivacaftor in Patients with Cystic Fibrosis.

    Science.gov (United States)

    Porsio, Barbara; Craparo, Emanuela Fabiola; Mauro, Nicolò; Giammona, Gaetano; Cavallaro, Gennara

    2018-01-10

    Here, mucus-penetrating nanoparticles (NPs) for pulmonary administration of ivacaftor in patients with cystic fibrosis (CF) were produced with the dual aim of enhancing ivacaftor delivery to the airway epithelial cells, by rapid diffusion through the mucus barrier, and at the same time, promoting ivacaftor lung cellular uptake. Pegylated and Tat-decorated fluorescent nanoparticles (FNPs) were produced by nanoprecipitation, starting from two synthetic copolymers, and showed nanometric sizes (∼70 nm), a slightly negative ζ potential, and high cytocompatibility toward human bronchial epithelium cells. After having showed the significant presence of poly(ethylene glycol) chains and Tat protein onto the FNP surface, the FNP mucus-penetrating ability, ivacaftor release profile, and lung cellular uptake were studied in the presence of CF-artificial mucus as a function of the FNP surface chemical composition. Moreover, microparticle-based pulmonary drug-delivery systems composed of mucus-penetrating FNPs loaded with ivacaftor and mannitol were prepared by using the nano-into-micro strategy and realized by spray-drying, thereby providing optimal preservation and stabilization of FNP technological and fluorescence properties.

  1. Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone and poly(lactide-co-glycolide-co-caprolactone for prostate cancer treatment: formulation, characterization, and cytotoxicity studies

    Directory of Open Access Journals (Sweden)

    Sechi Mario

    2011-01-01

    Full Text Available Abstract Docetaxel (Dtx chemotherapy is the optional treatment in patients with hormone-refractory metastatic prostate cancer, and Dtx-loaded polymeric nanoparticles (NPs have the potential to induce durable clinical responses. However, alternative formulations are needed to overcome the serious side effects, also due to the adjuvant used, and to improve the clinical efficacy of the drug. In the present study, two novel biodegradable block-copolymers, poly(lactide-co-caprolactone (PLA-PCL and poly(lactide-co-caprolactone-co-glycolide (PLGA-PCL, were explored for the formulation of Dtx-loaded NPs and compared with PLA- and PLGA-NPs. The nanosystems were prepared by an original nanoprecipitation method, using Pluronic F-127 as surfactant agent, and were characterized in terms of morphology, size distribution, encapsulation efficiency, crystalline structure, and in vitro release. To evaluate the potential anticancer efficacy of a nanoparticulate system, in vitro cytotoxicity studies on human prostate cancer cell line (PC3 were carried out. NPs were found to be of spherical shape with an average diameter in the range of 100 to 200 nm and a unimodal particle size distribution. Dtx was incorporated into the PLGA-PCL NPs with higher (p < 0.05 encapsulation efficiency than that of other polymers. Differential scanning calorimetry suggested that Dtx was molecularly dispersed in the polymeric matrices. In vitro drug release study showed that release profiles of Dtx varied on the bases of characteristics of polymers used for formulation. PLA-PCL and PLGA-PCL drug loaded NPs shared an overlapping release profiles, and are able to release about 90% of drug within 6 h, when compared with PLA- and PLGA-NPs. Moreover, cytotoxicity studies demonstrated advantages of the Dtx-loaded PLGA-PCL NPs over pure Dtx in both time- and concentration-dependent manner. In particular, an increase of 20% of PC3 growth inhibition was determined by PLGA-PCL NPs with respect to

  2. Neuroprotective and Neurorescue Effects of a Novel Polymeric Nanoparticle Formulation of Curcumin (NanoCurc™) in the Neuronal Cell Culture and Animal Model: Implications for Alzheimer’s Disease

    Science.gov (United States)

    Ray, Balmiki; Bisht, Savita; Maitra, Amarnath; Maitra, Anirban; Lahiri, Debomoy K.

    2012-01-01

    Alzheimer’s disease (AD) is characterized by deposition of amyloid-β (Aβ) plaques within the brain parenchyma followed by synaptic loss and neuronal death. Deposited Aβ reacts with activated microglia to produce reactive oxygen species (ROS) and cytochemokines, which lead to severe neuroinflammation. Curcumin is a yellow polyphenol compound found in turmeric, a widely used culinary ingredient that possesses anti-inflammatory and anti-cancer properties and may show efficacy as a potential therapeutic agent in several neuro-inflammatory diseases including AD. However, poor aqueous solubility and sub-optimal systemic absorption from the gastrointestinal tract may represent factors contributing to its failure in clinical trials. To increase curcumin’s bioavailability, a polymeric nanoparticle encapsulated curcumin (NanoCurc™) was formulated which is completely water soluble. NanoCurc™ treatment protects neuronally differentiated human SK-N-SH cells from ROS (H2O2) mediated insults. NanoCurc™ also rescues differentiated human SK-N-SH cells, which were previously insulted with H2O2. In vivo, intraperitoneal (IP) NanoCurc™ injection at a dose of 25 mg/kg twice daily in athymic mice resulted in significant curcumin levels in the brain (0.32 μg/g). Biochemical study of NanoCurc™-treated athymic mice revealed decreased levels of H2O2 as well as caspase 3 and caspase 7 activities in the brain, accompanied by increased glutathione (GSH) concentrations. Increased free to oxidized glutathione (GSH : GSSH) ratio in athymic mice brain versus controls also indicated a favorable redox intracellular environment. Taken together, these results suggest that NanoCurc™ represents an optimized formulation worthy of assessing the therapeutic value of curcumin in AD. PMID:20930270

  3. Eco-Friendly Formulated Zinc Oxide Nanoparticles: Induction of Cell Cycle Arrest and Apoptosis in the MCF-7 Cancer Cell Line

    Science.gov (United States)

    Boroumand Moghaddam, Amin; Moniri, Mona; Abdul Rahim, Raha; Bin Ariff, Arbakariya; Navaderi, Mohammad

    2017-01-01

    Green products have strong potential in the discovery and development of unique drugs. Zinc oxide nanoparticles (ZnO NPs) have been observed to have powerful cytotoxicity against cells that cause breast cancer. The present study aims to examine the cell cycle profile, status of cell death, and pathways of apoptosis in breast cancer cells (MCF-7) treated with biosynthesized ZnO NPs. The anti-proliferative activity of ZnO NPs was determined using MTT assay. Cell cycle analysis and the mode of cell death were evaluated using a flow cytometry instrument. Quantitative real-time-PCR (qRT-PCR) was employed to investigate the expression of apoptosis in MCF-7 cells. ZnO NPs were cytotoxic to the MCF-7 cells in a dose-dependent manner. The 50% growth inhibition concentration (IC50) of ZnO NPs at 24 h was 121 µg/mL. Cell cycle analysis revealed that ZnO NPs induced sub-G1 phase (apoptosis), with values of 1.87% at 0 μg/mL (control), 71.49% at IC25, 98.91% at IC50, and 99.44% at IC75. Annexin V/propidium iodide (PI) flow cytometry analysis confirmed that ZnO NPs induce apoptosis in MCF-7 cells. The pro-apoptotic genes p53, p21, Bax, and JNK were upregulated, whereas anti-apoptotic genes Bcl-2, AKT1, and ERK1/2 were downregulated in a dose-dependent manner. The arrest and apoptosis of MCF-7 cells were induced by ZnO NPs through several signalling pathways. PMID:29053567

  4. In Vitro Efficacy of Free and Nanoparticle Formulations of Gallium(III) meso-Tetraphenylporphyrine against Mycobacterium avium and Mycobacterium abscessus and Gallium Biodistribution in Mice.

    Science.gov (United States)

    Choi, Seoung-Ryoung; Britigan, Bradley E; Switzer, Barbara; Hoke, Traci; Moran, David; Narayanasamy, Prabagaran

    2018-03-05

    The nontuberculous mycobacterial (NTM) pathogens, M. avium complex (MAC) and M. abscessus, can result in severe pulmonary infections. Current antibiotics confront significant challenges for treatment of these NTM infections due to emerging multidrug-resistance. Thus, development of new antibiotics targeted against these agents is needed. We examined the inhibitory activities of Ga(NO 3 ) 3 , GaCl 3 , gallium meso-tetraphenylporphyrine (GaTP), and gallium nanoparticles (GaNP) against intra- and extracellular M. avium and M. abscessus. GaTP, an analogue of natural heme, inhibited growth of both M. avium and M. abscessus with MICs in Fe-free 7H9 media of 0.5 and 2 μg/mL, respectively. GaTP was more active than Ga(NO 3 ) 3 and GaCl 3 . Ga(NO 3 ) 3 and GaCl 3 were not as active in Fe-rich media compared to Fe-free media. However, GaTP was much less impacted by exogenous Fe, with MICs against M. avium and M. abscessus of 2 and 4 μg/mL, respectively, in 7H9 OADC media (Fe rich). Confocal microscopy showed that GaNP penetrates the M. avium cell wall. As assessed by determining colony forming units, GaNP inhibited the growth of NTM growing in THP-1 macrophages up to 15 days after drug-loading of the cells, confirming a prolonged growth inhibitory activity of the GaNP. Biodistribution studies of GaNP conducted in mice showed that intraperitoneal injection is more effective than intramuscular injection in delivering Ga(III) into lung tissue. GaTP exhibits potential as a lead compound for development of anti-NTM agents that target heme-bound iron uptake mechanisms by mycobacteria and inhibit growth by disrupting mycobacterial iron acquisition/utilization.

  5. Formulation and Optimization of Polymeric Nanoparticles for Intranasal Delivery of Lorazepam Using Box-Behnken Design: In Vitro and In Vivo Evaluation

    Science.gov (United States)

    Sharma, Deepak; Maheshwari, Dipika; Rana, Ravish; Bhatia, Shanu; Singh, Manisha; Gabrani, Reema; Sharma, Sanjeev K.; Ali, Javed; Sharma, Rakesh Kumar; Dang, Shweta

    2014-01-01

    The aim of the present study was to optimize lorazepam loaded PLGA nanoparticles (Lzp-PLGA-NPs) by investigating the effect of process variables on the response using Box-Behnken design. Effect of four independent factors, that is, polymer, surfactant, drug, and aqueous/organic ratio, was studied on two dependent responses, that is, z-average and % drug entrapment. Lzp-PLGA-NPs were successfully developed by nanoprecipitation method using PLGA as polymer, poloxamer as surfactant and acetone as organic phase. NPs were characterized for particle size, zeta potential, % drug entrapment, drug release behavior, TEM, and cell viability. Lzp-PLGA-NPs were characterized for drug polymer interaction using FTIR. The developed NPs showed nearly spherical shape with z-average 167–318 d·nm, PDI below 0.441, and −18.4 mV zeta potential with maximum % drug entrapment of 90.1%. In vitro drug release behavior followed Korsmeyer-Peppas model and showed initial burst release of 21.7 ± 1.3% with prolonged drug release of 69.5 ± 0.8% from optimized NPs up to 24 h. In vitro drug release data was found in agreement with ex vivo permeation data through sheep nasal mucosa. In vitro cell viability study on Vero cell line confirmed the safety of optimized NPs. Optimized Lzp-PLGA-NPs were radiolabelled with Technitium-99m for scintigraphy imaging and biodistribution studies in Sprague-Dawley rats to establish nose-to-brain pathway. PMID:25126544

  6. Formulation and Optimization of Polymeric Nanoparticles for Intranasal Delivery of Lorazepam Using Box-Behnken Design: In Vitro and In Vivo Evaluation

    Directory of Open Access Journals (Sweden)

    Deepak Sharma

    2014-01-01

    Full Text Available The aim of the present study was to optimize lorazepam loaded PLGA nanoparticles (Lzp-PLGA-NPs by investigating the effect of process variables on the response using Box-Behnken design. Effect of four independent factors, that is, polymer, surfactant, drug, and aqueous/organic ratio, was studied on two dependent responses, that is, z-average and % drug entrapment. Lzp-PLGA-NPs were successfully developed by nanoprecipitation method using PLGA as polymer, poloxamer as surfactant and acetone as organic phase. NPs were characterized for particle size, zeta potential, % drug entrapment, drug release behavior, TEM, and cell viability. Lzp-PLGA-NPs were characterized for drug polymer interaction using FTIR. The developed NPs showed nearly spherical shape with z-average 167–318 d·nm, PDI below 0.441, and −18.4 mV zeta potential with maximum % drug entrapment of 90.1%. In vitro drug release behavior followed Korsmeyer-Peppas model and showed initial burst release of 21.7±1.3% with prolonged drug release of 69.5±0.8% from optimized NPs up to 24 h. In vitro drug release data was found in agreement with ex vivo permeation data through sheep nasal mucosa. In vitro cell viability study on Vero cell line confirmed the safety of optimized NPs. Optimized Lzp-PLGA-NPs were radiolabelled with Technitium-99m for scintigraphy imaging and biodistribution studies in Sprague-Dawley rats to establish nose-to-brain pathway.

  7. Eco-Friendly Formulated Zinc Oxide Nanoparticles: Induction of Cell Cycle Arrest and Apoptosis in the MCF-7 Cancer Cell Line.

    Science.gov (United States)

    Boroumand Moghaddam, Amin; Moniri, Mona; Azizi, Susan; Abdul Rahim, Raha; Bin Ariff, Arbakariya; Navaderi, Mohammad; Mohamad, Rosfarizan

    2017-10-20

    Green products have strong potential in the discovery and development of unique drugs. Zinc oxide nanoparticles (ZnO NPs) have been observed to have powerful cytotoxicity against cells that cause breast cancer. The present study aims to examine the cell cycle profile, status of cell death, and pathways of apoptosis in breast cancer cells (MCF-7) treated with biosynthesized ZnO NPs. The anti-proliferative activity of ZnO NPs was determined using MTT assay. Cell cycle analysis and the mode of cell death were evaluated using a flow cytometry instrument. Quantitative real-time-PCR (qRT-PCR) was employed to investigate the expression of apoptosis in MCF-7 cells. ZnO NPs were cytotoxic to the MCF-7 cells in a dose-dependent manner. The 50% growth inhibition concentration (IC 50 ) of ZnO NPs at 24 h was 121 µg/mL. Cell cycle analysis revealed that ZnO NPs induced sub-G₁ phase (apoptosis), with values of 1.87% at 0 μg/mL (control), 71.49% at IC 25 , 98.91% at IC 50 , and 99.44% at IC 75 . Annexin V/propidium iodide (PI) flow cytometry analysis confirmed that ZnO NPs induce apoptosis in MCF-7 cells. The pro-apoptotic genes p53 , p21 , Bax , and JNK were upregulated, whereas anti-apoptotic genes Bcl-2 , AKT1 , and ERK1/2 were downregulated in a dose-dependent manner. The arrest and apoptosis of MCF-7 cells were induced by ZnO NPs through several signalling pathways.

  8. Preparation of nanoscale pulmonary drug delivery formulations by spray drying

    DEFF Research Database (Denmark)

    Bohr, Adam; Ruge, Christian A; Beck-Broichsitter, Moritz

    2014-01-01

    Advances in preparation technologies for nanomedicines have provided novel formulations for pulmonary drug delivery. Application of drugs via the lungs can be considered as one of the most attractive implementations of nanoparticles for therapeutic use due to the unique anatomy and physiology...... of the lungs. The colloidal nature of nanoparticles provides important advantages to the formulation of drugs, which are normally difficult to administer due to poor stability or uptake, partly because nanoparticles protect the drug from the physiological milieu, facilitate transport across biological barriers...... and can offer controlled drug release. There are numerous methods for producing therapeutic nanoparticles, each with their own advantages and suitable application. Liquid atomization techniques such as spray drying can produce nanoparticle formulations in a dry powder form suitable for pulmonary...

  9. Formulation and development of colon-targeted mucopenetrating ...

    African Journals Online (AJOL)

    Purpose: To formulation and develop colon-targeted mucopenetrating metronidazole nanoparticles. Methods: Metronidazole-loaded chitosan nanoparticles with a pH-sensitive polymer, hydroxyl propyl methyl cellulose phthalate (HPMCP), were prepared by ionic gelation technique and then coated with Eudragit S100 by ...

  10. Crystallization Formulation Lab

    Data.gov (United States)

    Federal Laboratory Consortium — The Crystallization Formulation Lab fills a critical need in the process development and optimization of current and new explosives and energetic formulations. The...

  11. IT Supporting Strategy Formulation

    NARCIS (Netherlands)

    Achterbergh, J.M.I.M.; Khosrow-Pour, M.

    2005-01-01

    This overview approaches information and communication technology (ICT) for competitive intelligence from the perspective of strategy formulation. It provides an ICT architecture for supporting the knowledge processes producing relevant knowledge for strategy formulation. To determine what this

  12. Functionalization of biosynthesized gold nanoparticle from aqueous ...

    African Journals Online (AJOL)

    The biosynthesized nanoparticles and formulated nanodrug were characterized using UV-Vis spectrophotometry, Zetasizer, Scanning and transmission Electron Microscopy (SEM; TEM), Energy Dispersive spectrophotometry (EDAX) and Fourier Transform Infra-red Spectroscopy. Polyethylene glycol and Lincomycin were ...

  13. Aquaculture project formulation

    National Research Council Canada - National Science Library

    Insull, David; Nash, Colin E

    1990-01-01

    .... The first part of the document contains a broad introduction to project formulation, describing the integration of aquaculture projects within development plans, the organization and management...

  14. Explosive Formulation Pilot Plant

    Data.gov (United States)

    Federal Laboratory Consortium — The Pilot Plant for Explosive Formulation supports the development of new explosives that are comprised of several components. This system is particularly beneficial...

  15. Formulation and optimization of oxaliplatin immuno-nanoparticles using Box-Behnken design and cytotoxicity assessment for synergistic and receptor-mediated targeting in the treatment of colorectal cancer.

    Science.gov (United States)

    Tummala, Shashank; Gowthamarajan, K; Satish Kumar, M N; Praveen, T K; Yamjala, Karthik; Tripuraneni, Naga Srinivas; Prakash, Ashwati

    2016-12-01

    Conventional chemotherapy majorly lacks clinical application attributed to its inspecificity, adverse effects and inability to penetrate into tumor cells. Hence, the aim of the study was to prepare oxaliplatin solid lipid nanoparticles (OP-SLN) by microemulsion method optimizing it by Box-Behnken design and then covalently conjugated to TRAIL (CD-253) monoclonal antibody (TR-OP-SLN) for targeting colorectal cancer cells. The optimized OP-SLN3 has shown an appreciable particle size (121 ± 1.22 nm), entrapment efficiency (78 ± 0.09%) and drug loading (32 ± 1.01%). Fluorescence study and the Bradford assay further confirmed the binding of the protein. A 1.5-fold increase in cytotoxicity of immuno-nanoparticles (4.9 μM) was observed.

  16. Functionalization of Biosynthesized Gold Nanoparticle from ...

    African Journals Online (AJOL)

    Dr Olaleye

    nanoparticles and formulated nanodrug were characterized using UV-Vis spectrophotometry, Zetasizer, Scanning and transmission Electron Microscopy .... UV–Vis Spectrophotometer (UV-1800 Shimadzu) was used to measure the wavelength .... plasma resonance at 545.5nm for biosynthesized gold nanoparticle using ...

  17. Audits of radiopharmaceutical formulations

    International Nuclear Information System (INIS)

    Castronovo, F.P. Jr.

    1992-01-01

    A procedure for auditing radiopharmaceutical formulations is described. To meet FDA guidelines regarding the quality of radiopharmaceuticals, institutional radioactive drug research committees perform audits when such drugs are formulated away from an institutional pharmacy. All principal investigators who formulate drugs outside institutional pharmacies must pass these audits before they can obtain a radiopharmaceutical investigation permit. The audit team meets with the individual who performs the formulation at the site of drug preparation to verify that drug formulations meet identity, strength, quality, and purity standards; are uniform and reproducible; and are sterile and pyrogen free. This team must contain an expert knowledgeable in the preparation of radioactive drugs; a radiopharmacist is the most qualified person for this role. Problems that have been identified by audits include lack of sterility and apyrogenicity testing, formulations that are open to the laboratory environment, failure to use pharmaceutical-grade chemicals, inadequate quality control methods or records, inadequate training of the person preparing the drug, and improper unit dose preparation. Investigational radiopharmaceutical formulations, including nonradiolabeled drugs, must be audited before they are administered to humans. A properly trained pharmacist should be a member of the audit team

  18. DNA/RNA-based formulations for treatment of breast cancer

    DEFF Research Database (Denmark)

    Xie, Zhaolu; Zeng, Xianghui

    2017-01-01

    utilized targets are not effective enough as monotherapy for breast cancer. Secondly, the requirements for co-delivery system make the preparation of formulation more complicated. Thirdly, nanoparticles with the modification of tumor-targeting ligands could be more unstable in circulation and normal...

  19. Formulation of a New Generation of Liposomes from Bacterial and ...

    African Journals Online (AJOL)

    http://dx.doi.org/10.4314/tjpr.v15i2.1. Original Research Article. Formulation of a New Generation of Liposomes from ... extracted from Escherichia coli (E. coli) cultures, and archaeosomes made with lipids derived from .... Krishnamachari Y, Geary SM, Lemke CD, Salem AK. Nanoparticle delivery systems in cancer vaccines.

  20. Evaluation of nanoparticle immunotoxicity

    Science.gov (United States)

    Dobrovolskaia, Marina A.; Germolec, Dori R.; Weaver, James L.

    2009-07-01

    The pharmaceutical industry is developing increasing numbers of drugs and diagnostics based on nanoparticles, and evaluating the immune response to these diverse formulations has become a challenge for scientists and regulatory agencies alike. An international panel of scientists and representatives from various agencies and companies reviewed the imitations of current tests at a workshop held at the National Cancer Institute in Frederick, Maryland. This article outlines practical strategies for identifying and controlling interferences in common evaluation methods and the implications for regulation.

  1. Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: challenges, considerations and strategy

    OpenAIRE

    Dobrovolskaia, Marina A.

    2015-01-01

    Assorted challenges in physicochemical characterization, sterilization, depyrogenation, and in the assessment of pharmacology, safety, and efficacy profiles accompany preclinical development of nanotechnology-formulated drugs. Some of these challenges are not unique to nanotechnology and are common in the development of other pharmaceutical products. However, nanoparticle-formulated drugs are biochemically sophisticated, which causes their translation into the clinic to be particularly comple...

  2. Cytotoxicity and ion release of alloy nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, Anne [Laser Zentrum Hannover e.V (Germany); Fuhlrott, Jutta; Loos, Anneke [Hannover Medical School, Biovertraeglichkeitslabor BioMedimplant (Germany); Barcikowski, Stephan, E-mail: stephan.barcikowski@uni-due.de [Laser Zentrum Hannover e.V (Germany)

    2012-01-15

    It is well-known that nanoparticles could cause toxic effects in cells. Alloy nanoparticles with yet unknown health risk may be released from cardiovascular implants made of Nickel-Titanium or Cobalt-Chromium due to abrasion or production failure. We show the bio-response of human primary endothelial and smooth muscle cells exposed to different concentrations of metal and alloy nanoparticles. Nanoparticles having primary particle sizes in the range of 5-250 nm were generated using laser ablation in three different solutions avoiding artificial chemical additives, and giving access to formulations containing nanoparticles only stabilized by biological ligands. Endothelial cells are found to be more sensitive to nanoparticle exposure than smooth muscle cells. Cobalt and Nickel nanoparticles caused the highest cytotoxicity. In contrast, Titanium, Nickel-Iron, and Nickel-Titanium nanoparticles had almost no influence on cells below a nanoparticle concentration of 10 {mu}M. Nanoparticles in cysteine dissolved almost completely, whereas less ions are released when nanoparticles were stabilized in water or citrate solution. Nanoparticles stabilized by cysteine caused less inhibitory effects on cells suggesting cysteine to form metal complexes with bioactive ions in media.

  3. Assessment of strategy formulation

    DEFF Research Database (Denmark)

    Acur, Nuran; Englyst, Linda

    2006-01-01

    approaches to strategy assessment, namely the goal-centred, comparative and improvement approaches, as found in the literature. Furthermore, it encompasses three phases of strategy formulation processes: strategic thinking, strategic planning and embedding of strategy. The tool reflects that the different......, but cases and managerial perceptions indicate that the need for accurate and detailed plans might be overrated in the literature, as implementation relies heavily on continuous improvement and empowerment. Concerning embedding, key aspects relate both to the goal-centred and improvement approaches, while...... for strategy formulation processes that ensures high quality in process and outcome. Design/methodology/approach – A literature review was conducted to identify success criteria for strategy formulation processes. Then, a simple questionnaire and assessment tool was developed and used to test the validity...

  4. Lubrication in tablet formulations.

    Science.gov (United States)

    Wang, Jennifer; Wen, Hong; Desai, Divyakant

    2010-05-01

    Theoretical aspects and practical considerations of lubrication in tablet compression are reviewed in this paper. Properties of the materials that are often used as lubricants, such as magnesium stearate, in tablet dosage form are summarized. The manufacturing process factors that may affect tablet lubrication are discussed. As important as the lubricants in tablet formulations are, their presence can cause some changes to the tablet physical and chemical properties. Furthermore, a detailed review is provided on the methodologies used to characterize lubrication process during tablet compression with relevant process analytical technologies. Finally, the Quality-by-Design considerations for tablet formulation and process development in terms of lubrication are discussed.

  5. Nano-formulations of drugs: Recent developments, impact and challenges.

    Science.gov (United States)

    Jeevanandam, Jaison; Chan, Yen San; Danquah, Michael K

    2016-01-01

    Nano-formulations of medicinal drugs have attracted the interest of many researchers for drug delivery applications. These nano-formulations enhance the properties of conventional drugs and are specific to the targeted delivery site. Dendrimers, polymeric nanoparticles, liposomes, nano-emulsions and micelles are some of the nano-formulations that are gaining prominence in pharmaceutical industry for enhanced drug formulation. Wide varieties of synthesis methods are available for the preparation of nano-formulations to deliver drugs in biological system. The choice of synthesis methods depend on the size and shape of particulate formulation, biochemical properties of drug, and the targeted site. This article discusses recent developments in nano-formulation and the progressive impact on pharmaceutical research and industries. Additionally, process challenges relating to consistent generation of nano-formulations for drug delivery are discussed. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  6. BSA Nanoparticles for siRNA Delivery: Coating Effects on Nanoparticle Properties, Plasma Protein Adsorption, and In Vitro siRNA Delivery

    Directory of Open Access Journals (Sweden)

    Haran Yogasundaram

    2012-01-01

    Full Text Available Developing vehicles for the delivery of therapeutic molecules, like siRNA, is an area of active research. Nanoparticles composed of bovine serum albumin, stabilized via the adsorption of poly-L-lysine (PLL, have been shown to be potentially inert drug-delivery vehicles. With the primary goal of reducing nonspecific protein adsorption, the effect of using comb-type structures of poly(ethylene glycol (1 kDa, PEG units conjugated to PLL (4.2 and 24 kDa on BSA-NP properties, apparent siRNA release rate, cell viability, and cell uptake were evaluated. PEGylated PLL coatings resulted in NPs with ζ-potentials close to neutral. Incubation with platelet-poor plasma showed the composition of the adsorbed proteome was similar for all systems. siRNA was effectively encapsulated and released in a sustained manner from all NPs. With 4.2 kDa PLL, cellular uptake was not affected by the presence of PEG, but PEG coating inhibited uptake with 24 kDa PLL NPs. Moreover, 24 kDa PLL systems were cytotoxic and this cytotoxicity was diminished upon PEG incorporation. The overall results identified a BSA-NP coating structure that provided effective siRNA encapsulation while reducing ζ-potential, protein adsorption, and cytotoxicity, necessary attributes for in vivo application of drug-delivery vehicles.

  7. Inhaled dry powder formulations for treating tuberculosis.

    Science.gov (United States)

    Das, Shyamal; Tucker, Ian; Stewart, Peter

    2015-01-01

    Tuberculosis is the second leading cause of death from infectious diseases. Although antitubercular drugs have been traditionally administered orally, there is a growing interest in delivering drugs via the pulmonary route using nebulisers or dry powder inhalers. Drugs in dry powder inhalers (DPI) are stable and DPI are user-friendly compared to nebulisation which is time consuming, inconvenient and inefficient and requires special equipment. For tuberculosis treatment, drugs should target alveolar macrophages that harbour microorganisms and/or maintain high drug concentration at the infection site in the lung. Drug particles include micro-particles or nanoparticles. Powders can be engineered by micronisation, crystallisation, spray drying, freeze drying and particle coating approaches. The formulation may contain single or combination drugs. This paper will provide an update on current status of TB, its pathogenesis, current treatment strategies, shortcomings of current oral or parenteral delivery strategies, pulmonary delivery devices, advantages of pulmonary delivery of powder formulations, formulation approaches and pharmacokinetic studies of pulmonary delivery of powders for inhalation.

  8. Supercooled smectic nanoparticles

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Koch, Michel H J; Fahr, Alfred

    2009-01-01

    Cholesteryl nonanoate (CN), myristate (CM), palmitate (CP) and oleate (CO) alone or in combination were evaluated as matrix lipids for the preparation of supercooled smectic nanoparticles with a high stability against recrystallization during storage. The phase behavior of the cholesterol esters...... in the bulk was studied by polarizing light microscopy, differential scanning calorimetry (DSC) and small angle X-ray scattering (SAXS). Colloidal dispersions with pure and mixed cholesterol ester matrices were prepared by high-pressure melt homogenization and characterized by photon correlation spectroscopy......, laser diffraction combined with polarizing intensity differential scattering, DSC and SAXS. The morphology of selected formulations was studied by freeze-fracture electron microscopy. All smectic nanoparticles with a mixed cholesterol ester matrix were stable against recrystallization when stored...

  9. UV curing of nanoparticle reinforced acrylates

    Science.gov (United States)

    Bauer, F.; Flyunt, R.; Czihal, K.; Ernst, H.; Naumov, S.; Buchmeiser, M. R.

    2007-12-01

    To improve the surface hardness of radiation cured acrylate coatings, both silica nanoparticles and alumina particles with a few microns in size have been embedded into acrylate formulations. Regular mixing of nanoparticles into acrylate formulations, however, leads to highly viscous solutions inappropriate for coating procedures. The incompatibility of inorganic fillers and organic polymers can be avoided by surface modification of nanoparticles using trialkoxysilanes, which provide an interface between the two dissimilar materials. Nanoparticles modified by methacryloxypropyltrimethoxysilane (MEMO) and vinyltrimethoxysilane (VTMO), both having polymerisation-active groups, may be crosslinked with the acrylate resin. UV curing of the nanocomposites revealed an unexpected lower reactivity of the vinyl groups of VTMO modified silica compared to MEMO grafted on silica. For VTMO modification, DFT calculations showed a decrease of Mulliken atomic charge for the olefinic carbons pointing to a lower reactivity. For UV cured nano/microhybrid composites, a significant improvement of abrasion resistance was obtained.

  10. UV curing of nanoparticle reinforced acrylates

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, F. [Leibniz-Institut fuer Oberflaechenmodifizierung, Permoserstr. 15, Leipzig D-04318 (Germany)], E-mail: frank.bauer@iom-leipzig.de; Flyunt, R.; Czihal, K. [Leibniz-Institut fuer Oberflaechenmodifizierung, Permoserstr. 15, Leipzig D-04318 (Germany); Ernst, H. [University of Leipzig, Department of Experimental Physics I, Leipzig D-04103 (Germany); Naumov, S. [Leibniz-Institut fuer Oberflaechenmodifizierung, Permoserstr. 15, Leipzig D-04318 (Germany); Buchmeiser, M.R. [Leibniz-Institut fuer Oberflaechenmodifizierung, Permoserstr. 15, Leipzig D-04318 (Germany); University of Leipzig, Institute of Technical Chemistry, Leipzig D-04103 (Germany)

    2007-12-15

    To improve the surface hardness of radiation cured acrylate coatings, both silica nanoparticles and alumina particles with a few microns in size have been embedded into acrylate formulations. Regular mixing of nanoparticles into acrylate formulations, however, leads to highly viscous solutions inappropriate for coating procedures. The incompatibility of inorganic fillers and organic polymers can be avoided by surface modification of nanoparticles using trialkoxysilanes, which provide an interface between the two dissimilar materials. Nanoparticles modified by methacryloxypropyltrimethoxysilane (MEMO) and vinyltrimethoxysilane (VTMO), both having polymerisation-active groups, may be crosslinked with the acrylate resin. UV curing of the nanocomposites revealed an unexpected lower reactivity of the vinyl groups of VTMO modified silica compared to MEMO grafted on silica. For VTMO modification, DFT calculations showed a decrease of Mulliken atomic charge for the olefinic carbons pointing to a lower reactivity. For UV cured nano/microhybrid composites, a significant improvement of abrasion resistance was obtained.

  11. Systematic Equation Formulation

    DEFF Research Database (Denmark)

    Lindberg, Erik

    2007-01-01

    A tutorial giving a very simple introduction to the set-up of the equations used as a model for an electrical/electronic circuit. The aim is to find a method which is as simple and general as possible with respect to implementation in a computer program. The “Modified Nodal Approach”, MNA, and th......, and the “Controlled Source Approach”, CSA, for systematic equation formulation are investigated. It is suggested that the kernel of the P Spice program based on MNA is reprogrammed....

  12. Nanoparticle aggregation controlled by desalting kinetics

    OpenAIRE

    Fresnais, J.; Lavelle, C.; Berret, J. -F.

    2010-01-01

    We report the formation of stable nanoparticle-polymer clusters obtained by electrostatic complexation. The nanoparticles placed under scrutiny are nanoceria (CeO2) coated by short poly(acrylic acid) moieties, whereas the polymers are cationic-neutral block copolymers. The cluster formation was monitored using different formulation pathways, including direct mixing, dialysis, dilution and quenching. In the first process, the hybrids were obtained by mixing stock solutions of polymers and nano...

  13. Protein-directed gold nanoparticles with excellent catalytic activity for 4-nitrophenol reduction.

    Science.gov (United States)

    Liu, Kewei; Han, Lei; Zhuang, Junyang; Yang, Da-Peng

    2017-09-01

    To explore high-performance noble metal nanomaterials for the reduction of the biotoxin 4-nitrophenol (4-NP) in medicine, we developed a green synthesis strategy of bovine serum albumin-stabilized Au nanoparticles (Au@BSA NPs). The as-synthesized Au@BSA NPs were characterized by ultraviolet-visible absorption spectrum, fourier transformed infrared spectroscopy, transmission electron microscopy and dynamic light scattering. The functional bio-nanocomposites showed Au-protein core-shell structure and uniform distribution, and their sizes were dependent on the additive amount of HAuCl 4 . Interestingly, Au@BSA NPs showed remarkable catalytic activity for the reduction of 4-NP into 4-aminophenol in the presence of sodium borohydride. Due to the introduction of Au@BSA NPs, the reduction reaction could be conducted at ambient temperature and pressure without any additional conditions. Moreover, the reduction rate was closely related to the sizes of NPs and reaction temperature, and the catalytic mechanism was verified to follow the pseudo-first-order kinetics. Due to the environmentally friendly synthesis process and green reduction strategy of 4-NP, Au@BSA NPs would show great potential in governance of the biotoxin in medicine. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Drug delivery and formulations.

    Science.gov (United States)

    Breitkreutz, Jörg; Boos, Joachim

    2011-01-01

    Paediatric drug delivery is a major challenge in drug development. Because of the heterogeneous nature of the patient group, ranging from newborns to adolescents, there is a need to use appropriate excipients, drug dosage forms and delivery devices for different age groups. So far, there is a lack of suitable and safe drug formulations for children, especially for the very young and seriously ill patients. The new EU legislation will enforce paediatric clinical trials and drug development. Current advances in paediatric drug delivery include interesting new concepts such as fast-dissolving drug formulations, including orodispersible tablets and oral thin strips (buccal wafers), and multiparticulate dosage forms based on mini-tabletting or pelletization technologies. Parenteral administration is likely to remain the first choice for children in the neonatal period and for emergency cases. Alternative routes of administration include transdermal, pulmonary and nasal drug delivery systems. A few products are already available on the market, but others still need further investigations and clinical proof of concept.

  15. Characterization of Celecoxib-Loaded Solid Lipid Nanoparticles ...

    African Journals Online (AJOL)

    of solid lipid Nanoparticles (SLN) made of cacao butter and curdlan. Eur J Pharm Sci 2005; 24: 199-. 205. 19. Reddy LH, Murthy RS. Etoposide-loaded nanoparticles made from glyceride lipids: formulation, characterization, in vitro drug release, and stability evaluation. AAPS PharmSciTech 2005; 6(2): E158–. E166. 20.

  16. Silver Nanoparticles

    Science.gov (United States)

    Khaydarov, R. R.; Khaydarov, R. A.; Estrin, Y.; Evgrafova, S.; Scheper, T.; Endres, C.; Cho, S. Y.

    The bactericidal effect of silver nanoparticles obtained by a novel electrochemical method on Escherichia coli, Staphylococcus aureus, Aspergillus niger and Penicillium phoeniceum cultures has been studied. The tests conducted have demonstrated that synthesized silver nanoparticles — when added to water paints or cotton fabrics — show a pronounced antibacterial/antifungal effect. It was shown that smaller silver nanoparticles have a greater antibacterial/antifungal efficacy. The paper also provides a review of scientific literature with regard to recent developments in the field of toxicity of silver nanoparticles and its effect on environment and human health.

  17. Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability

    Science.gov (United States)

    Luo, Haitao; Jiang, Bingbing; Li, Bingyun; Li, Zhaoliang; Jiang, Bing-Hua; Chen, Yi Charlie

    2012-01-01

    Ovarian cancer is one of the leading causes of cancer death for women throughout the Western world. Kaempferol, a natural flavonoid, has shown promise in the chemoprevention of ovarian cancer. A common concern about using dietary supplements for chemoprevention is their bioavailability. Nanoparticles have shown promise in increasing the bioavailability of some chemicals. Here we developed five different types of nanoparticles incorporating kaempferol and tested their efficacy in the inhibition of viability of cancerous and normal ovarian cells. We found that positively charged nanoparticle formulations did not lead to a significant reduction in cancer cell viability, whereas nonionic polymeric nanoparticles resulted in enhanced reduction of cancer cell viability. Among the nonionic polymeric nanoparticles, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) nanoparticles incorporating kaempferol led to significant reduction in cell viability of both cancerous and normal cells. Poly(DL-lactic acid-co-glycolic acid) (PLGA) nanoparticles incorporating kaempferol resulted in enhanced reduction of cancer cell viability together with no significant reduction in cell viability of normal cells compared with kaempferol alone. Therefore, both PEO-PPO-PEO and PLGA nanoparticle formulations were effective in reducing cancer cell viability, while PLGA nanoparticles incorporating kaempferol had selective toxicity against cancer cells and normal cells. A PLGA nanoparticle formulation could be advantageous in the prevention and treatment of ovarian cancers. On the other hand, PEO-PPO-PEO nanoparticles incorporating kaempferol were more effective inhibitors of cancer cells, but they also significantly reduced the viability of normal cells. PEO-PPO-PEO nanoparticles incorporating kaempferol may be suitable as a cancer-targeting strategy, which could limit the effects of the nanoparticles on normal cells while retaining their potency against cancer cells. We

  18. Development of novel solid-phase protein formulations

    Science.gov (United States)

    Montalvo Ortiz, Brenda Liz

    profiles and activity during in vitro release. These findings demonstrate that protein particle size is a crucial parameter for protein encapsulation in PLGA devices. Consequently, we developed a simple and effective method to obtain very small protein particles to further improve protein stability in PLGA microspheres. Protein nanoparticles of approximately 200 rim size were obtained by co-lyophilization of HRP with methyl-beta-cyclodextrin (MbetaCD), followed by suspension in ethyl acetate and sonication. We proved that protein integrity was maintained after the nanoparticle formulation. Finally, we encapsulated these protein nanospheres in PLGA microspheres by the s/o/w encapsulation method. The results showed that protein activity was improved when the HRP nanoparticle formulation was encapsulated in PLGA microspheres. In addition, we obtained a reduced initial protein release when the protein was encapsulated as nanoparticles and a linear release profile for more than 30 days. Furthermore, protein activity was maintained for prolonged times during release when compared to the lyophilized HRP formulation. Such improvements were attributed to the decrease in protein particle size. In general, these studies made a contribution in the protein-solid state formulation area. We demonstrate that protein dehydration could be done by a simple method and that particle size could be controlled to obtain the desired protein particle size. Moreover, with the nanoparticle formulation we obtained superior protein stability during encapsulation and release from PLGA microspheres. These new approaches will further increase the use of sustained delivery systems in clinical applications.

  19. PLGA 50: 50 nanoparticles of paclitaxel: Development, in vitro anti ...

    Indian Academy of Sciences (India)

    Clinical administration of paclitaxel is hindered due to its poor solubility, which necessitates the formulation of novel drug delivery systems to deliver such extreme hydrophobic drug. To formulate nanoparticles which makes suitable to deliver hydrophobic drugs effectively (intravenous) with desired pharmacokinetic profile ...

  20. Gold nanoparticles stabilized by chitosan

    International Nuclear Information System (INIS)

    Geraldes, Adriana N.; Oliveira, Maria Jose A.; Silva, Andressa A. da; Leal, Jessica; Batista, Jorge G.S.; Lugao, Ademar B.

    2015-01-01

    In our laboratory has been growing the interest in studying gold nanoparticles and for this reason, the aim of this work is report the first results of the effect of chitosan as stabilizer in gold nanoparticle formulation. AuNPs were synthesized by reducing hydrogen tetrachloroaurate (HAuCl 4 ) using NaBH 4 or gamma irradiation (25kGy) as reduction agent. The chitosan (3 mol L -1 ) was added at 0.5; 1.0 and 1.5 mL. The gold nanoparticles were characterized by UV-Vis absorption spectroscopy, X-ray diffraction (XRD) and Transmission electron microscopy (TEM). Their physical stability was determined using a UV-Vis spectrophotometer over one week during storage at room temperature. Absorption measurements indicated that the plasmon resonance wavelength appears at a wavelength around 530 nm. Has been observed that Chitosan in such quantities were not effective in stabilizing the AuNPs. (author)

  1. Design and Optimization of PLGA-Based Diclofenac Loaded Nanoparticles

    Science.gov (United States)

    Cooper, Dustin L.; Harirforoosh, Sam

    2014-01-01

    Drug based nanoparticle (NP) formulations have gained considerable attention over the past decade for their use in various drug formulations. NPs have been shown to increase bioavailability, decrease side effects of highly toxic drugs, and prolong drug release. Nonsteroidal anti-inflammatory drugs such as diclofenac block cyclooxygenase expression and reduce prostaglandin synthesis, which can lead to several side effects such as gastrointestinal bleeding and renal insufficiency. The aim of this study was to formulate and characterize diclofenac entrapped poly(lactide-co-glycolide) (PLGA) based nanoparticles. Nanoparticles were formulated using an emulsion-diffusion-evaporation technique with varying concentrations of poly vinyl alcohol (PVA) (0.1, 0.25, 0.5, or 1%) or didodecyldimethylammonium bromide (DMAB) (0.1, 0.25, 0.5, 0.75, or 1%) stabilizers centrifuged at 8,800 rpm or 12,000 rpm. The resultant nanoparticles were evaluated based on particle size, zeta potential, and entrapment efficacy. DMAB formulated NPs showed the lowest particle size (108±2.1 nm) and highest zeta potential (−27.71±0.6 mV) at 0.1 and 0.25% respectively, after centrifugation at 12,000 rpm. Results of the PVA based NP formulation showed the smallest particle size (92.4±7.6 nm) and highest zeta potential (−11.14±0.5 mV) at 0.25% and 1% w/v, respectively, after centrifugation at 12,000 rpm. Drug entrapment reached 77.3±3.5% and 80.2±1.2% efficiency with DMAB and PVA formulations, respectively. The results of our study indicate the use of DMAB for increased nanoparticle stability during formulation. Our study supports the effective utilization of PLGA based nanoparticle formulation for diclofenac. PMID:24489896

  2. Intermetallic nanoparticles

    Science.gov (United States)

    Singh, Dileep; Yusufoglu, Yusuf; Timofeeva, Elena; Routbort, Jules

    2015-07-14

    A process for preparing intermetallic nanoparticles of two or more metals is provided. In particular, the process includes the steps: a) dispersing nanoparticles of a first metal in a solvent to prepare a first metal solution, b) forming a reaction mixture with the first metal solution and a reducing agent, c) heating the reaction mixture to a reaction temperature; and d) adding a second metal solution containing a salt of a second metal to the reaction mixture. During this process, intermetallic nanoparticles, which contain a compound with the first and second metals are formed. The intermetallic nanoparticles with uniform size and a narrow size distribution is also provided. An electrochemical device such as a battery with the intermetallic nanoparticles is also provided.

  3. Design and formulation of nano-sized spray dried efavirenz-part I: influence of formulation parameters

    International Nuclear Information System (INIS)

    Katata, Lebogang; Tshweu, Lesego; Naidoo, Saloshnee; Kalombo, Lonji; Swai, Hulda

    2012-01-01

    Efavirenz (EFV) is one of the first-line antiretroviral drugs recommended by the World Health Organisation for treating HIV. It is a hydrophobic drug that suffers from low aqueous solubility (4 μg/mL), which leads to a limited oral absorption and low bioavailability. In order to improve its oral bioavailability, nano-sized polymeric delivery systems are suggested. Spray dried polycaprolactone-efavirenz (PCL-EFV) nanoparticles were prepared by the double emulsion method. The Taguchi method, a statistical design with an L 8 orthogonal array, was implemented to optimise the formulation parameters of PCL-EFV nanoparticles. The types of sugar (lactose or trehalose), surfactant concentration and solvent (dichloromethane and ethyl acetate) were chosen as significant parameters affecting the particle size and polydispersity index (PDI). Small nanoparticles with an average particle size of less than 254 ± 0.95 nm in the case of ethyl acetate as organic solvent were obtained as compared to more than 360 ± 19.96 nm for dichloromethane. In this study, the type of solvent and sugar were the most influencing parameters of the particle size and PDI. Taguchi method proved to be a quick, valuable tool in optimising the particle size and PDI of PCL-EFV nanoparticles. The optimised experimental values for the nanoparticle size and PDI were 217 ± 2.48 nm and 0.093 ± 0.02.

  4. Design and formulation of nano-sized spray dried efavirenz-part I: influence of formulation parameters

    Energy Technology Data Exchange (ETDEWEB)

    Katata, Lebogang, E-mail: lebzakate@yahoo.com; Tshweu, Lesego; Naidoo, Saloshnee; Kalombo, Lonji; Swai, Hulda [Materials Science and Manufacturing, Centre of Polymers and Composites, Council for Scientific and Industrial Research (South Africa)

    2012-11-15

    Efavirenz (EFV) is one of the first-line antiretroviral drugs recommended by the World Health Organisation for treating HIV. It is a hydrophobic drug that suffers from low aqueous solubility (4 {mu}g/mL), which leads to a limited oral absorption and low bioavailability. In order to improve its oral bioavailability, nano-sized polymeric delivery systems are suggested. Spray dried polycaprolactone-efavirenz (PCL-EFV) nanoparticles were prepared by the double emulsion method. The Taguchi method, a statistical design with an L{sub 8} orthogonal array, was implemented to optimise the formulation parameters of PCL-EFV nanoparticles. The types of sugar (lactose or trehalose), surfactant concentration and solvent (dichloromethane and ethyl acetate) were chosen as significant parameters affecting the particle size and polydispersity index (PDI). Small nanoparticles with an average particle size of less than 254 {+-} 0.95 nm in the case of ethyl acetate as organic solvent were obtained as compared to more than 360 {+-} 19.96 nm for dichloromethane. In this study, the type of solvent and sugar were the most influencing parameters of the particle size and PDI. Taguchi method proved to be a quick, valuable tool in optimising the particle size and PDI of PCL-EFV nanoparticles. The optimised experimental values for the nanoparticle size and PDI were 217 {+-} 2.48 nm and 0.093 {+-} 0.02.

  5. Baseline LAW Glass Formulation Testing

    Energy Technology Data Exchange (ETDEWEB)

    Kruger, Albert A. [USDOE Office of River Protection, Richland, WA (United States); Mooers, Cavin [The Catholic University of America, Washington, DC (United States). Vitreous State Lab.; Bazemore, Gina [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Pegg, Ian L. [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Hight, Kenneth [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Lai, Shan Tao [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Buechele, Andrew [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Rielley, Elizabeth [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Gan, Hao [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Muller, Isabelle S. [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Cecil, Richard [The Catholic University of America, Washington, DC (United States). Vitreous State Lab

    2013-06-13

    The major objective of the baseline glass formulation work was to develop and select glass formulations that are compliant with contractual and processing requirements for each of the LAW waste streams. Other objectives of the work included preparation and characterization of glasses with respect to the properties of interest, optimization of sulfate loading in the glasses, evaluation of ability to achieve waste loading limits, testing to demonstrate compatibility of glass melts with melter materials of construction, development of glass formulations to support ILAW qualification activities, and identification of glass formulation issues with respect to contract specifications and processing requirements.

  6. Computer Optimization of Biodegradable Nanoparticles Fabricated by Dispersion Polymerization

    Directory of Open Access Journals (Sweden)

    Emmanuel O. Akala

    2015-12-01

    Full Text Available Quality by design (QbD in the pharmaceutical industry involves designing and developing drug formulations and manufacturing processes which ensure predefined drug product specifications. QbD helps to understand how process and formulation variables affect product characteristics and subsequent optimization of these variables vis-à-vis final specifications. Statistical design of experiments (DoE identifies important parameters in a pharmaceutical dosage form design followed by optimizing the parameters with respect to certain specifications. DoE establishes in mathematical form the relationships between critical process parameters together with critical material attributes and critical quality attributes. We focused on the fabrication of biodegradable nanoparticles by dispersion polymerization. Aided by a statistical software, d-optimal mixture design was used to vary the components (crosslinker, initiator, stabilizer, and macromonomers to obtain twenty nanoparticle formulations (PLLA-based nanoparticles and thirty formulations (poly-ɛ-caprolactone-based nanoparticles. Scheffe polynomial models were generated to predict particle size (nm, zeta potential, and yield (% as functions of the composition of the formulations. Simultaneous optimizations were carried out on the response variables. Solutions were returned from simultaneous optimization of the response variables for component combinations to (1 minimize nanoparticle size; (2 maximize the surface negative zeta potential; and (3 maximize percent yield to make the nanoparticle fabrication an economic proposition.

  7. Computer Optimization of Biodegradable Nanoparticles Fabricated by Dispersion Polymerization.

    Science.gov (United States)

    Akala, Emmanuel O; Adesina, Simeon; Ogunwuyi, Oluwaseun

    2015-12-22

    Quality by design (QbD) in the pharmaceutical industry involves designing and developing drug formulations and manufacturing processes which ensure predefined drug product specifications. QbD helps to understand how process and formulation variables affect product characteristics and subsequent optimization of these variables vis-à-vis final specifications. Statistical design of experiments (DoE) identifies important parameters in a pharmaceutical dosage form design followed by optimizing the parameters with respect to certain specifications. DoE establishes in mathematical form the relationships between critical process parameters together with critical material attributes and critical quality attributes. We focused on the fabrication of biodegradable nanoparticles by dispersion polymerization. Aided by a statistical software, d-optimal mixture design was used to vary the components (crosslinker, initiator, stabilizer, and macromonomers) to obtain twenty nanoparticle formulations (PLLA-based nanoparticles) and thirty formulations (poly-ɛ-caprolactone-based nanoparticles). Scheffe polynomial models were generated to predict particle size (nm), zeta potential, and yield (%) as functions of the composition of the formulations. Simultaneous optimizations were carried out on the response variables. Solutions were returned from simultaneous optimization of the response variables for component combinations to (1) minimize nanoparticle size; (2) maximize the surface negative zeta potential; and (3) maximize percent yield to make the nanoparticle fabrication an economic proposition.

  8. Computer Optimization of Biodegradable Nanoparticles Fabricated by Dispersion Polymerization

    Science.gov (United States)

    Akala, Emmanuel O.; Adesina, Simeon; Ogunwuyi, Oluwaseun

    2015-01-01

    Quality by design (QbD) in the pharmaceutical industry involves designing and developing drug formulations and manufacturing processes which ensure predefined drug product specifications. QbD helps to understand how process and formulation variables affect product characteristics and subsequent optimization of these variables vis-à-vis final specifications. Statistical design of experiments (DoE) identifies important parameters in a pharmaceutical dosage form design followed by optimizing the parameters with respect to certain specifications. DoE establishes in mathematical form the relationships between critical process parameters together with critical material attributes and critical quality attributes. We focused on the fabrication of biodegradable nanoparticles by dispersion polymerization. Aided by a statistical software, d-optimal mixture design was used to vary the components (crosslinker, initiator, stabilizer, and macromonomers) to obtain twenty nanoparticle formulations (PLLA-based nanoparticles) and thirty formulations (poly-ɛ-caprolactone-based nanoparticles). Scheffe polynomial models were generated to predict particle size (nm), zeta potential, and yield (%) as functions of the composition of the formulations. Simultaneous optimizations were carried out on the response variables. Solutions were returned from simultaneous optimization of the response variables for component combinations to (1) minimize nanoparticle size; (2) maximize the surface negative zeta potential; and (3) maximize percent yield to make the nanoparticle fabrication an economic proposition. PMID:26703678

  9. PLA micro- and nano-particles.

    Science.gov (United States)

    Lee, Byung Kook; Yun, Yeonhee; Park, Kinam

    2016-12-15

    Poly(d,l-lactic acid) (PLA) has been widely used for various biomedical applications for its biodegradable, biocompatible, and nontoxic properties. Various methods, such as emulsion, salting out, and precipitation, have been used to make better PLA micro- and nano-particle formulations. They are widely used as controlled drug delivery systems of therapeutic molecules, including proteins, genes, vaccines, and anticancer drugs. Even though PLA-based particles have challenges to overcome, such as low drug loading capacity, low encapsulation efficiency, and terminal sterilization, continuous innovations in particulate formulations will lead to development of clinically useful formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Nanoparticle Additives for Multiphase Systems: Synthesis, Formulation and Characterization

    Science.gov (United States)

    2012-01-01

    solid, the nanofluid has the potential to improve local heat transfer while reducing friction and providing protection from wear. Nanofluids with... protect metal surfaces from wear and corrosion, transfer heat from critical parts and suspend particulate impurities, among other things. As the...surfaces in cleanability and surface drag, especially for products such as eyeglass lenses, displays for consumer electronics, architectural windows

  11. Surface interactions between gold nanoparticles and biochar

    Science.gov (United States)

    Engineered nanomaterials are directly applied to agricultural soils as a part of pesticide/fertilize formulations and sludge/manure amendments. Yet, no prior reports are available on the extent and reversibility of gold nanoparticles (nAu) retention by soil components including charcoal black carbo...

  12. Methotrexate-loaded biodegradable nanoparticles: preparation ...

    Indian Academy of Sciences (India)

    The prepared nanoparticles were evaluated for physicochemical properties such as particle size, zeta potential, release studies, etc and also evaluated for its in vitro cytotoxic potential against U-343 MGa human neuronal glioblastoma cells. Particle size of optimized formulation was < 200 nm. There was a considerable ...

  13. Saltstone Clean Cap Formulation

    Energy Technology Data Exchange (ETDEWEB)

    Langton, C

    2005-04-22

    The current operation strategy for using Saltstone Vault 4 to receive 0.2 Ci/gallon salt solution waste involves pouring a clean grout layer over the radioactive grout prior to initiating pour into another cell. This will minimize the radiating surface area and reduce the dose rate at the vault and surrounding area. The Clean Cap will be used to shield about four feet of Saltstone poured into a Z-Area vault cell prior to moving to another cell. The minimum thickness of the Clean Cap layer will be determined by the cesium concentration and resulting dose levels and it is expected to be about one foot thick based on current calculations for 0.1 Ci Saltstone that is produced in the Saltstone process by stabilization of 0.2 Ci salt solution. This report documents experiments performed to identify a formulation for the Clean Cap. Thermal transient calculations, adiabatic temperature rise measurements, pour height, time between pour calculations and shielding calculations were beyond the scope and time limitations of this study. However, data required for shielding calculations (composition and specific gravity) are provided for shielding calculations. The approach used to design a Clean Cap formulation was to produce a slurry from the reference premix (10/45/45 weight percent cement/slag/fly ash) and domestic water that resembled as closely as possible the properties of the Saltstone slurry. In addition, options were investigated that may offer advantages such as less bleed water and less heat generation. The options with less bleed water required addition of dispersants. The options with lower heat contained more fly ash and less slag. A mix containing 10/45/45 weight percent cement/slag/fly ash with a water to premix ratio of 0.60 is recommended for the Clean Cap. Although this mix may generate more than 3 volume percent standing water (bleed water), it has rheological, mixing and flow properties that are similar to previously processed Saltstone. The recommended

  14. Saltstone Clean Cap Formulation

    International Nuclear Information System (INIS)

    Langton, C

    2005-01-01

    The current operation strategy for using Saltstone Vault 4 to receive 0.2 Ci/gallon salt solution waste involves pouring a clean grout layer over the radioactive grout prior to initiating pour into another cell. This will minimize the radiating surface area and reduce the dose rate at the vault and surrounding area. The Clean Cap will be used to shield about four feet of Saltstone poured into a Z-Area vault cell prior to moving to another cell. The minimum thickness of the Clean Cap layer will be determined by the cesium concentration and resulting dose levels and it is expected to be about one foot thick based on current calculations for 0.1 Ci Saltstone that is produced in the Saltstone process by stabilization of 0.2 Ci salt solution. This report documents experiments performed to identify a formulation for the Clean Cap. Thermal transient calculations, adiabatic temperature rise measurements, pour height, time between pour calculations and shielding calculations were beyond the scope and time limitations of this study. However, data required for shielding calculations (composition and specific gravity) are provided for shielding calculations. The approach used to design a Clean Cap formulation was to produce a slurry from the reference premix (10/45/45 weight percent cement/slag/fly ash) and domestic water that resembled as closely as possible the properties of the Saltstone slurry. In addition, options were investigated that may offer advantages such as less bleed water and less heat generation. The options with less bleed water required addition of dispersants. The options with lower heat contained more fly ash and less slag. A mix containing 10/45/45 weight percent cement/slag/fly ash with a water to premix ratio of 0.60 is recommended for the Clean Cap. Although this mix may generate more than 3 volume percent standing water (bleed water), it has rheological, mixing and flow properties that are similar to previously processed Saltstone. The recommended

  15. Surface decorated Fe3O4 nanoparticles for magnetic hyperthermia

    Science.gov (United States)

    Gawali, Santosh L.; Barick, K. C.; Hassan, P. A.

    2017-05-01

    Magnetic nanoparticles have been widely investigated for their great potential in several biomedical applications such as magnetic hyperthermia, drug delivery and magnetic resonance imaging (MRI). We have developed a formulation in which the surface of Fe3O4 magnetic nanoparticles is decorated with succinic acid (SA) to provide enhanced colloidal stability in biological fluids while preserving their optimal magnetic properties. The successful surface decoration of particles with SA is evident from FTIR, TGA, DLS and zeta-potential measurements. XRD and TEM analysis revealed the formation of inverse spinel Fe3O4 nanoparticles of average size 10 nm. Our induction heating studies exhibited the excellent heating efficacy of these nanoparticles under applied AC magnetic field. The heating ability was found to be strongly dependent on the concentration of particles in magnetic suspension and applied AC magnetic field. Specifically, a novel water-dispersible surface decorated Fe3O4 nanoparticles formulation was developed for magnetic hyperthermia.

  16. Fluoride loaded polymeric nanoparticles for dental delivery.

    Science.gov (United States)

    Nguyen, Sanko; Escudero, Carlos; Sediqi, Nadia; Smistad, Gro; Hiorth, Marianne

    2017-06-15

    The overall aim of the present paper was to develop fluoride loaded nanoparticles based on the biopolymers chitosan, pectin, and alginate, for use in dental delivery. First, the preparation of nanoparticles in the presence of sodium fluoride (NaF) as the active ingredient by ionic gelation was investigated followed by an evaluation of their drug entrapment and release properties. Chitosan formed stable, spherical, and monodisperse nanoparticles in the presence of NaF and tripolyphoshate as the crosslinker, whereas alginate and pectin were not able to form any definite nanostructures in similar conditions. The fluoride loading capacity was found to be 33-113ppm, and the entrapment efficiency 3.6-6.2% for chitosan nanoparticles prepared in 0.2-0.4% (w/w) NaF, respectively. A steady increase in the fluoride release was observed for chitosan nanoparticles prepared in 0.2% NaF both in pH5 and 7 until it reached a maximum at time point 4h and maintained at this level for at least 24h. Similar profiles were observed for formulations prepared in 0.4% NaF; however the fluoride was released at a higher level at pH5. The low concentration, but continuous delivery of fluoride from the chitosan nanoparticles, with possible expedited release in acidic environment, makes these formulations highly promising as dental delivery systems in the protection against caries development. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Ultrasound mediated nanoparticle drug delivery

    Science.gov (United States)

    Mullin, Lee B.

    Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems

  18. Kinetics of laser irradiated nanoparticles cloud

    Science.gov (United States)

    Mishra, S. K.; Upadhyay Kahaly, M.; Misra, Shikha

    2018-02-01

    A comprehensive kinetic model describing the complex kinetics of a laser irradiated nanoparticle ensemble has been developed. The absorbed laser radiation here serves dual purpose, viz., photoenhanced thermionic emission via rise in its temperature and direct photoemission of electrons. On the basis of mean charge theory along with the equations for particle (electron) and energy flux balance over the nanoparticles, the transient processes of charge/temperature evolution over its surface and mass diminution on account of the sublimation (phase change) process have been elucidated. Using this formulation phenomenon of nanoparticle charging, its temperature rise to the sublimation point, mass ablation, and cloud disintegration have been investigated; afterwards, typical timescales of disintegration, sublimation and complete evaporation in reference to a graphite nanoparticle cloud (as an illustrative case) have been parametrically investigated. Based on a numerical analysis, an adequate parameter space describing the nanoparticle operation below the sublimation temperature, in terms of laser intensity, wavelength and nanoparticle material work function, has been identified. The cloud disintegration is found to be sensitive to the nanoparticle charging through photoemission; as a consequence, it illustrates that radiation operating below the photoemission threshold causes disintegration in the phase change state, while above the threshold, it occurs with the onset of surface heating.

  19. Tactile friction of topical formulations.

    Science.gov (United States)

    Skedung, L; Buraczewska-Norin, I; Dawood, N; Rutland, M W; Ringstad, L

    2016-02-01

    The tactile perception is essential for all types of topical formulations (cosmetic, pharmaceutical, medical device) and the possibility to predict the sensorial response by using instrumental methods instead of sensory testing would save time and cost at an early stage product development. Here, we report on an instrumental evaluation method using tactile friction measurements to estimate perceptual attributes of topical formulations. Friction was measured between an index finger and an artificial skin substrate after application of formulations using a force sensor. Both model formulations of liquid crystalline phase structures with significantly different tactile properties, as well as commercial pharmaceutical moisturizing creams being more tactile-similar, were investigated. Friction coefficients were calculated as the ratio of the friction force to the applied load. The structures of the model formulations and phase transitions as a result of water evaporation were identified using optical microscopy. The friction device could distinguish friction coefficients between the phase structures, as well as the commercial creams after spreading and absorption into the substrate. In addition, phase transitions resulting in alterations in the feel of the formulations could be detected. A correlation was established between skin hydration and friction coefficient, where hydrated skin gave rise to higher friction. Also a link between skin smoothening and finger friction was established for the commercial moisturizing creams, although further investigations are needed to analyse this and correlations with other sensorial attributes in more detail. The present investigation shows that tactile friction measurements have potential as an alternative or complement in the evaluation of perception of topical formulations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Preformulation and formulation development of a bioactive nitroaromatic compound

    Science.gov (United States)

    Sena, Camila F. A.; Apolinário, Lívia S.; Duarte, Jaqueline A.; dos Santos, Giovanna C.; Monteiro, Liziane O. F.; de Oliveira, Mônica C.; Leite, Elaine A.; de Oliveira, Renata B.

    2017-11-01

    The N-(butanoyloxyethyl)-4-(chloromethyl)-3-nitrobenzamide (BNB) is a nitroaromatic derivative with significant antitumor activity. Preformulation, forced degradation (distilled water, acid and base hydrolysis, oxidation, and light), and formulation studies were performed to investigate the chemical behavior of the molecule, the physicochemical properties, and the impact of formulation variables. Pharmacokinetic properties for BNB were estimated in silico. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) containing BNB were developed by a hot melt homogenization method for parenteral administration. Degradation studies demonstrated that this compound is sensitive to hydrolysis. BNB was predicted to have a favorable absorption, distribution, metabolism, and excretion profile. The nanocarriers developed were characterized for particle size (PS = 61 to 85 nm), polydispersity index (PI studies indicated that BNB (inhibitory concentration (IC50) 21.8 μM) and BNB-loaded NLC (IC50 33.7 μM) showed moderate cytotoxicity against breast cancer cell line. Blank formulations did not induce cytotoxicity and BNB-loaded SLN was able to potentiate the action of BNB (lC50 12.4 μM). BNB is a promising antitumor agent and it is possible to modulate its activity based on the particle size of the formulation.

  1. Nanoparticle standards

    Energy Technology Data Exchange (ETDEWEB)

    Havrilla, George Joseph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-12-08

    We will purchase a COTS materials printer and adapt it for solution printing of known elemental concentration solutions. A methodology will be developed to create deposits of known mass in known locations on selected substrates. The deposits will be characterized for deposited mass, physical morphology, thickness and uniformity. Once an acceptable methodology has been developed and validated, we will create round robin samples to be characterized by LGSIMS instruments at LANL, PNNL and NIST. We will demonstrate the feasibility of depositing nanoparticles in known masses with the goal of creating separated nanoparticles in known locations.

  2. Abuse-deterrent Opioid Formulations.

    Science.gov (United States)

    Litman, Ronald S; Pagán, Olivia H; Cicero, Theodore J

    2017-12-18

    Abuse-deterrent opioid formulations have been suggested as one way to decrease the abuse, addiction, and overdose of orally prescribed opioids. Ten oral opioid formulations have received abuse-deterrent labeling by the U.S. Food and Drug Administration (FDA). Their properties consist of physical and/or chemical means by which the pills resist manipulation and create a barrier to unintended administration, such as chewing, nasal snorting, smoking, and intravenous injection. In this review, we describe the mechanisms of abuse-deterrent technology, the types of premarketing studies required for FDA approval, the pharmacology of the currently approved abuse-deterrent opioid formulations, and the evidence for and against their influence on opioid abuse. We conclude that there is currently insufficient evidence to indicate that the availability of abuse-deterrent opioid formulations has altered the trajectory of opioid overdose and addiction; however, postmarketing studies are in their infancy, and novel deterrent formulations are continually being developed and submitted for marketing approval.

  3. Budesonide nanoparticle agglomerates as dry powder aerosols with rapid dissolution

    Science.gov (United States)

    El-Gendy, Nashwa; Gorman, Eric M.; Munson, Eric J.; Berkland, Cory

    2015-01-01

    Purpose Nanoparticle technology represents an attractive approach for formulating poorly water soluble pulmonary medicines. Unfortunately, nanoparticle suspensions used in nebulizers or metered dose inhalers often suffer from physical instability in the form of uncontrolled agglomeration or Ostwald ripening. In addition, processing such suspensions into dry powders can yield broad particle size distributions. To address these encumbrances, a controlled nanoparticle flocculation process has been developed. Method Nanosuspensions of the poorly water soluble drug budesonide were prepared by dissolving the drug in organic solvent containing surfactants followed by rapid solvent extraction in water. Different surfactants were employed to control the size and surface charge of the precipitated nanoparticles. Nanosuspensions were flocculated using leucine and lyophilized. Results Selected budesonide nanoparticle suspensions exhibited an average particle size ranging from ~160–230 nm, high yield and high drug content. Flocculated nanosuspensions produced micron-sized agglomerates. Freeze-drying the nanoparticle agglomerates yielded dry powders with desirable aerodynamic properties for inhalation therapy. In addition, the dissolution rates of dried nanoparticle agglomerate formulations were significantly faster than that of stock budesonide. Conclusion The results of this study suggest that nanoparticle agglomerates possess the microstructure desired for lung deposition and the nanostructure to facilitate rapid dissolution of poorly water soluble drugs. PMID:19130469

  4. Formulations of Amlodipine: A Review

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Sheraz

    2016-01-01

    Full Text Available Amlodipine (AD is a calcium channel blocker that is mainly used in the treatment of hypertension and angina. However, latest findings have revealed that its efficacy is not only limited to the treatment of cardiovascular diseases as it has shown to possess antioxidant activity and plays an important role in apoptosis. Therefore, it is also employed in the treatment of cerebrovascular stroke, neurodegenerative diseases, leukemia, breast cancer, and so forth either alone or in combination with other drugs. AD is a photosensitive drug and requires protection from light. A number of workers have tried to formulate various conventional and nonconventional dosage forms of AD. This review highlights all the formulations that have been developed to achieve maximum stability with the desired therapeutic action for the delivery of AD such as fast dissolving tablets, floating tablets, layered tablets, single-pill combinations, capsules, oral and transdermal films, suspensions, emulsions, mucoadhesive microspheres, gels, transdermal patches, and liposomal formulations.

  5. (shell) nanoparticles

    Indian Academy of Sciences (India)

    nanoparticles the quasistatic approximation is not appropriate and Mie theory illustrates SPR due to dipole and quadrupole in extinction ... The time-dependent local density approximation (TDLDA) [19] .... satile technique for determining the optical properties of nanoshells or any other spherical particles of any dimension.

  6. Radiosensitizing Silica Nanoparticles encapsulating Docetaxel for Treatment of Prostate Cancer

    OpenAIRE

    Belz, Jodi; Castilla-Ojo, Noelle; Sridhar, Srinivas; Kumar, Rajiv

    2017-01-01

    The applications of nanoparticles in oncology include enhanced drug delivery, efficient tumor targeting, treatment monitoring and diagnostics. The ‘theranostic properties’ associated with nanoparticles have shown enhanced delivery of chemotherapeutic drugs with superior imaging capabilities and minimal toxicities. In conventional chemotherapy, only a fraction of the administered drug reaches the tumor site or cancer cells. For successful translation of these formulations, it is imperative to ...

  7. Optical bistability and multistability in polaritonic materials doped with nanoparticles

    International Nuclear Information System (INIS)

    Wang, Zhiping; Yu, Benli

    2014-01-01

    We investigate the optical bistability and multistability in polaritonic materials doped with nanoparticles inside an optical ring cavity. It is found that the optical bistability and multistability can be easily controlled by adjusting the corresponding parameters of the system properly. The effect of the dipole–dipole interaction has also been included in the formulation, which leads to interesting phenomena. Our scheme opens up the possibility of controling the optical bistability and multistability in polaritonic materials doped with nanoparticles. (letter)

  8. Supramolecular curcumin-barium prodrugs for formulating with ceramic particles.

    Science.gov (United States)

    Kamalasanan, Kaladhar; Anupriya; Deepa, M K; Sharma, Chandra P

    2014-10-01

    A simple and stable curcumin-ceramic combined formulation was developed with an aim to improve curcumin stability and release profile in the presence of reactive ceramic particles for potential dental and orthopedic applications. For that, curcumin was complexed with barium (Ba(2+)) to prepare curcumin-barium (BaCur) complex. Upon removal of the unbound curcumin and Ba(2+) by dialysis, a water-soluble BaCur complex was obtained. The complex was showing [M+1](+) peak at 10,000-20,000 with multiple fractionation peaks of MALDI-TOF-MS studies, showed that the complex was a supramolecular multimer. The (1)H NMR and FTIR studies revealed that, divalent Ba(2+) interacted predominantly through di-phenolic groups of curcumin to form an end-to-end complex resulted in supramolecular multimer. The overall crystallinity of the BaCur was lower than curcumin as per XRD analysis. The complexation of Ba(2+) to curcumin did not degrade curcumin as per HPLC studies. The fluorescence spectrum was blue shifted upon Ba(2+) complexation with curcumin. Monodisperse nanoparticles with size less than 200dnm was formed, out of the supramolecular complex upon dialysis, as per DLS, and upon loading into pluronic micelles the size was remaining in similar order of magnitude as per DLS and AFM studies. Stability of the curcumin was improved greater than 50% after complexation with Ba(2+) as per UV/Vis spectroscopy. Loading of the supramloecular nanoparticles into pluronic micelles had further improved the stability of curcumin to approx. 70% in water. These BaCur supramolecule nanoparticles can be considered as a new class of prodrugs with improved solubility and stability. Subsequently, ceramic nanoparticles with varying chemical composition were prepared for changing the material surface reactivity in terms of the increase in, degradability, surface pH and protein adsorption. Further, these ceramic particles were combined with curcumin prodrug formulations and optimized the curcumin release

  9. Nanoparticles laden in situ gel for sustained ocular drug delivery

    Directory of Open Access Journals (Sweden)

    Himanshu Gupta

    2013-01-01

    Full Text Available Proper availability of drug on to corneal surface is a challenging task. However, due to ocular physiological barriers, conventional eye drops display poor ocular bioavailability of drugs (< 1%. To improve precorneal residence time and ocular penetration, earlier our group developed and evaluated in situ gel and nanoparticles for ocular delivery. In interest to evaluate the combined effect of in situ gel and nanoparticles on ocular retention, we combined them. We are the first to term this combination as "nanoparticle laden in situ gel", that is, poly lactic co glycolic acid nanoparticle incorporated in chitosan in situ gel for sparfloxacin ophthalmic delivery. The formulation was tested for various physicochemical properties. It showed gelation pH near pH 7.2. The observation of acquired gamma camera images showed good retention over the entire precorneal area for sparfloxacin nanoparticle laden in situ gel (SNG as compared to marketed formulation. SNG formulation cleared at a very slow rate and remained at corneal surface for longer duration as no radioactivity was observed in systemic circulation. The developed formulation was found to be better in combination and can go up to the clinical evaluation and application.

  10. Preparation of nanoparticles by continuous-flow microfluidics

    International Nuclear Information System (INIS)

    Jahn, Andreas; Reiner, Joseph E.; Vreeland, Wyatt N.; DeVoe, Don L.; Locascio, Laurie E.; Gaitan, Michael

    2008-01-01

    We review a variety of micro- and nanoparticle formulations produced with microfluidic methods. A diverse variety of approaches to generate microscale and nanoscale particles has been reported. Here we emphasize the use of microfluidics, specifically microfluidic systems that operate in a continuous flow mode, thereby allowing continuous generation of desired particle formulations. The generation of semiconductor quantum dots, metal colloids, emulsions, and liposomes is considered. To emphasize the potential benefits of the continuous-flow microfluidic methodology for nanoparticle generation, preliminary data on the size distribution of liposomes formed using the microfluidic approach is compared to the traditional bulk alcohol injection method.

  11. Hamiltonian formulation of the supermembrane

    International Nuclear Information System (INIS)

    Bergshoeff, E.; Sezgin, E.; Tanii, Y.

    1987-06-01

    The Hamiltonian formulation of the supermembrane theory in eleven dimensions is given. The covariant split of the first and second class constraints is exhibited, and their Dirac brackets are computed. Gauge conditions are imposed in such a way that the reparametrizations of the membrane with divergence free 2-vectors are unfixed. (author). 10 refs

  12. Curcumin nanodisks: formulation and characterization

    OpenAIRE

    Ghosh, Mistuni; Singh, Amareshwar T. K.; Xu, Wenwei; Sulchek, Todd; Gordon, Leo I.; Ryan, Robert O.

    2010-01-01

    Nanodisks (ND) are nanoscale, disk-shaped phospholipid bilayers whose edge is stabilized by apolipoproteins. In the present study, ND were formulated with the bioactive polyphenol, curcumin, at a 6:1 phospholipid:curcumin molar ratio. Atomic force microscopy revealed that curcumin-ND are particles with diameters

  13. Alternate formulations of classical electrodynamics

    International Nuclear Information System (INIS)

    Beil, R.G.

    1975-01-01

    The Lorentz--Dirac, Wheeler--Feynman, and Synge formulations of classical electrodynamics are compared with regard to their equations of motion for charged particles and their treatment of radiation. It is found that the less familiar Synge theory offers a viable alternate to the other two, since it is theoretically consistent and predicts results not at variance with experiment

  14. Case Formulation in TADS CBT

    Science.gov (United States)

    Rogers, Gregory M.; Reinecke, Mark A.; Curry, John F.

    2005-01-01

    For the Treatment for Adolescents With Depression Study (TADS), a cognitive-behavioral therapy (CBT) manual was developed with the aim of balancing standardization and flexibility. In this article, we describe the manual's case formulation procedures, which served as one major mechanism of flexibility in TADS CBT. We first describe the essential…

  15. Covariant Formulation of Hooke's Law.

    Science.gov (United States)

    Gron, O.

    1981-01-01

    Introducing a four-vector strain and a four-force stress, Hooke's law is written as a four-vector equation. This formulation is shown to clarify seemingly paradoxical results in connection with uniformly accelerated motion, and rotational motion with angular acceleration. (Author/JN)

  16. On Hamiltonian formulation of cosmologies

    Indian Academy of Sciences (India)

    This opens up the way to the usual technique of quantization. Elbaz et al [4] have applied this method to the Hamiltonian formulation of FRW cosmological equations. This note presents a generalization of this approach to a variety of cosmologies. A general Schrödinger wave equation has been derived and exact solutions ...

  17. Hydrogel Containing Nanoparticle-Stabilized Liposomes for Topical Antimicrobial Delivery

    Science.gov (United States)

    2015-01-01

    Adsorbing small charged nanoparticles onto the outer surfaces of liposomes has become an effective strategy to stabilize liposomes against fusion prior to “seeing” target bacteria, yet allow them to fuse with the bacteria upon arrival at the infection sites. As a result, nanoparticle-stabilized liposomes have become an emerging drug delivery platform for treatment of various bacterial infections. To facilitate the translation of this platform for clinical tests and uses, herein we integrate nanoparticle-stabilized liposomes with hydrogel technology for more effective and sustained topical drug delivery. The hydrogel formulation not only preserves the structural integrity of the nanoparticle-stabilized liposomes, but also allows for controllable viscoeleasticity and tunable liposome release rate. Using Staphylococcus aureus bacteria as a model pathogen, we demonstrate that the hydrogel formulation can effectively release nanoparticle-stabilized liposomes to the bacterial culture, which subsequently fuse with bacterial membrane in a pH-dependent manner. When topically applied onto mouse skin, the hydrogel formulation does not generate any observable skin toxicity within a 7-day treatment. Collectively, the hydrogel containing nanoparticle-stabilized liposomes hold great promise for topical applications against various microbial infections. PMID:24483239

  18. Electrostatic complexation of polyelectrolyte and magnetic nanoparticles: from wild clustering to controllable magnetic wires

    OpenAIRE

    Yan, Minhao; Qu, Li; Fan, Jiangxia; Ren, Yong

    2014-01-01

    We present the electrostatic complexation between polyelectrolytes and charged nanoparticles. The nanoparticles in solution are γ-Fe2O3 (maghemite) spheres with 8.3 nm diameter and anionic surface charges. The complexation was monitored using three different formulation pathways such as direct mixing, dilution, and dialysis. In the first process, the hybrids were obtained by mixing stock solutions of polymers and nanoparticles. A ‘destabilization state’ with sharp and intense maximum aggregat...

  19. Biomaterials for nanoparticle vaccine delivery systems.

    Science.gov (United States)

    Sahdev, Preety; Ochyl, Lukasz J; Moon, James J

    2014-10-01

    Subunit vaccination benefits from improved safety over attenuated or inactivated vaccines, but their limited capability to elicit long-lasting, concerted cellular and humoral immune responses is a major challenge. Recent studies have demonstrated that antigen delivery via nanoparticle formulations can significantly improve immunogenicity of vaccines due to either intrinsic immunostimulatory properties of the materials or by co-entrapment of molecular adjuvants such as Toll-like receptor agonists. These studies have collectively shown that nanoparticles designed to mimic biophysical and biochemical cues of pathogens offer new exciting opportunities to enhance activation of innate immunity and elicit potent cellular and humoral immune responses with minimal cytotoxicity. In this review, we present key research advances that were made within the last 5 years in the field of nanoparticle vaccine delivery systems. In particular, we focus on the impact of biomaterials composition, size, and surface charge of nanoparticles on modulation of particle biodistribution, delivery of antigens and immunostimulatory molecules, trafficking and targeting of antigen presenting cells, and overall immune responses in systemic and mucosal tissues. This review describes recent progresses in the design of nanoparticle vaccine delivery carriers, including liposomes, lipid-based particles, micelles and nanostructures composed of natural or synthetic polymers, and lipid-polymer hybrid nanoparticles.

  20. Peptide-Loaded Solid Lipid Nanoparticles Prepared through Coacervation Technique

    Directory of Open Access Journals (Sweden)

    Marina Gallarate

    2011-01-01

    Full Text Available Stearic acid solid lipid nanoparticles were prepared according to a new technique, called coacervation. The main goal of this experimental work was the entrapment of peptide drugs into SLN, which is a difficult task, since their chemical characteristics (molecular weight, hydrophilicity, and stability hamper peptide-containing formulations. Insulin and leuprolide, chosen as model peptide drugs, were encapsulated within nanoparticles after hydrophobic ion pairing with anionic surfactants. Peptide integrity was maintained after encapsulation, and nanoparticles can act in vitro as a sustained release system for peptide.

  1. The design of pH-sensitive chitosan-based formulations for gastrointestinal delivery.

    Science.gov (United States)

    Du, Hongliang; Liu, Mengrui; Yang, Xiaoye; Zhai, Guangxi

    2015-08-01

    Chitosan, a nontoxic and biocompatible polysaccharide, has been widely explored for the gastrointestinal delivery of drugs, proteins, peptides and genes for different therapeutic purposes. Because a pH gradient exists in the gastrointestinal tract, chitosan-based formulations in response to specific pH conditions, such as the low pH in the stomach and a high pH in the intestine, have been developed as a general strategy for disease diagnosis and therapy. Tailored pH-responsive drug release in the gastrointestinal tract can be achieved with various chitosan-based formulations such as nanoparticles, microspheres, hydrogels and nanocomposites. This review focuses on the most recent development of chitosan-based pH-sensitive formulations for gastrointestinal delivery, covering various types of chitosan-based formulations, their pH-responsive mechanisms and biomedical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Biological synthesis of silver nanoparticles by using Viola serpens extract

    Directory of Open Access Journals (Sweden)

    Anu Kumar

    2016-03-01

    Full Text Available Objective: To formulate a biological approach for the biological synthesis of silver nanoparticles using aqueous extracts of leaves of Viola serpens which is considered as a ecofriendly method as it does not include any harmful chemicals. Methods: The synthesized silver nanoparticles were characterized by using UV-vis spectroscopy analysis, scanning electron microscopy analysis and X-ray diffraction analysis. Results: Scanning electron microscopy analysis study revealed that synthesized silver nanoparticles were of an average size of 80–90 nm. Crystalline nature of synthesized silver nanoparticles was confirmed by X-ray diffraction analysis. Conclusions: The leaves of Viola serpens can be a potent source for the biological synthesis of silver nanoparticles. The outcome of the study can lead to the development of a novel drug for biomedical field.

  3. Amikacin loaded PLGA nanoparticles against Pseudomonas aeruginosa.

    Science.gov (United States)

    Sabaeifard, Parastoo; Abdi-Ali, Ahya; Soudi, Mohammad Reza; Gamazo, Carlos; Irache, Juan Manuel

    2016-10-10

    Amikacin is a very effective aminoglycoside antibiotic but according to its high toxicity, the use of this antibiotic has been limited. The aim of this study was to formulate and characterize amikacin loaded PLGA nanoparticles. Nanoparticles were synthetized using a solid-in-oil-in-water emulsion technique with different ratio of PLGA 50:50 (Resomer 502H) to drug (100:3.5, 80:3.5 and 60:3.5), two different concentrations of stabilizer (pluronic F68) (0.5% or 1%) and varied g forces to recover the final products. The most efficient formulation based on drug loading (26.0±1.3μg/mg nanoparticle) and encapsulation efficiency (76.8±3.8%) was the one obtained with 100:3.5 PLGA:drug and 0.5% luronic F68, recovered by 20,000×g for 20min. Drug release kinetic study indicated that about 50% of the encapsulated drug was released during the first hour of incubation in phospahte buffer, pH7.4, 37°C, 120rpm. Using different cell viability/cytotoxicity assays, the optimized formulation showed no toxicity against RAW macrophages after 2 and 24h of exposure. Furthermore, released drug was active and maintained its bactericidal activity against Pseudomonas aeruginosa in vitro. These results support the effective utilization of the PLGA nanoparticle formulation for amikacin in further in vivo studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Food protein-based phytosterol nanoparticles: fabrication and characterization.

    Science.gov (United States)

    Cao, Wen-Jun; Ou, Shi-Yi; Lin, Wei-Feng; Tang, Chuan-He

    2016-09-14

    The development of food-grade (nano)particles as a delivery system for poorly water soluble bioactives has recently attracted increasing attention. This work is an attempt to fabricate food protein-based nanoparticles as delivery systems for improving the water dispersion and bioaccessibility of phytosterols (PS) by an emulsification-evaporation method. The fabricated PS nanoparticles were characterized in terms of particle size, encapsulation efficiency (EE%) and loading amount (LA), and ξ-potential. Among all the test proteins, including soy protein isolate (SPI), whey protein concentrate (WPC) and sodium caseinate (SC), SC was confirmed to be the most suitable protein for the PS nano-formulation. Besides the type of protein, the particle size, EE% and LA of PS in the nanoparticles varied with the applied protein concentration in the aqueous phase and organic volume fraction. The freeze-dried PS nanoparticles with SC exhibited good water re-dispersion behavior and low crystallinity of PS. The LA of PS in the nanoparticles decreased upon storage, especially at high temperatures (e.g., >25 °C). The PS in the fabricated nanoparticles exhibited much better bioaccessibility than free PS. The findings would be of relevance for the fabrication of food-grade colloidal phytosterols, with great potential to be applied in functional food formulations.

  5. Comparative evaluation of the impact on endothelial cells induced by different nanoparticle structures and functionalization

    Directory of Open Access Journals (Sweden)

    Lisa Landgraf

    2015-01-01

    Full Text Available In the research field of nanoparticles, many studies demonstrated a high impact of the shape, size and surface charge, which is determined by the functionalization, of nanoparticles on cell viability and internalization into cells. This work focused on the comparison of three different nanoparticle types to give a better insight into general rules determining the biocompatibility of gold, Janus and semiconductor (quantum dot nanoparticles. Endothelial cells were subject of this study, since blood is the first barrier after intravenous nanoparticle application. In particular, stronger effects on the viability of endothelial cells were found for nanoparticles with an elongated shape in comparison to spherical ones. Furthermore, a positively charged nanoparticle surface (NH2, CyA leads to the strongest reduction in cell viability, whereas neutral and negatively charged nanoparticles are highly biocompatible to endothelial cells. These findings are attributed to a rapid internalization of the NH2-functionalized nanoparticles in combination with the damage of intracellular membranes. Interestingly, the endocytotic pathway seems to be a size-dependent process whereas nanoparticles with a size of 20 nm are internalized by caveolae-mediated endocytosis and nanoparticles with a size of 40 nm are taken up by clathrin-mediated internalization and macropinocytosis. Our results can be summarized to formulate five general rules, which are further specified in the text and which determine the biocompatibility of nanoparticles on endothelial cells. Our findings will help to design new nanoparticles with optimized properties concerning biocompatibility and uptake behavior with respect to the respective intended application.

  6. Langevin formulation of quantum dynamics

    International Nuclear Information System (INIS)

    Roncadelli, M.

    1989-03-01

    We first show that nonrelativistic quantum mechanics formulated at imaginary-(h/2 π) can formally be viewed as the Fokker-Planck description of a frictionless brownian motion, which occurs (in general) in an absorbing medium. We next offer a new formulation of quantum mechanics, which is basically the Langevin treatment of this brownian motion. Explicitly, we derive a noise-average representation for the transition probability W(X'',t''|X',t'), in terms of the solutions to a Langevin equation with a Gaussian white-noise. Upon analytic continuation back to real-(h/2 π),W(X'',t''|X',t') becomes the propagator of the original Schroedinger equation. Our approach allows for a straightforward application to quantum dynamical problems of the mathematical techniques of classical stochastic processes. Moreover, computer simulations of quantum mechanical systems can be carried out by using numerical programs based on the Langevin dynamics. (author). 19 refs, 1 tab

  7. Nanoparticle-based therapy for respiratory diseases

    Directory of Open Access Journals (Sweden)

    ADRIANA L. DA SILVA

    2013-03-01

    Full Text Available Nanotechnology is an emerging science with the potential to create new materials and strategies involving manipulation of matter at the nanometer scale (<100 nm. With size-dependent properties, nanoparticles have introduced a new paradigm in pharmacotherapy – the possibility of cell-targeted drug delivery with minimal systemic side effects and toxicity. The present review provides a summary of published findings, especially regarding to nanoparticle formulations for lung diseases. The available data have shown some benefits with nanoparticle-based therapy in the development of the disease and lung remodeling in respiratory diseases. However, there is a wide gap between the concepts of nanomedicine and the published experimental data and clinical reality. In addition, studies are still required to determine the potential of nanotherapy and the systemic toxicity of nanomaterials for future human use.

  8. Novel delivery system for natural products: Nano-curcumin formulations.

    Science.gov (United States)

    Rahimi, Hamid Reza; Nedaeinia, Reza; Sepehri Shamloo, Alireza; Nikdoust, Shima; Kazemi Oskuee, Reza

    2016-01-01

    Curcumin is extracted from Curcuma longa and regulates the intracellular signal pathways which control the growth of cancerous cell, inflammation, invasion and apoptosis. Curcumin molecules have special intrinsic features that can target the intracellular enzymes, genome (DNA) and messengers (RNA). A wide range of studies have been conducted on the physicochemical traits and pharmacological effects of curcumin on different diseases like cardiovascular diseases, diabetes, cancer, rheumatoid arthritis, Alzheimer's, inflammatory bowel disease (IBD), and even it has wound healing. Oral bioavailability of curcumin is rather poor, which would certainly put some boundaries in the employment of this drug. Bibliographical searches were performed using MEDLINE/ScienceDirect/OVID up to February 2015 using the following keywords (all fields): ("Curcumin" OR "Curcuma longa") AND [(nanoparticles) OR (Nanomicelles) OR (micro emulsions) OR (liposome) OR (phospholipid). Consequently, for any developments of curcumin in the future, analogues of curcumin that have better bioavailability or substitute formulations are needed crucially. These studies indicated that nanotechnology can formulate curcumin effectively, and this nano-formulated curcumin with a potent ability against various cancer cells, were represented to have better efficacy and bioavailability under in vivo conditions.

  9. Sustainable steric stabilization of colloidal titania nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Elbasuney, Sherif, E-mail: sherif_basuney2000@yahoo.com

    2017-07-01

    Graphical abstract: Controlled surface properties of titania nanoparticles via surface modification, flocculation from aqueous phase (a), stabilization in aqueous phase (b), extraction to organic phase (c). - Highlights: • Complete change in surface properties of titania nanoparticles from hydrophilic to hydrophobic. • Harvesting the formulated nanoparticles from the aqueous phase to the organic phase. • Exclusive surface modification in the reactor during nanoparticle synthesis. • Sustainable stabilization of titania nanoparticles in aqueous media with polar polymeric dispersant. - Abstract: A route to produce a stable colloidal suspension is essential if mono-dispersed particles are to be successfully synthesized, isolated, and used in subsequent nanocomposite manufacture. Dispersing nanoparticles in fluids was found to be an important approach for avoiding poor dispersion characteristics. However, there is still a great tendency for colloidal nanoparticles to flocculate over time. Steric stabilization can prevent coagulation by introducing a thick adsorbed organic layer which constitutes a significant steric barrier that can prevent the particle surfaces from coming into direct contact. One of the main features of hydrothermal synthesis technique is that it offers novel approaches for sustainable nanoparticle surface modification. This manuscript reports on the sustainable steric stabilization of titanium dioxide nanoparticles. Nanoparticle surface modification was performed via two main approaches including post-synthesis and in situ surface modification. The tuneable hydrothermal conditions (i.e. temperature, pressure, flow rates, and surfactant addition) were optimized to enable controlled steric stabilization in a continuous fashion. Effective post synthesis surface modification with organic ligand (dodecenyl succinic anhydride (DDSA)) was achieved; the optimum surface coating temperature was reported to be 180–240 °C to ensure DDSA ring opening

  10. Hydrophobically modified chitosan/gold nanoparticles for DNA delivery

    International Nuclear Information System (INIS)

    Bhattarai, Shanta Raj; Remant Bahadur, K.C.; Aryal, Santosh; Bhattarai, Narayan; Kim, Sun Young; Yi, Ho Keun; Hwang, Pyoung Han; Kim, Hak Yong

    2008-01-01

    Present study dealt an application of modified chitosan gold nanoparticles (Nac-6-Au) for the immobilization of necked plasmid DNA. Gold nanoparticles stabilized with N-acylated chitosan were prepared by graft-onto approach. The stabilized gold nanoparticles were characterized by different physico-chemical techniques such as UV-vis, TEM, ELS and DLS. MTT assay was used for in vitro cytotoxicity of the nanoparticles into three different cell lines (NIH 3T3, CT-26 and MCF-7). The formulation of plasmid DNA with the nanoparticles corresponds to the complex forming capacity and in-vitro/in-vivo transfection efficiency was studied via gel electrophoresis and transfection methods, respectively. Results showed the modified chitosan gold nanoparticles were well-dispersed and spherical in shape with average size around 10∼12 nm in triple distilled water at pH 7.4, and showed relatively no cytotoxicity at low concentration. Addition of plasmid DNA on the aqueous solution of the nanoparticles markedly reduced surface potential (50.0∼66.6%) as well as resulted in a 13.33% increase in hydrodynamic diameters of the formulated nanoparticles. Transfection efficiency of Nac-6-Au/DNA was dependent on cell type, and higher β-galactosidase activity was observed on MCF-7 breast cancer cell. Typically, this activity was 5 times higher in 4.5 mg/ml nanoparticles concentration than that achieved by the nanoparticles of other concentrations (and/or control). However, this activity was lower in in-vitro and dramatically higher in in-vivo than that of commercially available transfection kit (Lipofectin (registered) ) and DNA. From these results, it can be expected to develop alternative new vectors for gene delivery

  11. Hydrophobically modified chitosan/gold nanoparticles for DNA delivery

    Energy Technology Data Exchange (ETDEWEB)

    Bhattarai, Shanta Raj; Remant Bahadur, K.C.; Aryal, Santosh [Chonbuk National University, Department of Bionanosystem Engineering (Korea, Republic of); Bhattarai, Narayan [University of Washington, Department of Materials Science and Engineering (United States); Kim, Sun Young [Chonbuk National University, Department of Pediatrics, School of Medicine (Korea, Republic of); Yi, Ho Keun [Chonbuk National University, Department of Biochemistry, School of Dentisty (Korea, Republic of); Hwang, Pyoung Han [Chonbuk National University, Department of Pediatrics, School of Medicine (Korea, Republic of); Kim, Hak Yong [Chonbuk National University, Department of Textile Engineering (Korea, Republic of)], E-mail: khy@moak.chonbuk.ac.kr

    2008-01-15

    Present study dealt an application of modified chitosan gold nanoparticles (Nac-6-Au) for the immobilization of necked plasmid DNA. Gold nanoparticles stabilized with N-acylated chitosan were prepared by graft-onto approach. The stabilized gold nanoparticles were characterized by different physico-chemical techniques such as UV-vis, TEM, ELS and DLS. MTT assay was used for in vitro cytotoxicity of the nanoparticles into three different cell lines (NIH 3T3, CT-26 and MCF-7). The formulation of plasmid DNA with the nanoparticles corresponds to the complex forming capacity and in-vitro/in-vivo transfection efficiency was studied via gel electrophoresis and transfection methods, respectively. Results showed the modified chitosan gold nanoparticles were well-dispersed and spherical in shape with average size around 10{approx}12 nm in triple distilled water at pH 7.4, and showed relatively no cytotoxicity at low concentration. Addition of plasmid DNA on the aqueous solution of the nanoparticles markedly reduced surface potential (50.0{approx}66.6%) as well as resulted in a 13.33% increase in hydrodynamic diameters of the formulated nanoparticles. Transfection efficiency of Nac-6-Au/DNA was dependent on cell type, and higher {beta}-galactosidase activity was observed on MCF-7 breast cancer cell. Typically, this activity was 5 times higher in 4.5 mg/ml nanoparticles concentration than that achieved by the nanoparticles of other concentrations (and/or control). However, this activity was lower in in-vitro and dramatically higher in in-vivo than that of commercially available transfection kit (Lipofectin (registered) ) and DNA. From these results, it can be expected to develop alternative new vectors for gene delivery.

  12. Engineering of polymer-surfactant nanoparticles of doxycycline hydrochloride for ocular drug delivery.

    Science.gov (United States)

    Pokharkar, Varsha; Patil, Vikram; Mandpe, Leenata

    2015-01-01

    Physiologic barriers of the eye, short precorneal drug residence time and poor corneal penetration are the few reasons for reduced ocular bioavailability. This study was aimed to develop novel polymer-surfactant nanoparticles of hydrophilic drug doxycycline hydrochloride (DXY) to improve precorneal residence time and drug penetration. Nanoparticles were formulated using emulsion cross-linking method and the formulation was optimized using factorial design. The prepared formulation was characterized for particle size, ζ potential, encapsulation efficiency, in vitro drug release and ex vivo drug diffusion studies. The antibacterial activity studies were also carried out against Escherichia coli and Staphylococcus aureus using the cup-plate method. In vivo eye irritation study was carried out by a modified Draize test in rabbits. The particle size was found to be in the range of 331-850 nm. About 45-80% of the drug was found to be encapsulated in the nanoparticles. In vitro release demonstrated sustained release profile. Lower flux values in case of nanoparticles as compared to DXY pure drug solution in ex vivo diffusion studies confirmed the sustained release. The nanoparticles were found to be significantly effective (p nanoparticles in both the E. coli and S. aureus strains. The formulation was found to be stable over entire stability period. The developed formulation is safe and suitable for sustained ocular drug delivery.

  13. Nanoparticle shapes by using Wulff constructions and first-principles calculations

    Directory of Open Access Journals (Sweden)

    Georgios D. Barmparis

    2015-02-01

    Full Text Available Background: The majority of complex and advanced materials contain nanoparticles. The properties of these materials depend crucially on the size and shape of these nanoparticles. Wulff construction offers a simple method of predicting the equilibrium shape of nanoparticles given the surface energies of the material.Results: We review the mathematical formulation and the main applications of Wulff construction during the last two decades. We then focus to three recent extensions: active sites of metal nanoparticles for heterogeneous catalysis, ligand-protected nanoparticles generated as colloidal suspensions and nanoparticles of complex metal hydrides for hydrogen storage.Conclusion: Wulff construction, in particular when linked to first-principles calculations, is a powerful tool for the analysis and prediction of the shapes of nanoparticles and tailor the properties of shape-inducing species.

  14. The potential of PEGylated BaMnO3 nanoparticles as drug delivery agents

    International Nuclear Information System (INIS)

    Hayat, Khizar; Rafiq, M A; Hasan, M M; Khurshid, A; Ikram, M; Durrani, S K; Zaidi, S S Z

    2013-01-01

    Nanoparticles are extensively used as efficient drug carriers in various biological studies. PEGylated barium manganate powder consisting of nanoparticles was synthesized using a hydrothermal technique. The nanoparticle morphology of the powder was confirmed via scanning electron microscopy. The average diameter of the nanoparticles was ∼90 nm. The x-ray diffraction pattern revealed that these nanoparticles consisted of single phase polycrystalline 2H-BaMnO 3 . The PEGylated BaMnO 3 nanoparticles were loaded with 5-aminolevulinic acid (5-ALA) to evaluate their drug carrying potential. The toxicity of these nanoparticles was tested against the Hep2c cell line and found to be suitable for biological applications. It was seen that the drug uptake was a million times higher in the case of encapsulation compared to a conventional drug delivery system. This new formulation may find extensive use in nanomedicine as a multidrug delivery system. (letter)

  15. Dynamic light scattering and atomic force microscopy techniques for size determination of polyurethane nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Giehl Zanetti-Ramos, Betina [Laboratorio de Bioenergetica e Bioquimica de Macromoleculas, Departamento de Ciencias Farmaceuticas (Brazil)], E-mail: betinagzramos@pq.cnpq.br; Beddin Fritzen-Garcia, Mauricia [Laboratorio de Bioenergetica e Bioquimica de Macromoleculas, Departamento de Ciencias Farmaceuticas (Brazil); Schweitzer de Oliveira, Cristian; Avelino Pasa, Andre [Laboratorio de Filmes Finos e Superficie, Departamento de Fisica (Brazil); Soldi, Valdir [Grupo de Estudos em Materiais Polimericos, Departamento de Quimica, Universidade Federal de Santa Catarina, 88040-900, Florianopolis, SC (Brazil); Borsali, Redouane [Centre de Recherche sur les Macromolecules Vegetales CERMAV/CNRS, 38041 - Grenoble (France); Creczynski-Pasa, Tania Beatriz [Laboratorio de Bioenergetica e Bioquimica de Macromoleculas, Departamento de Ciencias Farmaceuticas (Brazil)

    2009-03-01

    Nanoparticles have applications in various industrial fields principally in drug delivery. Nowadays, there are several processes for manufacturing colloidal polymeric systems and methods of preparation as well as of characterization. In this work, Dynamic Light Scattering and Atomic Force Microscopy techniques were used to characterize polyurethane nanoparticles. The nanoparticles were prepared by miniemulsion technique. The lipophilic monomers, isophorone diisocyanate (IPDI) and natural triol, were emulsified in water containing surfactant. In some formulations the poly(ethylene glycol) was used as co-monomer to obtain the hydrophilic and pegylated nanoparticles. Polyurethane nanoparticles observed by atomic force microscopy (AFM) were spherical with diameter around 209 nm for nanoparticles prepared without PEG. From AFM imaging two populations of nanoparticles were observed in the formulation prepared with PEG (218 and 127 nm) while dynamic light scattering (DLS) measurements showed a monodisperse size distribution around 250 nm of diameters for both formulations. The polydispersity index of the formulations and the experimental procedures could influence the particle size determination with these techniques.

  16. Formulation and Characterization of Sustained Release Floating ...

    African Journals Online (AJOL)

    Purpose: To formulate sustained release gastroretentive microballoons of metformin hydrochloride with the objective of improving its bioavailability. Methods: Microballoons of metformin hydrochloride were formulated by solvent evaporation and diffusion method using varying mixtures of hydroxypropyl methylcellulose ...

  17. Perfume formulation: words and chats.

    Science.gov (United States)

    Ellena, Céline

    2008-06-01

    What does it mean to create fragrances with materials from chemistry and/or from nature? How are they used to display their characteristic differences, their own personality? Is it easier to create with synthetic raw materials or with essential oils? This review explains why a perfume formulation corresponds in fact to a conversation, an interplay between synthetic and natural perfumery materials. A synthetic raw material carries a single information, and usually is very linear. Its smell is uniform, clear, and faithful. Natural raw materials, on the contrary, provide a strong, complex and generous image. While a synthetic material can be seen as a single word, a natural one such as rose oil could be compared to chatting: cold, warm, sticky, heavy, transparent, pepper, green, metallic, smooth, watery, fruity... full of information. Yet, if a very small amount of the natural material is used, nothing happens, the fragrance will not change. However, if a large amount is used, the rose oil will swallow up everything else. The fragrance will smell of nothing else except rose! To formulate a perfume is not to create a culinary recipe, with only dosing the ingredients in well-balanced amounts. To formulate rather means to flexibly knit materials together with a lively stitch, meeting or repelling each other, building a pleasant form, which is neither fixed, nor solid, nor rigid. A fragrance has an overall structure, which ranges from a clear sound, made up of stable, unique, and linear items, to a background chat, comfortable and reassuring. But that does, of course, not mean that there is only one way of creating a fragrance!

  18. Formulation of soy oil products

    Directory of Open Access Journals (Sweden)

    Woerfel, John B.

    1995-12-01

    Full Text Available The paper comments different formulations of soy oil products such as salad and cooking oils, margarine, shortenings, commercial shortenings, frying shortenings, and fluid shortenings. Hydrogenation and its influence on final products is also included.

    El trabajo presenta diferentes formulaciones a base de aceite de soja tales como aceites para ensalada y cocinado, margarina, grasas sólidas (shortenings, grasas sólidas comerciales, grasas sólidas para frituras y grasas fluidas. Hace también referencia al proceso de hidrogenación y a sus efectos en los productos finales.

  19. Protein nanoparticle: A unique system as drug delivery vehicles

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... Nanobiotechnology Research Center, Faculty of Chemical Engineering, Babol University of Technology, Iran. Accepted 8 December, 2008 .... found as the major component of skin, bones and connective tissue (Coester et al., .... It is always a challenge to formulate nanoparticles with the smallest size ...

  20. Development and Optimization of Insulin-Chitosan Nanoparticles ...

    African Journals Online (AJOL)

    Purpose: To optimize the preparation of insulin-chitosan nanoparticles (ICNS) using response surface methodology (RSM). Methods: ICNS were formulated through ionic cross linking method. The effects of the ratio between insulin and chitosan, pH of the medium and rotation speed on insulin encapsulation efficiency (EE) ...

  1. Facts and evidences on the lyophilization of polymeric nanoparticles for drug delivery.

    Science.gov (United States)

    Fonte, Pedro; Reis, Salette; Sarmento, Bruno

    2016-03-10

    Lyophilization has been used to improve the long-term stability of polymeric nanoparticles for drug delivery applications, avoiding their instability in suspension. However, this dehydration process may induce stresses to nanoparticles, mitigated by the use of some excipients such as cryo- and lyoprotectants. Still, the lyophilization of polymeric nanoparticles is frequently based in empirical principles, without considering the physical-chemical properties of formulations and the engineering principles of lyophilization. Therefore, the optimization of formulations and the lyophilization cycle is crucial to obtain a good lyophilizate, and guarantee the preservation of nanoparticle stability. The proper characterization of the lyophilizate and nanoparticles has a great importance in achieving these purposes. This review updates the fundaments involved in the optimization procedures for lyophilization of polymeric nanoparticles, with the aim of obtaining the maximum stability of formulations. Different characterization methods to obtain and guarantee a good lyophilized product are also discussed. A special focus is given to encapsulated therapeutic proteins. Overall, this review is a contribution for the understanding of the parameters involved in the lyophilization of polymeric nanoparticles. This may definitely help future works to obtain lyophilized nanoparticles with good quality and with improved therapeutic benefits. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Formulation, Preparation, and Characterization of Polyurethane Foams

    Science.gov (United States)

    Pinto, Moises L.

    2010-01-01

    Preparation of laboratory-scale polyurethane foams is described with formulations that are easy to implement in experiments for undergraduate students. Particular attention is given to formulation aspects that are based on the main chemical reactions occurring in polyurethane production. This allows students to develop alternative formulations to…

  3. Performance Evaluation of Abrasive Grinding Wheel Formulated ...

    African Journals Online (AJOL)

    This paper presents a study on the formulation and manufacture of abrasive grinding wheel using locally formulated silicon carbide abrasive grains. Six local raw material substitutes were identified through pilot study and with the initial mix of the identified materials, a systematic search for an optimal formulation of silicon ...

  4. Using a modified shepards method for optimization of a nanoparticulate cyclosporine a formulation prepared by a static mixer technique.

    Science.gov (United States)

    Douroumis, Dionysios; Scheler, Stefan; Fahr, Alfred

    2008-02-01

    An innovative methodology has been used for the formulation development of Cyclosporine A (CyA) nanoparticles. In the present study the static mixer technique, which is a novel method for producing nanoparticles, was employed. The formulation optimum was calculated by the modified Shepard's method (MSM), an advanced data analysis technique not adopted so far in pharmaceutical applications. Controlled precipitation was achieved injecting the organic CyA solution rapidly into an aqueous protective solution by means of a static mixer. Furthermore the computer based MSM was implemented for data analysis, visualization, and application development. For the optimization studies, the gelatin/lipoid S75 amounts and the organic/aqueous phase were selected as independent variables while the obtained particle size as a dependent variable. The optimum predicted formulation was characterized by cryo-TEM microscopy, particle size measurements, stability, and in vitro release. The produced nanoparticles contain drug in amorphous state and decreased amounts of stabilizing agents. The dissolution rate of the lyophilized powder was significantly enhanced in the first 2 h. MSM was proved capable to interpret in detail and to predict with high accuracy the optimum formulation. The mixer technique was proved capable to develop CyA nanoparticulate formulations.

  5. Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: Challenges, considerations and strategy.

    Science.gov (United States)

    Dobrovolskaia, Marina A

    2015-12-28

    Assorted challenges in physicochemical characterization, sterilization, depyrogenation, and in the assessment of pharmacology, safety, and efficacy profiles accompany pre-clinical development of nanotechnology-formulated drugs. Some of these challenges are not unique to nanotechnology and are common in the development of other pharmaceutical products. However, nanoparticle-formulated drugs are biochemically sophisticated, which causes their translation into the clinic to be particularly complex. An understanding of both the immune compatibility of nanoformulations and their effects on hematological parameters is now recognized as an important step in the (pre)clinical development of nanomedicines. An evaluation of nanoparticle immunotoxicity is usually performed as a part of a traditional toxicological assessment; however, it often requires additional in vitro and in vivo specialized immuno- and hematotoxicity tests. Herein, I review literature examples and share the experience with the NCI Nanotechnology Characterization Laboratory assay cascade used in the early (discovery-level) phase of pre-clinical development to summarize common challenges in the immunotoxicological assessment of nanomaterials, highlight considerations and discuss solutions to overcome problems that commonly slow or halt the translation of nanoparticle-formulated drugs toward clinical trials. Special attention will be paid to the grand-challenge related to detection, quantification and removal of endotoxin from nanoformulations, and practical considerations related to this challenge. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Parenteral formulation of an antileishmanial drug candidate--tackling poor solubility, chemical instability, and polymorphism.

    Science.gov (United States)

    Kupetz, Eva; Preu, Lutz; Kunick, Conrad; Bunjes, Heike

    2013-11-01

    The paullon chalcone derivative KuRei300 is active against Leishmania donovani, the protozoans causing visceral leishmaniasis. The aim of this study was the development of a parenteral formulation of the virtually water insoluble compound in order to enable future studies in mice. Mixed lecithin/bile salt micelles, liposomes, supercooled smectic cholesterol myristate nanoparticles, cubic phase nanoparticles and a triglyceride emulsion were screened for their solubilizing properties. Due to the limited available amount of KuRei300 a passive loading approach with pre-formulated carriers that were incubated with drug substance deposited onto the walls of glass vials was used. The loading capacities of the nanocarriers, the influence of the solid state properties of the drug and its deposits on the loading results and chemical stability aspects of KuRei300 were investigated. Employed methods included HPLC, UV spectroscopy, (1)H NMR, XRPD, and DSC. All nanocarriers substantially improved the solubility of KuRei300; the mixed micelles exhibited the highest drug load. Related to the lipid matrix, however, the smectic nanoparticles solubilized the significantly highest amount of drug. Loading from physically altered drug deposits improved the obtainable concentration to the threefold compared with untreated drug powder. Formulations with KuRei300 must be stored excluded from light under a nitrogen atmosphere as the substance is susceptible to photoisomerization and decomposition. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Formulation and Optimization of Eudragit RS PO-Tenofovir Nanocarriers Using Box-Behnken Experimental Design

    Directory of Open Access Journals (Sweden)

    Kefilwe Matlhola

    2015-01-01

    Full Text Available The objective of present study was to develop an optimized polymeric nanoparticle system for the antiretroviral drug tenofovir. A modified nanoprecipitation method was used to prepare Eudragit RS PO nanoparticles of the drug. The effect of amount of polymer, surfactant concentration, and sonication time on particle size, particle distribution, encapsulation efficiency (EE, and zeta potential were assessed and optimized utilizing a three-factor, three-level Box-Behnken Design (BBD of experiment. Fifteen formulations of nanoparticles were prepared as per BBD and evaluated for particle size, polydispersity index (PDI, EE, and zeta potential. The results showed that the measured mean particle sizes were in the range of 233 to 499 nm, PDI ranged from 0.094 to 0.153, average zeta potential ranged from −19.9 to −45.8 mV, and EE ranged between 98 and 99%. The optimized formulation was characterized for in vitro drug release and structural characterization. The mean particle size of this formulation was 233 nm with a PDI of 0.0107. It had a high EE of 98% and average zeta potential of −35 mV, an indication of particle stability. The FTIR showed some noncovalent interactions between the drug and polymer but a sustained release was observed in vitro for up to 80 hours.

  8. In vitro effect of imatinib mesylate loaded on polybutylcyanoacrylate nanoparticles on leukemia cell line K562.

    Science.gov (United States)

    Hasandoost, Leyla; Akbarzadeh, Azim; Attar, Hossein; Heydarinasab, Amir

    2017-05-01

    The study aimed to prepare imatinib mesylate-loaded polybutylcyanoacrylate (PBCA) nanoparticles and evaluate their efficacy on leukemia cell line K562. The formulation was prepared by miniemulsion polymerization technique. Nanoparticles were characterized by dynamic light scattering (DLS), spectrophotometry, Fourier transform infrared spectroscopy (FTIR), dialysis membrane, and 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) techniques. Nanoscale particles with high encapsulation efficiency (86%) and physical entrapment of drug were observed. In addition, nanoparticles showed suitable drug retention capability and potentiate the cytotoxicity effects of imatinib mesylate. Findings of study suggested PBCA nanoparticles are promising carrier for imatinib mesylate delivery to leukemia cell line K562.

  9. Radiosensitizing Silica Nanoparticles Encapsulating Docetaxel for Treatment of Prostate Cancer.

    Science.gov (United States)

    Belz, Jodi; Castilla-Ojo, Noelle; Sridhar, Srinivas; Kumar, Rajiv

    2017-01-01

    The applications of nanoparticles in oncology include enhanced drug delivery, efficient tumor targeting, treatment monitoring, and diagnostics. The "theranostic properties" associated with nanoparticles have shown enhanced delivery of chemotherapeutic drugs with superior imaging capabilities and minimal toxicities. In conventional chemotherapy, only a fraction of the administered drug reaches the tumor site or cancer cells. For successful translation of these formulations, it is imperative to evaluate the design and properties of these nanoparticles. Here, we describe the design of ultra-small silica nanoparticles to encapsulate a radiosensitizing drug for combined chemoradiation therapy. The small size of nanoparticles allows for better dispersion and uptake of the drug within the highly vascularized tumor tissue. Silica nanoparticles are synthesized using an oil-in-water microemulsion method. The microemulsion method provides a robust synthetic route in which the inner hydrophobic core is used to encapsulate chemotherapy drug, docetaxel while the outer hydrophilic region provides dispersibility of the synthesized nanoparticles in an aqueous environment. Docetaxel is commonly used for treatment of resistant or metastatic prostate cancer, and is known to have radiosensitizing properties. Here, we describe a systematic approach for synthesizing these theranostic nanoparticles for application in prostate cancer.

  10. Lipid Self-Assemblies and Nanostructured Emulsions for Cosmetic Formulations

    Directory of Open Access Journals (Sweden)

    Chandrashekhar V. Kulkarni

    2016-10-01

    Full Text Available A majority of cosmetic products that we encounter on daily basis contain lipid constituents in solubilized or insolubilized forms. Due to their amphiphilic nature, the lipid molecules spontaneously self-assemble into a remarkable range of nanostructures when mixed with water. This review illustrates the formation and finely tunable properties of self-assembled lipid nanostructures and their hierarchically organized derivatives, as well as their relevance to the development of cosmetic formulations. These lipid systems can be modulated into various physical forms suitable for topical administration including fluids, gels, creams, pastes and dehydrated films. Moreover, they are capable of encapsulating hydrophilic, hydrophobic as well as amphiphilic active ingredients owing to their special morphological characters. Nano-hybrid materials with more elegant properties can be designed by combining nanostructured lipid systems with other nanomaterials including a hydrogelator, silica nanoparticles, clays and carbon nanomaterials. The smart materials reviewed here may well be the future of innovative cosmetic applications.

  11. Pure drug nanoparticles in tablets: what are the dissolution limitations?

    International Nuclear Information System (INIS)

    Heng, Desmond; Ogawa, Keiko; Cutler, David J.; Chan, Hak-Kim; Raper, Judy A.; Ye Lin; Yun, Jimmy

    2010-01-01

    There has been increasing interests for drug companies to incorporate drug nanoparticles into their existing formulations. However, technical knowledge in this area is still in its infancy and more study needs to be done to stimulate growth in this fledging field. There is a need to scrutinize the performance of pure drug nanoparticles in tablets, particularly relating formulation variables to their dissolution performance. Application of the pure form, synthesized without the use of surfactants or stabilizers, is often preferred to maximize drug loading and also to minimize toxicity. Cefuroxime axetil, a poorly water-soluble cephalosporin antibiotic, was used as the model drug in the formulation development. Drug release rate, tablet disintegration time, tensile strength and energy of failure were predominantly influenced by the amount of super-disintegrant, amount of surfactant, compression force and diluent species, respectively. The compression rate had minimal impact on the responses. The main hurdle confronting the effective use of pure drug nanoparticles in tablets is the difficulty in controlling aggregation in solution, which could potentially be aggravated by the tabletting process. Through the use of elevated levels of surfactants (8 w/w% sodium dodecyl sulphate), drug release from the nanoparticle preparation was enhanced from 58.0 ± 2.7% to 72.3 ± 0.7% in 10 min. Hence, it is recommended that physical formulations for pure drug nanoparticles be focused on the particle de-aggregation step in solution, if much higher rates are to be desired. In conclusion, even though pure drug nanoparticles could be easily synthesized, limitations from aggregation may need to be overcome, before successful application in tablets can be fully realized.

  12. Pure drug nanoparticles in tablets: what are the dissolution limitations?

    Energy Technology Data Exchange (ETDEWEB)

    Heng, Desmond [Institute of Chemical and Engineering Sciences (Singapore); Ogawa, Keiko [Nitto Denko Co. Ltd., Medical Division (Japan); Cutler, David J.; Chan, Hak-Kim, E-mail: kimc@pharm.usyd.edu.a [University of Sydney, Advanced Drug Delivery Group, Faculty of Pharmacy, A15 (Australia); Raper, Judy A. [University of Wollongong, Vice Chancellor' s Unit (Australia); Ye Lin [University of Sydney, School of Aerospace, Mechanical and Mechatronic Engineering (Australia); Yun, Jimmy [Nanomaterials Technology Pty. Ltd. (Singapore)

    2010-06-15

    There has been increasing interests for drug companies to incorporate drug nanoparticles into their existing formulations. However, technical knowledge in this area is still in its infancy and more study needs to be done to stimulate growth in this fledging field. There is a need to scrutinize the performance of pure drug nanoparticles in tablets, particularly relating formulation variables to their dissolution performance. Application of the pure form, synthesized without the use of surfactants or stabilizers, is often preferred to maximize drug loading and also to minimize toxicity. Cefuroxime axetil, a poorly water-soluble cephalosporin antibiotic, was used as the model drug in the formulation development. Drug release rate, tablet disintegration time, tensile strength and energy of failure were predominantly influenced by the amount of super-disintegrant, amount of surfactant, compression force and diluent species, respectively. The compression rate had minimal impact on the responses. The main hurdle confronting the effective use of pure drug nanoparticles in tablets is the difficulty in controlling aggregation in solution, which could potentially be aggravated by the tabletting process. Through the use of elevated levels of surfactants (8 w/w% sodium dodecyl sulphate), drug release from the nanoparticle preparation was enhanced from 58.0 {+-} 2.7% to 72.3 {+-} 0.7% in 10 min. Hence, it is recommended that physical formulations for pure drug nanoparticles be focused on the particle de-aggregation step in solution, if much higher rates are to be desired. In conclusion, even though pure drug nanoparticles could be easily synthesized, limitations from aggregation may need to be overcome, before successful application in tablets can be fully realized.

  13. Pure drug nanoparticles in tablets: what are the dissolution limitations?

    Science.gov (United States)

    Heng, Desmond; Ogawa, Keiko; Cutler, David J.; Chan, Hak-Kim; Raper, Judy A.; Ye, Lin; Yun, Jimmy

    2010-06-01

    There has been increasing interests for drug companies to incorporate drug nanoparticles into their existing formulations. However, technical knowledge in this area is still in its infancy and more study needs to be done to stimulate growth in this fledging field. There is a need to scrutinize the performance of pure drug nanoparticles in tablets, particularly relating formulation variables to their dissolution performance. Application of the pure form, synthesized without the use of surfactants or stabilizers, is often preferred to maximize drug loading and also to minimize toxicity. Cefuroxime axetil, a poorly water-soluble cephalosporin antibiotic, was used as the model drug in the formulation development. Drug release rate, tablet disintegration time, tensile strength and energy of failure were predominantly influenced by the amount of super-disintegrant, amount of surfactant, compression force and diluent species, respectively. The compression rate had minimal impact on the responses. The main hurdle confronting the effective use of pure drug nanoparticles in tablets is the difficulty in controlling aggregation in solution, which could potentially be aggravated by the tabletting process. Through the use of elevated levels of surfactants (8 w/w% sodium dodecyl sulphate), drug release from the nanoparticle preparation was enhanced from 58.0 ± 2.7% to 72.3 ± 0.7% in 10 min. Hence, it is recommended that physical formulations for pure drug nanoparticles be focused on the particle de-aggregation step in solution, if much higher rates are to be desired. In conclusion, even though pure drug nanoparticles could be easily synthesized, limitations from aggregation may need to be overcome, before successful application in tablets can be fully realized.

  14. Gemcitabine hydrochloride-loaded liposomes and nanoparticles: comparison of encapsulation efficiency, drug release, particle size, and cytotoxicity.

    Science.gov (United States)

    Yalcin, Tahir Emre; Ilbasmis-Tamer, Sibel; Ibisoglu, Burçin; Özdemir, Aysun; Ark, Mustafa; Takka, Sevgi

    2018-01-01

    The aim of this study is to formulate and compare the physicochemical properties of negatively charged liposomes and poly(lactide-co-glycolide) (PLGA) nanoparticles loaded with gemcitabine hydrochloride. The influence of the formulation variables on the liposome and nanoparticle properties on particle size, zeta potential, encapsulation efficiency, and drug release was evaluated. Although the PEGylated nanoparticles and PEGylated liposomes were of the same size (∼200 nm), the encapsulation efficiency was 1.4 times higher for PEGylated liposomes than for PEGylated nanoparticles. The optimized formulation of PEGylated liposomes and PEGylated nanoparticles had 26.1 ± 0.18 and 18.8 ± 1.52% encapsulation efficiency, respectively. The release of drug from the PEGylated liposomes and PEGylated nanoparticles exhibited a biphasic pattern that was characterized by a fast initial release during the first 2 h followed by a slower continuous release. Transmission electron microscopy (TEM) images identified separate circular structures of the liposomes and nanoparticles. The in vitro cytotoxicity of the optimized formulations was assessed in MCF-7 and MDA-MB-231 cells, and the results showed that the cytotoxicity effect of the gemcitabine hydrochloride-loaded liposomes and nanoparticles was more than commercial product Gemko ® and gemcitabine hydrochloride solution.

  15. Anionic solid lipid nanoparticles supported on protamine/DNA complexes

    International Nuclear Information System (INIS)

    Ye Jiesheng; Liu Chunxi; Chen Zhijin; Zhang Na; Wang Aihua

    2008-01-01

    The objective of this study was to design novel anionic ternary nanoparticles for gene delivery. These ternary nanoparticles were equipped with protamine/DNA binary complexes (150-200 nm) as the support, and the anionic formation was achieved by absorption of anionic solid lipid nanoparticles (≤20 nm) onto the surface of the binary complexes. The small solid lipid nanoparticles (SLNs) were prepared by a modified film dispersion-ultrasonication method, and adsorption of the anionic SLNs onto the binary complexes was typically carried out in water via electrostatic interaction. The formulated ternary nanoparticles were found to be relatively uniform in size (257.7 ± 10.6 nm) with a 'bumpy' surface, and the surface charge inversion from 19.28 ± 1.14 mV to -17.16 ± 1.92 mV could be considered as evidence of the formation of the ternary nanoparticles. The fluorescence intensity measurements from three batches of the ternary nanoparticles gave a mean adsorption efficiency of 96.75 ± 1.13%. Circular dichroism spectra analysis showed that the protamine/DNA complexes had been coated by small SLNs, and that the anionic ternary nanoparticles formed did not disturb the construction of the binary complexes. SYBR Green I analysis suggested that the ternary nanoparticles could protect the DNA from nuclease degradation, and cell viability assay results showed that they exhibit lower cytotoxicity to A549 cells compared with the binary complexes and lipofectamine. The transfection efficiency of the ternary nanoparticles was better than that of naked DNA and the binary complexes, and almost equal to that of lipofectamine/DNA complexes, as revealed by inversion fluorescence microscope observation. These results indicated that the anionic ternary nanoparticles could facilitate gene transfer in cultured cells, and might alleviate the drawbacks of the conventional cationic vector/DNA complexes for gene delivery in vivo

  16. Block copolymer self-assembly fundamentals and applications in formulation of nano-structured fluids

    Science.gov (United States)

    Sarkar, Biswajit

    Dispersions of nanoparticles in polymer matrices form hybrid materials that can exhibit superior structural and functional properties and find applications in e.g. thermo-plastics, electronics, polymer electrolytes, catalysis, paint formulations, and drug delivery. Control over the particle location and orientation in the polymeric matrices are essential in order to realize the enhanced mechanical, electrical, and optical properties of the nanohybrids. Block copolymers, composed of two or more different monomers, are promising for controlling particle location and orientation because of their ability to organize into ordered nanostructures. Fundamental questions pertaining to nanoparticle-polymer interfacial interactions remain open and formulate the objectives of our investigation. Particle-polymer enthalpic and entropic interactions control the nanoparticle dispersion in polymer matrices. Synthetic chemical methods for modifying the particle surface in order to control polymer-particle interactions are involved and large scale production is not possible. In the current approach, a physical method is employed to control polymer-particle interactions. The use of commercially available solvents is found to be effective in modifying particle-polymer interfacial interactions. The approach is applicable to a wide range of particle-polymer systems and can thereby enable large scale processing of polymer nanohybrids. The systems of silica nanoparticles dispersed in long-range or short-range self-assembled structures of aqueous poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers (Pluronics) is considered here. The effect of various parameters such as the presence of organic solvents, pH, and particle size on the block copolymer organization and the ensuing particle-polymer interactions are investigated. Favorable surface interactions between the deprotonated silica nanoparticle and PEO-rich domain facilitate particle

  17. Nanoparticle-nanoparticle interactions in biological media by Atomic Force Microscopy

    Science.gov (United States)

    Pyrgiotakis, Georgios; Blattmann, Christoph O.; Pratsinis, Sotiris; Demokritou, Philip

    2015-01-01

    Particle-particle interactions in physiological media are important determinants for nanoparticle fate and transport. Herein, such interactions are assessed by a novel Atomic Force Microscopy (AFM) based platform. Industry-relevant CeO2, Fe2O3, and SiO2 nanoparticles of various diameters were made by the flame spray pyrolysis (FSP) based Harvard Versatile Engineering Nanomaterials Generation System (Harvard VENGES). The nanoparticles were fully characterized structurally and morphologically and their properties in water and biological media were also assessed. The nanoparticles were attached on AFM tips and deposited on Si substrates to measure particle–particle interactions. The corresponding force was measured in air, water and biological media that are widely used in toxicological studies. The presented AFM based approach can be used to assess the agglomeration potential of nanoparticles in physiological fluids. The agglomeration potential of CeO2 nanoparticles in water and RPMI 1640 (Roswell Park Memorial Institute formulation 1640) was inversely proportional to their primary particle (PP) diameter, but for Fe2O3 nanoparticles, that potential is independent of PP diameter in these media. Moreover, in RPMI+10% Fetal Bovine Serum (FBS) the corona thickness and dispersibility of the CeO2 is independent of PP diameter while for Fe2O3, the corona thickness and dispersibility were inversely proportional to PP diameter. The present method can be combined with (dynamic light scattering (DLS), proteomics, and computer simulations to understand the nano-bio interactions, with emphasis on the agglomeration potential of nanoparticles and their transport in physiological media. PMID:23978039

  18. Evaluation of Antibacterial Properties of Dental Adhesives Containing Metal Nanoparticles

    Directory of Open Access Journals (Sweden)

    Shafiei F

    2018-03-01

    Full Text Available Statement of problem: Secondary dental caries is a common clinical finding in composite restoration. The development of a bactericidal dental adhesive provides a promising method to reduce the risk of secondary caries. Objectives: This study aimed to assess the antibacterial activity of silver (Ag and titanium dioxide (TiO2 nanoparticles incorporated into an experimental dentin bonding agent formulation. Materials and Methods: Ag and TiO2 nanoparticles at 0.05, 0.1, 0.2, 0.5, and 1 wt% concentrations were incorporated into the adhesives. The suspensions were sonicated to ensure homogenous dispersion of nanoparticles in the adhesive system. Formulation was composed of acetone, 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxyphenyl]propane (Bis-GMA, 1,6-bis-[2-methacryloyloxyethyl carbonyl amino]-2,4,4-trimethylhexane (UDMA, trimethylolpropane trimethacrylate (TMPTMA, 2-hydroxyethyl methacrylate (HEMA, and photoinitiator, with polyvinylpyrrolidone (PVP as the stabilizer. We counted the colony-forming units (CFU% of two cariogenic bacteria, Streptococcus mutans (S. mutans and Lactobacillus acidophilus (L. acidophilus, that were exposed to the powdered light cured adhesive specimens. The effects of various concentrations of each nanoparticle were compared by one-way ANOVA, followed by the post hoc Bonferroni test. Results: All samples exhibited definite antibacterial activity (P<0.05 compared to the control specimens. The Ag nanoparticle samples showed higher antibacterial properties compared to the TiO2 nanoparticle samples. Increasing the concentration of nanoparticles resulted in significant differences in bactericidal properties, with the exception of 0.2 to 0.5 wt% Ag nanoparticle specimens exposed to S. mutans and the 0.2 to 0.5 wt% TiO2 nanoparticle specimens exposed to L. acidophilus. Conclusions: These metal-based nanoparticles exhibited dose-dependent bactericidal activities. The Ag nanoparticles had higher antibacterial activity compared to the

  19. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

    Science.gov (United States)

    Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

    2016-03-01

    Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

  20. Preparation and characterization of spray-dried tobramycin powders containing nanoparticles for pulmonary delivery.

    Science.gov (United States)

    Pilcer, Gabrielle; Vanderbist, Francis; Amighi, Karim

    2009-01-05

    Using high-pressure homogenization and spray-drying techniques, novel formulations were developed for manufacturing dry powder for inhalation, composed of a mixture of micro- and nanoparticles in order to enhance lung deposition. Particle size analysis was performed by laser diffraction. Spray-drying was applied in order to retrieve nanoparticles in dried-powder state from tobramycin nanosuspensions. The aerolization properties of the different formulations were evaluated by a multi-stage liquid impinger. Suspensions of nanoparticles of tobramycin containing Na glycocholate at 2% (w/w) relative to tobramycin content and presenting a mean particle size about 200 nm were produced. The results from the spray-dried powders showed that the presence of nanoparticles in the formulations improved particle dispersion properties during inhalation. The fine particle fraction (percentage of particles below 5 microm) increased from 36% for the raw micronized tobramycin material to about 61% for the most effective formulation. These new nanoparticle-containing tobramycin DPI formulations, based on the use of very low level of excipient and presenting high lung deposition properties, offer very important perspectives for improving the delivery of drugs to the pulmonary tract.

  1. Non-carrier nanoparticles adjuvant modular protein vaccine in a particle-dependent manner.

    Directory of Open Access Journals (Sweden)

    Arjun Seth

    Full Text Available Nanoparticles are increasingly used to adjuvant vaccine formulations due to their biocompatibility, ease of manufacture and the opportunity to tailor their size, shape, and physicochemical properties. The efficacy of similarly-sized silica (Si-OH, poly (D,L-lactic-co-glycolic acid (PLGA and poly caprolactone (PCL nanoparticles (nps to adjuvant recombinant capsomere presenting antigenic M2e modular peptide from Influenza A virus (CapM2e was investigated in vivo. Formulation of CapM2e with Si-OH or PLGA nps significantly boosted the immunogenicity of modular capsomeres, even though CapM2e was not actively attached to the nanoparticles prior to injection (i.e., formulation was by simple mixing. In contrast, PCL nps showed no significant adjuvant effect using this simple-mixing approach. The immune response induced by CapM2e alone or formulated with nps was antibody-biased with very high antigen-specific antibody titer and less than 20 cells per million splenocytes secreting interferon gamma. Modification of silica nanoparticle surface properties through amine functionalization and pegylation did not lead to significant changes in immune response. This study confirms that simple mixing-based formulation can lead to effective adjuvanting of antigenic protein, though with antibody titer dependent on nanoparticle physicochemical properties.

  2. Formulation and Characterization of Antibacterial Fluoride-releasing Sealants

    Science.gov (United States)

    Fan, Yuwei; Townsend, Janice; Wang, Yapin; Lee, Eun Chee; Evans, Katie; Hender, Erica; Hagan, Joseph L.; Xu, Xiaoming

    2013-01-01

    Purpose The purpose of this study was to formulate and characterize experimental antibacterial fluoride-releasing sealants and compare them with commercial sealants for fluoride release, recharge, adhesion, and microleakage. Methods Two experimental sealants (Exp-1, Exp-2) containing a synthesized antibacterial fluoride-releasing monomer and fluoride-releasing filler were formulated. Exp-2 also contained NovaMin nanoparticles. Commercial sealants Clinpro (CL) FluoroShield (FS), and SeLECT Defense (E34) were also included. Fluoride release from disk samples in deionized water was measured daily using an ion-selective electrode for 14 days, and after recharging with Neutra-Foam (2.0% sodium fluoride), fluoride was measured for 5 days. Microtensile bonding strengths (MTBS) to enamel were tested after 24-hour storage in water at 37°C or thermocycling 5-55°C for 1,000 cycles. A microleakage test was conducted on extracted teeth using a dye-penetration method. The data were analyzed using analysis of variance with the Tukey’s honestly significant difference test and Kruskal-Wallis test. Results Exp-1 and Exp-2 had significantly higher fluoride release and recharge capabilities than CL and FL (P<.05). All tested sealants had similar MTBS before and after thermocycling. Exp-2 and Exp-1 had significantly lower microleakage scores (P<.05) than other groups. Conclusion The experimental sealants had higher fluoride release and recharge capabilities and similar or better retention than commercial sealants. PMID:23635887

  3. Nanosized rods agglomerates as a new approach for formulation of a dry powder inhaler.

    Science.gov (United States)

    Salem, Hf; Abdelrahim, Me; Eid, K Abo; Sharaf, Ma

    2011-01-01

    Nanosized dry powder inhalers provide higher stability for poorly water-soluble drugs as compared with liquid formulations. However, the respirable particles must have a diameter of 1-5 μm in order to deposit in the lungs. Controlled agglomeration of the nanoparticles increases their geometric particle size so they can deposit easily in the lungs. In the lungs, they fall apart to reform nanoparticles, thus enhancing the dissolution rate of the drugs. Theophylline is a bronchodilator with poor solubility in water. Nanosized theophylline colloids were formed using an amphiphilic surfactant and destabilized using dilute sodium chloride solutions to form the agglomerates. The theophylline nanoparticles thus obtained had an average particle size of 290 nm and a zeta potential of -39.5 mV, whereas the agglomerates were 2.47 μm in size with a zeta potential of -28.9 mV. The release profile was found to follow first-order kinetics (r(2) > 0.96). The aerodynamic characteristics of the agglomerated nanoparticles were determined using a cascade impactor. The behavior of the agglomerate was significantly better than unprocessed raw theophylline powder. In addition, the nanoparticles and agglomerates resulted in a significant improvement in the dissolution of theophylline. The results obtained lend support to the hypothesis that controlled agglomeration strategies provide an efficient approach for the delivery of poorly water-soluble drugs into the lungs.

  4. Formulation, stabilisation and encapsulation of bacteriophage for phage therapy.

    Science.gov (United States)

    Malik, Danish J; Sokolov, Ilya J; Vinner, Gurinder K; Mancuso, Francesco; Cinquerrui, Salvatore; Vladisavljevic, Goran T; Clokie, Martha R J; Garton, Natalie J; Stapley, Andrew G F; Kirpichnikova, Anna

    2017-11-01

    for formulation and encapsulation is shelf life and storage of phage to ensure reproducible dosages. Other drivers include formulation of phage for encapsulation in micro- and nanoparticles for effective delivery, encapsulation in stimuli responsive systems for triggered controlled or sustained release at the targeted site of infection. Encapsulation of phage (e.g. in liposomes) may also be used to increase the circulation time of phage for treating systemic infections, for prophylactic treatment or to treat intracellular infections. We then proceed to document approaches used in the published literature on the formulation and stabilisation of phage for storage and encapsulation of bacteriophage in micro- and nanostructured materials using freeze drying (lyophilization), spray drying, in emulsions e.g. ointments, polymeric microparticles, nanoparticles and liposomes. As phage therapy moves forward towards Phase III clinical trials, the review concludes by looking at promising new approaches for micro- and nanoencapsulation of phages and how these may address gaps in the field. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  5. A New Method for Evaluating Actual Drug Release Kinetics of Nanoparticles inside Dialysis Devices via Numerical Deconvolution.

    Science.gov (United States)

    Zhou, Yousheng; He, Chunsheng; Chen, Kuan; Ni, Jieren; Cai, Yu; Guo, Xiaodi; Wu, Xiao Yu

    2016-12-10

    Nanoparticle formulations have found increasing applications in modern therapies. To achieve desired treatment efficacy and safety profiles, drug release kinetics of nanoparticles must be controlled tightly. However, actual drug release kinetics of nanoparticles cannot be readily measured due to technique difficulties, although various methods have been attempted. Among existing experimental approaches, dialysis method is the most widely applied one due to its simplicity and avoidance of separating released drug from the nanoparticles. Yet this method only measures the released drug in the medium outside a dialysis device (the receiver), instead of actual drug release from the nanoparticles inside the dialysis device (the donor). Thus we proposed a new method using numerical deconvolution to evaluate actual drug release kinetics of nanoparticles inside the donor based on experimental release profiles of nanoparticles and free drug solution in the receptor determined by existing dialysis tests. Two computer programs were developed based on two different numerical methods, namely least square criteria with prescribed Weibull function or orthogonal polynomials as input function. The former was used for all analyses in this work while the latter for verifying the reliability of the predictions. Experimental data of drug release from various nanoparticle formulations obtained from different dialysis settings and membrane pore sizes were used to substantiate this approach. The results demonstrated that this method is applicable to a broad range of nanoparticle and microparticle formulations requiring no additional experiments. It is independent of particle formulations, drug release mechanisms, and testing conditions. This new method may also be used, in combination with existing dialysis devices, to develop a standardized method for quality control, in vitro-in vivo correlation, and for development of nanoparticles and other types of dispersion formulations. Copyright

  6. Artesunate-loaded chitosan/lecithin nanoparticles: preparation, characterization, and in vivo studies.

    Science.gov (United States)

    Chadha, Renu; Gupta, Sushma; Pathak, Natasha

    2012-12-01

    Artesunate (AST), the most widely used artemisnin derivative, has poor aqueous solubility and suffers from low oral bioavailability (~40%). Under these conditions, nanoparticles with controlled and sustained released properties can be a suitable solution for improving its biopharmaceuticals properties. This work reports the preparation and characterization of auto-assembled chitosan/lecithin nanoparticles loaded with AST and AST complexed with β-cyclodextrin (β-CD) to boost its antimalarial activity. The nanoparticles prepared by direct injection of lecithin alcoholic solution into chitosan/water solution have shown the particle size distribution below 300 nm. Drug entrapment efficiency was found to be maximum (90%) for nanoparticles containing 100 mg of AST. Transmission electron microscopy images show spherical shape with contrasted corona (chitosan) surrounded by a lipidic core (lecithin + isopropyl myristate). Differential scanning calorimeter thermograms demonstrated the presence of drug in drug-loaded nanoparticles along with the disappearance of decomposition exotherm suggesting the increased physical stability of drug in prepared formulations. Negligible changes in the characteristic peaks of drug in Fourier-transform infrared spectra indicated the absence of any interaction among the various components entrapped in the nanoparticle formulation. In vitro drug release behavior was found to be influenced by pH value. Increased in vivo antimalarial activity in terms of less mean percent parasitemia was observed in infected Plasmodium berghei mice after the oral administration of all the prepared nanoparticle formulations.

  7. Atomic force microscopy imaging of polyurethane nanoparticles onto different solid substrates

    Energy Technology Data Exchange (ETDEWEB)

    Beddin Fritzen-Garcia, Mauricia [Laboratorio de Bioenergetica e Bioquimica de Macromoleculas, Departamento de Ciencias Farmaceuticas, Universidade Federal de Santa Catarina, 88040-900, Florianopolis, SC (Brazil); POLIMAT, Departamento de Quimica, Universidade Federal de Santa Catarina, 88040-900, Florianopolis, SC (Brazil)], E-mail: maurifritzen@hotmail.com; Giehl Zanetti-Ramos, Betina [Laboratorio de Bioenergetica e Bioquimica de Macromoleculas, Departamento de Ciencias Farmaceuticas, Universidade Federal de Santa Catarina, 88040-900, Florianopolis, SC (Brazil); Schweitzer de Oliveira, Cristian [Laboratorio de Filmes Finos e Superficies, Departamento de Fisica, Universidade Federal de Santa Catarina, 88040-900, Florianopolis, SC (Brazil); Soldi, Valdir [POLIMAT, Departamento de Quimica, Universidade Federal de Santa Catarina, 88040-900, Florianopolis, SC (Brazil); Avelino Pasa, Andre [Laboratorio de Filmes Finos e Superficies, Departamento de Fisica, Universidade Federal de Santa Catarina, 88040-900, Florianopolis, SC (Brazil); Creczynski-Pasa, Tania Beatriz [Laboratorio de Bioenergetica e Bioquimica de Macromoleculas, Departamento de Ciencias Farmaceuticas, Universidade Federal de Santa Catarina, 88040-900, Florianopolis, SC (Brazil)

    2009-03-01

    Atomic force microscopy (AFM) is a technique suited for characterizing nanoparticles on solid surfaces because it offers the capability of 3D visualization and quantitative information about the topography of the samples. In the present work, contact-mode AFM has been applied to imaging polyurethane nanoparticles formulated from a natural triol and isophorone diisocyanate (IPDI) in the presence of poly(ethylene glycol) (PEG). The colloidal polymeric system was deposited on mica, hydrophilic and hydrophobic silicon solid substrates to evaluate the size and shape of the nanoparticles. Our data showed that the nanoparticles were better distributed on mica and hydrophilic silicon. From the analysis of line-scan profiles we obtained different values for the ratio between the diameter and the height of the nanoparticles, indicating that the shape of the particles depends on the interaction between the nanoparticles and the substrate.

  8. Atomic force microscopy imaging of polyurethane nanoparticles onto different solid substrates

    International Nuclear Information System (INIS)

    Beddin Fritzen-Garcia, Mauricia; Giehl Zanetti-Ramos, Betina; Schweitzer de Oliveira, Cristian; Soldi, Valdir; Avelino Pasa, Andre; Creczynski-Pasa, Tania Beatriz

    2009-01-01

    Atomic force microscopy (AFM) is a technique suited for characterizing nanoparticles on solid surfaces because it offers the capability of 3D visualization and quantitative information about the topography of the samples. In the present work, contact-mode AFM has been applied to imaging polyurethane nanoparticles formulated from a natural triol and isophorone diisocyanate (IPDI) in the presence of poly(ethylene glycol) (PEG). The colloidal polymeric system was deposited on mica, hydrophilic and hydrophobic silicon solid substrates to evaluate the size and shape of the nanoparticles. Our data showed that the nanoparticles were better distributed on mica and hydrophilic silicon. From the analysis of line-scan profiles we obtained different values for the ratio between the diameter and the height of the nanoparticles, indicating that the shape of the particles depends on the interaction between the nanoparticles and the substrate

  9. Starch mediated CdS nanoparticles and their photocatalytic performance under visible light irradiation

    International Nuclear Information System (INIS)

    Firdaus, Farha; Faraz, Mohd

    2016-01-01

    Green synthesis of Cadmium Sulphide (CdS-S) nanoparticles is of considerable interest due to its biocompatible and nontoxicity. Here, we present a biomolecule stimulated chemical method was adopted for the successful synthesis of CdS-S nanoparticles using starch as a capping agent. The CdS-S nanoparticles were characterized by various analytical techniques. The CdS-S nanoparicles exhibit photocatalytic activity against methyl orange (MO) at pH 9 in Visible light and the reaction follows pseudo first-order kinetics. The comparative photocatalytic activity revealed that CdS-S nanoparticles remarkably enhanced activities as compared to the commercial TiO 2 nanoparticles. The outcome of these studies offers valuable for planning CdS-S nanoparticles having photocatalytic activities helpful for the formulation of waste water remediation.

  10. Solid lipid nanoparticles suspension versus commercial solutions for dermal delivery of minoxidil.

    Science.gov (United States)

    Padois, Karine; Cantiéni, Céline; Bertholle, Valérie; Bardel, Claire; Pirot, Fabrice; Falson, Françoise

    2011-09-15

    Solid lipid nanoparticles have been reported as possible carrier for skin drug delivery. Solid lipid nanoparticles are produced from biocompatible and biodegradable lipids. Solid lipid nanoparticles made of semi-synthetic triglycerides stabilized with a mixture of polysorbate and sorbitan oleate were loaded with 5% of minoxidil. The prepared systems were characterized for particle size, pH and drug content. Ex vivo skin penetration studies were performed using Franz-type glass diffusion cells and pig ear skin. Ex vivo skin corrosion studies were realized with a method derived from the Corrositex(®) test. Solid lipid nanoparticles suspensions were compared to commercial solutions in terms of skin penetration and skin corrosion. Solid lipid nanoparticles suspensions have been shown as efficient as commercial solutions for skin penetration; and were non-corrosive while commercial solutions presented a corrosive potential. Solid lipid nanoparticles suspensions would constitute a promising formulation for hair loss treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Multiple excitation of supports - Part 1. Formulation

    International Nuclear Information System (INIS)

    Galeao, A.C.N.R.; Barbosa, H.J.C.

    1980-12-01

    The formulation and the solution of a simple specific problem of support movement are presented. The formulation is extended to the general case of infinitesimal elasticity where the approximated solutions are obtained by the variational formulation with spatial discretization by Finite Element Method. Finally, the present usual numerical techniques for the treatment of the resulting ordinary differential equations system are discused: Direct integration, Modal overlap, Spectral response. (E.G.) [pt

  12. Formulation of disperse systems science and technology

    CERN Document Server

    Tadros, Tharwat F

    2014-01-01

    This book presents comprehensively the science and technology behind the formulation of disperse systems like emulsions, suspensions, foams and others. Starting with a general introduction, the book covers a broad range of topics like the role of different classes of surfactants, stability of disperse systems, formulation of different dispersions, evaluation of formulations and many more. Many examples are included, too. Written by the experienced author and editor Tharwart Tadros, this book is indispensable for every scientist working in the field.

  13. O3 Nanoparticles

    KAUST Repository

    Wang, Juan

    2016-11-16

    Ti2O3 nanoparticles with high performance of photothermal conversion are demonstrated for the first time. Benefiting from the nanosize and narrow-bandgap features, the Ti2O3 nanoparticles possess strong light absorption and nearly 100% internal solar–thermal conversion efficiency. Furthermore, Ti2O3 nanoparticle-based thin film shows potential use in seawater desalination and purification.

  14. Biosynthesis of silver nanoparticles.

    Science.gov (United States)

    Poulose, Subin; Panda, Tapobrata; Nair, Praseetha P; Théodore, Thomas

    2014-02-01

    Metal nanoparticles have unique optical, electronic, and catalytic properties. There exist well-defined physical and chemical processes for their preparation. Those processes often yield small quantities of nanoparticles having undesired morphology, and involve high temperatures for the reaction and the use of hazardous chemicals. Relatively, the older technique of bioremediation of metals uses either microorganisms or their components for the production of nanoparticles. The nanoparticles obtained from bacteria, fungi, algae, plants and their components, etc. appear environment-friendly, as toxic chemicals are not used in the processes. In addition to this, the formation of nanoparticles takes place at almost normal temperature and pressure. Control of the shape and size of the nanoparticles is possible by appropriate selection of the pH and temperature. Three important steps are the bioconversion of Ag+ ions, conversion of desired crystals to nanoparticles, and nanoparticle stability. Generally, nanoparticles are characterized by the UV-visible spectroscopy and use of the electron microscope. Silver nanoparticles are used as antimicrobial agents and they possess antifungal, anti-inflammatory, and anti-angiogenic properties. This review highlights the biosynthesis of silver nanoparticles by various organisms, possible mechanisms of their synthesis, their characterization, and applications of silver nanoparticles.

  15. Spray granulation for drug formulation.

    Science.gov (United States)

    Loh, Zhi Hui; Er, Dawn Z L; Chan, Lai Wah; Liew, Celine V; Heng, Paul W S

    2011-12-01

    Granulation is a key unit process in the production of pharmaceutical solid dosage forms and involves the agglomeration of fine particles with the aid of a binding agent. Fluidized bed granulation, a classic example of spray granulation, is a technique of particle agglomeration brought about by the spray addition of the binding liquid onto a stationary bed of powder particles that is transformed to a fluid-like state by the passage of air through it. The basic working principles, equipment set-up, advantages and challenges of fluidized bed granulation are introduced in this review. This is followed by an overview of the formulation and process-related variables affecting granulation performance. Technological advances, particularly in the application of process analytical tools, in the field of fluidized bed granulation research are also discussed. Fluidized bed granulation is a popular technique for pharmaceutical production, as it is a highly economical and efficient one-pot process. The research and development of process analytical technologies (PAT) has allowed greater process understanding and control to be achieved, even for the lesser known fluidized bed techniques, such as bottom spray and fluidized hot melt granulation. In view of its consistent mixing, as well as continuous and concurrent wetting and drying occurring throughout processing, fluidized bed granulation shows great potential for continuous production although more research is required to fully implement, validate and integrate the PAT tools in a production line.

  16. Policy formulation of public acceptance

    International Nuclear Information System (INIS)

    Kasai, Akihiro

    1978-01-01

    Since 1970, the new policy formulation for public acceptance of the new consideration on the location of electric power generation has been set and applied. The planning and the enforcement being conducted by local public organizations for the local economic build-up with plant location and also the adjustement of the requirements for fishery are two main specific characters in this new policy. The background of this new public acceptance policy, the history and the actual problems about the compensation for the location of power generation plants are reviewed. One new proposal, being recommended by the Policy and Science Laboratory to MITI in 1977 is explained. This is based on the method of promoting the location of power generation plants by public participation placing the redevelopment of regional societies as its basis. The problems concerning the industrial structures in farm villages, fishing villages and the areas of commerce and industry should be systematized, and explained from the viewpoint of outside impact, the characteristics of local areas and the location problems in this new proposal. Finally, the location process and its effectiveness should be put in order. (Nakai, Y.)

  17. Slag-based saltstone formulations

    International Nuclear Information System (INIS)

    Langton, C.A.

    1987-01-01

    Approximately 400 x 10 6 liters of low-level alkaline salt solution will be treated at the Savannah River Plant (SRP) Defense Waste Processing Facility (DWPF) prior to disposal in concrete vaults at SRP. Treatment involves removal of CS + and Sr +2 followed by solidification and stabilization of potential contaminants in saltstone, a hydrated ceramic waste form. Chromium, technetium, and nitrate releases from saltstone can be significantly reduced by substituting hydraulic blast furnace slag for portland cement in the formulation designs. Slag-based mixes are also compatible with Class F fly ash used in saltstone as a functional extender to control heat of hydration and reduce permeability. A monolithic waste form is produced by the hydration of the slag and fly ash. Soluble ion release (NO 3 - ) is controlled by the saltstone microstructure. Chromium and technetium are less leachable from slag mixes compared to cement-based waste forms because these species are chemically reduced to a lower valence state by ferrous iron in the slag and precipitated as relatively insoluble phases, such as CR(OH) 3 and TcO 2 . 5 refs., 4 figs., 4 tabs

  18. Pediatric drug development: formulation considerations.

    Science.gov (United States)

    Ali, Areeg Anwer; Charoo, Naseem Ahmad; Abdallah, Daud Baraka

    2014-10-01

    Absence of safe, effective and appropriate treatment is one of the main causes of high mortality and morbidity rates among the pediatric group. This review provides an overview of pharmacokinetic differences between pediatric and adult population and their implications in pharmaceutical development. Different pediatric dosage forms, their merits and demerits are discussed. Food and Drug Administration Act of 1997 and the Best Pharmaceuticals for Children Act 2002 added 6 months patent extension and exclusivity incentives to pharmaceutical companies for evaluation of medicinal products in children. Prescription Drug User Fee Act and Food and Drug Administration Amendments Act of 2007 made it mandatory for pharmaceutical companies to perform pediatric clinical studies on new drug products. Drug development program should include additional clinical bridge studies to evaluate differences in pharmacokinetics and pharmacodynamics of drugs in adult and child populations. Additionally, pharmaceutical development should consider ease of administration, palatability, appropriate excipients, stability and therapeutic equivalency of pediatric dosage forms. Pediatric population is diverse with individual preferences and demand for custom made dosage formulations. Practically it is not feasible to have different pharmaceutical dosage forms for each group. Hence, an appropriate dosage form that can be administered across pediatric population is warranted.

  19. Development of polycationic amphiphilic cyclodextrin nanoparticles for anticancer drug delivery

    Directory of Open Access Journals (Sweden)

    Gamze Varan

    2017-07-01

    Full Text Available Background: Paclitaxel is a potent anticancer drug that is effective against a wide spectrum of cancers. To overcome its bioavailability problems arising from very poor aqueous solubility and tendency to recrystallize upon dilution, paclitaxel is commercially formulated with co-solvents such as Cremophor EL® that are known to cause serious side effects during chemotherapy. Amphiphilic cyclodextrins are favored oligosaccharides as drug delivery systems for anticancer drugs, having the ability to spontaneously form nanoparticles without surfactant or co-solvents. In the past few years, polycationic, amphiphilic cyclodextrins were introduced as effective agents for gene delivery in the form of nanoplexes. In this study, the potential of polycationic, amphiphilic cyclodextrin nanoparticles were evaluated in comparison to non-ionic amphiphilic cyclodextrins and core–shell type cyclodextrin nanoparticles for paclitaxel delivery to breast tumors. Pre-formulation studies were used as a basis for selecting the suitable organic solvent and surfactant concentration for the novel polycationic cyclodextrin nanoparticles. The nanoparticles were then extensively characterized with particle size distribution, polydispersity index, zeta potential, drug loading capacity, in vitro release profiles and cytotoxicity studies.Results: Paclitaxel-loaded cyclodextrin nanoparticles were obtained in the diameter range of 80−125 nm (depending on the nature of the cyclodextrin derivative where the smallest diameter nanoparticles were obtained with polycationic (PC βCDC6. A strong positive charge also helped to increase the loading capacity of the nanoparticles with paclitaxel up to 60%. Interestingly, cyclodextrin nanoparticles were able to stabilize paclitaxel in aqueous solution for 30 days. All blank cyclodextrin nanoparticles were demonstrated to be non-cytotoxic against L929 mouse fibroblast cell line. In addition, paclitaxel-loaded nanoparticles have a

  20. Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Warangkana Lohcharoenkal

    2014-01-01

    Full Text Available Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.

  1. Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

    Science.gov (United States)

    Lohcharoenkal, Warangkana; Wang, Liying; Chen, Yi Charlie

    2014-01-01

    Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy. PMID:24772414

  2. Gelatin modified lipid nanoparticles for anti- viral drug delivery.

    Science.gov (United States)

    K S, Joshy; S, Snigdha; Kalarikkal, Nandakumar; Pothen, Laly A; Thomas, Sabu

    2017-10-01

    The major challenges to clinical application of zidovudine are its moderate aqueous solubility and relative short half-life and serious side effects due to frequent administrations. We investigated the preparation of zidovudine-loaded nanoparticles based on lipids which were further modified with the polymer gelatin. Formulation and stability of the modified nanoparticles were analysed from the physico-chemical characterizations. The interactions of nanoparticles with blood components were tested by haemolysis and aggregation studies. The drug content and entrapment efficiencies were assessed by UV analysis. The effect of nanoparticles on protein adsorption was assessed by native polyacrylamide gel electrophoresis (PAGE). In vitro release studies showed a sustained release profile of zidovudine. In vitro cytotoxicity and cellular uptake of the zidovudine-loaded nanoparticles were performed in MCF-7 and neuro 2a brain cells. The enhanced cellular internalization of drug loaded modified nanoparticles in both the cell lines were revealed by fluorescence microscopy. Hence the present study focuses on the feasibility of zidovudine-loaded polymer modified lipid nanoparticles as carriers for safe and efficient HIV/AIDS therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Synthesis of berberine loaded polymeric nanoparticles by central composite design

    Science.gov (United States)

    Mehra, Meenakshi; Sheorain, Jyoti; Kumari, Santosh

    2016-04-01

    Berberine is an isoquinoline alkaloid which is extracted from bark and roots of Berberis vulgaris plant. It has been used in ayurvedic medicine as it possess antimicrobial, antidiabetic, anticancer, antioxidant properties etc. But poor solubility of berberine leads to poor stability and bioavailability in medical formulations decreasing its efficacy. Hence nanoformulations of berberine can help in removing the limiting factors of alkaloid enhancing its utilization in pharmaceutical industry. Sodium alginate polymer was used to encapsulate berberine within nanoparticles by emulsion solvent evaporation method using tween 80 as a surfactant. Two factors and three level in central composite design was used to study the formulation. The optimized formulation (1% v/v of Tween 80 and 0.01% w/v of sodium alginate) of polymeric nanoparticles was taken for further evaluations. The size of synthesized nanoparticles was found to be 71.18 nm by particle size analysis (PSA). The berberine loaded polymeric nanoparticles showed better antibacterial activity compared to aqueous solution of berberine by well diffusion assay.

  4. Potential of nanoparticles for allergen-specific immunotherapy - use of silica nanoparticles as vaccination platform.

    Science.gov (United States)

    Scheiblhofer, Sandra; Machado, Yoan; Feinle, Andrea; Thalhamer, Josef; Hüsing, Nicola; Weiss, Richard

    2016-12-01

    Allergen-specific immunotherapy is the only curative approach for the treatment of allergies. There is an urgent need for improved therapies, which increase both, efficacy and patient compliance. Novel routes of immunization and the use of more advanced vaccine platforms have gained heightened interest in this field. Areas covered: The current status of allergen-specific immunotherapy is summarized and novel routes of immunization and their challenges in the clinics are critically discussed. The use of nanoparticles as novel delivery system for allergy vaccines is comprehensively reviewed. Specifically, the advantages of silica nanoparticles as vaccine carriers and adjuvants are summarized. Expert opinion: Future allergen-specific immunotherapy will combine engineered hypoallergenic vaccines with novel routes of administration, such as the skin. Due to their biodegradability, and the easiness to introduce surface modifications, silica nanoparticles are promising candidates for tailor-made vaccines. By covalently linking allergens and polysaccharides to silica nanoparticles, a versatile vaccination platform can be designed to specifically target antigen-presenting cells, render the formulation hypoallergenic, and introduce immunomodulatory functions. Combining potent skin vaccination methods, such as fractional laser ablation, with nanoparticle-based vaccines addresses all the requirements for safe and efficient therapy of allergic diseases.

  5. Assessing Nanoparticle Toxicity

    Science.gov (United States)

    Love, Sara A.; Maurer-Jones, Melissa A.; Thompson, John W.; Lin, Yu-Shen; Haynes, Christy L.

    2012-07-01

    Nanoparticle toxicology, an emergent field, works toward establishing the hazard of nanoparticles, and therefore their potential risk, in light of the increased use and likelihood of exposure. Analytical chemists can provide an essential tool kit for the advancement of this field by exploiting expertise in sample complexity and preparation as well as method and technology development. Herein, we discuss experimental considerations for performing in vitro nanoparticle toxicity studies, with a focus on nanoparticle characterization, relevant model cell systems, and toxicity assay choices. Additionally, we present three case studies (of silver, titanium dioxide, and carbon nanotube toxicity) to highlight the important toxicological considerations of these commonly used nanoparticles.

  6. Photocatalytic degradation of the Paracetamol drug using Lanthanum doped ZnO nanoparticles and their in-vitro cytotoxicity assay

    Energy Technology Data Exchange (ETDEWEB)

    Shakir, Mohammad, E-mail: shakir078@yahoo.com [Department of Chemistry, Aligarh Muslim University, Aligarh 202002 (India); Faraz, Mohd [Department of Chemistry, Aligarh Muslim University, Aligarh 202002 (India); Sherwani, Mohd Asif [Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002 (India); Al-Resayes, Saud I. [Department of Chemistry, College of Science, King Saud University, Riyadh 11451 (Saudi Arabia)

    2016-08-15

    The doping of semiconductor by rare earth metals nanoparticles is an effective way for increasing photocatalytic activity. Zinc oxide and Lanthanum doped Zinc oxide nanoparticles were synthesized by modifying the gel-combustion method. It was found that La can greatly enhance the cytotoxicity and photocatalytic activity of ZnO nanoparticles towards various cell lines and Paracetamol drug. These nanoparticles were characterized by various spectroscopic and other techniques which clearly revealed the presence of lanthanum ions. The absorption edge shifts towards the visible region after doping with La ions. This shift shows that the doping of La ions is favorable for absorbing the visible light. The comparative photocatalytic and cytotoxicity activity revealed that La doped ZnO nanoparticles remarkably enhanced activities as compared to the ZnO nanoparticles. The outcome of these studies offers valuable for planning La doped ZnO nanoparticles having cytotoxicity and photocatalytic activities helpful for the formulation of anticancer product and waste water remediation.

  7. Glass Ceramic Formulation Data Package

    Energy Technology Data Exchange (ETDEWEB)

    Crum, Jarrod V.; Rodriguez, Carmen P.; McCloy, John S.; Vienna, John D.; Chung, Chul-Woo

    2012-06-17

    A glass ceramic waste form is being developed for treatment of secondary waste streams generated by aqueous reprocessing of commercial used nuclear fuel (Crum et al. 2012b). The waste stream contains a mixture of transition metals, alkali, alkaline earths, and lanthanides, several of which exceed the solubility limits of a single phase borosilicate glass (Crum et al. 2009; Caurant et al. 2007). A multi-phase glass ceramic waste form allows incorporation of insoluble components of the waste by designed crystallization into durable heat tolerant phases. The glass ceramic formulation and processing targets the formation of the following three stable crystalline phases: (1) powellite (XMoO4) where X can be (Ca, Sr, Ba, and/or Ln), (2) oxyapatite Yx,Z(10-x)Si6O26 where Y is alkaline earth, Z is Ln, and (3) lanthanide borosilicate (Ln5BSi2O13). These three phases incorporate the waste components that are above the solubility limit of a single-phase borosilicate glass. The glass ceramic is designed to be a single phase melt, just like a borosilicate glass, and then crystallize upon slow cooling to form the targeted phases. The slow cooling schedule is based on the centerline cooling profile of a 2 foot diameter canister such as the Hanford High-Level Waste canister. Up to this point, crucible testing has been used for glass ceramic development, with cold crucible induction melter (CCIM) targeted as the ultimate processing technology for the waste form. Idaho National Laboratory (INL) will conduct a scaled CCIM test in FY2012 with a glass ceramic to demonstrate the processing behavior. This Data Package documents the laboratory studies of the glass ceramic composition to support the CCIM test. Pacific Northwest National Laboratory (PNNL) measured melt viscosity, electrical conductivity, and crystallization behavior upon cooling to identify a processing window (temperature range) for melter operation and cooling profiles necessary to crystallize the targeted phases in the

  8. Cytocompatible antifungal acrylic resin containing silver nanoparticles for dentures

    Science.gov (United States)

    Acosta-Torres, Laura Susana; Mendieta, Irasema; Nuñez-Anita, Rosa Elvira; Cajero-Juárez, Marcos; Castaño, Víctor M

    2012-01-01

    Background Inhibition of Candida albicans on denture resins could play a significant role in preventing the development of denture stomatitis. The safety of a new dental material with antifungal properties was analyzed in this work. Methods Poly(methyl methacrylate) [PMMA] discs and PMMA-silver nanoparticle discs were formulated, with the commercial acrylic resin, Nature-CrylTM, used as a control. Silver nanoparticles were synthesized and characterized by ultraviolet-visible spectroscopy, dispersive Raman spectroscopy, and transmission electron microscopy. The antifungal effect was assessed using a luminescent microbial cell viability assay. Biocompatibility tests were carried out using NIH-3T3 mouse embryonic fibroblasts and a Jurkat human lymphocyte cell line. Cells were cultured for 24 or 72 hours in the presence or absence of the polymer formulations and analyzed using three different tests, ie, cellular viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell proliferation by enzyme-linked immunosorbent assay BrdU, and genomic DNA damage (Comet assay). Finally, the samples were evaluated mechanically, and the polymer-bearing silver nanoparticles were analyzed microscopically to evaluate dispersion of the nanoparticles. Results The results show that PMMA-silver nanoparticle discs significantly reduce adherence of C. albicans and do not affect metabolism or proliferation. They also appear not to cause genotoxic damage to cells. Conclusion The present work has developed a new biocompatible antifungal PMMA denture base material. PMID:22969297

  9. Cytocompatible antifungal acrylic resin containing silver nanoparticles for dentures.

    Science.gov (United States)

    Acosta-Torres, Laura Susana; Mendieta, Irasema; Nuñez-Anita, Rosa Elvira; Cajero-Juárez, Marcos; Castaño, Víctor M

    2012-01-01

    Inhibition of Candida albicans on denture resins could play a significant role in preventing the development of denture stomatitis. The safety of a new dental material with antifungal properties was analyzed in this work. Poly(methyl methacrylate) [PMMA] discs and PMMA-silver nanoparticle discs were formulated, with the commercial acrylic resin, Nature-Cryl™, used as a control. Silver nanoparticles were synthesized and characterized by ultraviolet-visible spectroscopy, dispersive Raman spectroscopy, and transmission electron microscopy. The antifungal effect was assessed using a luminescent microbial cell viability assay. Biocompatibility tests were carried out using NIH-3T3 mouse embryonic fibroblasts and a Jurkat human lymphocyte cell line. Cells were cultured for 24 or 72 hours in the presence or absence of the polymer formulations and analyzed using three different tests, ie, cellular viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell proliferation by enzyme-linked immunosorbent assay BrdU, and genomic DNA damage (Comet assay). Finally, the samples were evaluated mechanically, and the polymer-bearing silver nanoparticles were analyzed microscopically to evaluate dispersion of the nanoparticles. The results show that PMMA-silver nanoparticle discs significantly reduce adherence of C. albicans and do not affect metabolism or proliferation. They also appear not to cause genotoxic damage to cells. The present work has developed a new biocompatible antifungal PMMA denture base material.

  10. Preparation and characterization of carvacrol loaded polyhydroxybutyrate nanoparticles by nanoprecipitation and dialysis methods.

    Science.gov (United States)

    Shakeri, Fatemeh; Shakeri, Shahryar; Hojjatoleslami, Mohammad

    2014-04-01

    In this investigation, preparation of carvacrol loaded polyhydroxybutyrate (PHB) nanoparticles was performed by nanoprecipitation and dialysis methods. PHB particles were obtained by nanoprecipitation method without and with low concentration of Tween 80 or pluronic as surfactant. Nano- and micro-sized particles were formed with trimodal distribution and large aggregates. Size and distribution of nanoparticles were decreased when concentration of Tween 80 was increased to 1% (v/v) in water as polar phase. PHB nanoparticles had narrow size (157 nm) with monomodal distribution. Nanoparticles, which were prepared by dialysis method had 140 nm in diameter with monomodal distribution. Carvacrol was used as a lipophilic drug and entrapped in optimized nanoparticles formulation by nanoprecipitation and dialysis methods. Entrapment efficacy was 21% and 11%, respectively. Morphology of PHB nanoparticles was spherical. The results of kinetic release study showed that carvacrol was released for at least 3 days. Release kinetic parameters showed a simple Fickian diffusion behavior for both formulations. Carvacrol loaded PHB nanoparticles had good dispersion into the agar medium and antimicrobial activity against Escherichia coli. This study describes the 1st work on loading of carvacrol into the PHB nanoparticles by nanoprecipitation and dialysis methods. © 2014 Institute of Food Technologists®

  11. Optimization of {beta}-carotene loaded solid lipid nanoparticles preparation using a high shear homogenization technique

    Energy Technology Data Exchange (ETDEWEB)

    Triplett, Michael D., E-mail: triplettm@battelle.or [Battelle Memorial Institute, Health and Life Sciences Global Business (United States); Rathman, James F. [The Ohio State University, Department of Chemical and Biomolecular Engineering (United States)

    2009-04-15

    Using statistical experimental design methodologies, the solid lipid nanoparticle design space was found to be more robust than previously shown in literature. Formulation and high shear homogenization process effects on solid lipid nanoparticle size distribution, stability, drug loading, and drug release have been investigated. Experimentation indicated stearic acid as the optimal lipid, sodium taurocholate as the optimal cosurfactant, an optimum lecithin to sodium taurocholate ratio of 3:1, and an inverse relationship between mixing time and speed and nanoparticle size and polydispersity. Having defined the base solid lipid nanoparticle system, {beta}-carotene was incorporated into stearic acid nanoparticles to investigate the effects of introducing a drug into the base solid lipid nanoparticle system. The presence of {beta}-carotene produced a significant effect on the optimal formulation and process conditions, but the design space was found to be robust enough to accommodate the drug. {beta}-Carotene entrapment efficiency averaged 40%. {beta}-Carotene was retained in the nanoparticles for 1 month. As demonstrated herein, solid lipid nanoparticle technology can be sufficiently robust from a design standpoint to become commercially viable.

  12. Еvaluation of biocompatibility and antioxidant efficiency of chitosan-alginate nanoparticles loaded with quercetin.

    Science.gov (United States)

    Aluani, Denitsa; Tzankova, Virginia; Kondeva-Burdina, Magdalena; Yordanov, Yordan; Nikolova, Elena; Odzhakov, Feodor; Apostolov, Alexandar; Markova, Tzvetanka; Yoncheva, Krassimira

    2017-10-01

    The present study deals with development and evaluation of the safety profile of chitosan/alginate nanoparticles as a platform for delivery of a natural antioxidant quercetin. The nanoparticles were prepared by varying the ratios between both biopolymers giving different size and charge of the formulations. The biocompatibility was explored in vitro in cells from different origin: cultivated HepG2 cells, isolated primary rat hepatocytes, isolated murine spleen lymphocytes and macrophages. In vivo toxicological evaluation was performed after repeated 14-day oral administration to rats. The study revealed that chitosan/alginate nanoparticles did not change body weight, the relative weight of rat livers, liver histology, hematology and biochemical parameters. The protective effects of quercetin-loaded nanoparticles were investigated in the models of iron/ascorbic acid (Fe 2+ /AA) induced lipid peroxidation in microsomes and tert-butyl hydroperoxide oxidative stress in isolated rat hepatocytes. Interesting finding was that the empty chitosan/alginate nanoparticles possessed protective activity themselves. The antioxidant effects of quercetin loaded into the nanoparticles formulated with higher concentration of chitosan were superior compared to quercetin encapsulated in nanoparticles with higher amount of sodium alginate. In conclusion, chitosan/alginate nanoparticles can be considered appropriate carrier for quercetin, combining safety profile and improved protective activity of the encapsulated antioxidant. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Optimization of β-carotene loaded solid lipid nanoparticles preparation using a high shear homogenization technique

    International Nuclear Information System (INIS)

    Triplett, Michael D.; Rathman, James F.

    2009-01-01

    Using statistical experimental design methodologies, the solid lipid nanoparticle design space was found to be more robust than previously shown in literature. Formulation and high shear homogenization process effects on solid lipid nanoparticle size distribution, stability, drug loading, and drug release have been investigated. Experimentation indicated stearic acid as the optimal lipid, sodium taurocholate as the optimal cosurfactant, an optimum lecithin to sodium taurocholate ratio of 3:1, and an inverse relationship between mixing time and speed and nanoparticle size and polydispersity. Having defined the base solid lipid nanoparticle system, β-carotene was incorporated into stearic acid nanoparticles to investigate the effects of introducing a drug into the base solid lipid nanoparticle system. The presence of β-carotene produced a significant effect on the optimal formulation and process conditions, but the design space was found to be robust enough to accommodate the drug. β-Carotene entrapment efficiency averaged 40%. β-Carotene was retained in the nanoparticles for 1 month. As demonstrated herein, solid lipid nanoparticle technology can be sufficiently robust from a design standpoint to become commercially viable.

  14. Chemicals-Based Formulation Design: Virtual Experimentations

    DEFF Research Database (Denmark)

    Conte, Elisa; Gani, Rafiqul

    2011-01-01

    This paper presents a systematic procedure for virtual experimentations related to the design of liquid formulated products. All the experiments that need to be performed when designing a liquid formulated product (lotion), such as ingredients selection and testing, solubility tests, property...... measurements, can now be performed through the virtual Product-Process Design laboratory [[1], [2] and [3

  15. Colorimetric analysis of hexachlorophene in topical formulations.

    Science.gov (United States)

    French, W N; Matsui, F; Smith, S J; Wood, R J

    1975-01-01

    The commonly used 4-aminoantipyrine dye formation procedure for hexachlorophene analysis in topical formulations was modified to overcome interference due to other components. Bar soaps and nonemulsion formulations are analyzed directly, employing a chloroform back-extraction stage of the dye prior to quantitation. Hexachlorophene in emulsions and liquid soaps is determined using a TLC separation prior to dye formation.

  16. 40 CFR 152.43 - Alternate formulations.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Alternate formulations. 152.43 Section 152.43 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Registration Procedures § 152.43 Alternate formulations...

  17. Formulation and characterization of modified release tablets ...

    African Journals Online (AJOL)

    Formulation with 35% polymer content exhibited zero order release profile and it released 35% of the drug in first hr, later on, controlled drug release was observed upto the 12th hour. Formulations with PVAc to Na-CMC ratio 20:80 exhibited zero order release pattern at levels of studied concentrations, which suggested that ...

  18. A New Resistance Formulation for Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    Ji-Huan He

    2008-01-01

    Full Text Available A new resistance formulation for carbon nanotubes is suggested using fractal approach. The new formulation is also valid for other nonmetal conductors including nerve fibers, conductive polymers, and molecular wires. Our theoretical prediction agrees well with experimental observation.

  19. Silver nanoparticles in dentistry.

    Science.gov (United States)

    Noronha, Victor T; Paula, Amauri J; Durán, Gabriela; Galembeck, Andre; Cogo-Müller, Karina; Franz-Montan, Michelle; Durán, Nelson

    2017-10-01

    Silver nanoparticles (AgNPs) have been extensively studied for their antimicrobial properties, which provide an extensive applicability in dentistry. Because of this increasing interest in AgNPs, the objective of this paper was to review their use in nanocomposites; implant coatings; pre-formulation with antimicrobial activity against cariogenic pathogens, periodontal biofilm, fungal pathogens and endodontic bacteria; and other applications such as treatment of oral cancer and local anesthesia. Recent achievements in the study of the mechanism of action and the most important toxicological aspects are also presented. Systematic searches were carried out in Web of Science (ISI), Google, PubMed, SciFinder and EspaceNet databases with the keywords "silver nano* or AgNP*" and "dentist* or dental* or odontol*". A total of 155 peer-reviewed articles were reviewed. Most of them were published in the period of 2012-2017, demonstrating that this topic currently represents an important trend in dentistry research. In vitro studies reveal the excellent antimicrobial activity of AgNPs when associated with dental materials such as nanocomposites, acrylic resins, resin co-monomers, adhesives, intracanal medication, and implant coatings. Moreover, AgNPs were demonstrated to be interesting tools in the treatment of oral cancers due to their antitumor properties. The literature indicates that AgNPs are a promising system with important features such as antimicrobial, anti-inflammatory and antitumor activity, and a potential carrier in sustained drug delivery. However, there are some aspects of the mechanisms of action of AgNPs, and some important toxicological aspects arising from the use of this system that must be completely elucidated. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  20. De-alloyed platinum nanoparticles

    Science.gov (United States)

    Strasser, Peter [Houston, TX; Koh, Shirlaine [Houston, TX; Mani, Prasanna [Houston, TX; Ratndeep, Srivastava [Houston, TX

    2011-08-09

    A method of producing de-alloyed nanoparticles. In an embodiment, the method comprises admixing metal precursors, freeze-drying, annealing, and de-alloying the nanoparticles in situ. Further, in an embodiment de-alloyed nanoparticle formed by the method, wherein the nanoparticle further comprises a core-shell arrangement. The nanoparticle is suitable for electrocatalytic processes and devices.

  1. Surface coating mediates the toxicity of polymeric nanoparticles towards human-like macrophages.

    Science.gov (United States)

    Grabowski, Nadège; Hillaireau, Hervé; Vergnaud, Juliette; Tsapis, Nicolas; Pallardy, Marc; Kerdine-Römer, Saadia; Fattal, Elias

    2015-03-30

    The purpose of this study was to investigate the toxicity of a series of poly(lactide-co-glycolic) (PLGA) nanoparticles on human-like THP-1 macrophages. Positively-, negatively-charged and neutral nanoparticles (200 nm) were prepared using chitosan (CS), poloxamer 188 (PF68) and poly(vinyl alcohol) (PVA) as stabilizer. Stabilizer-free PLGA nanoparticles were obtained as well. When used at therapeutically relevant concentrations (up to 0.1 mg/mL in vitro), all tested nanoparticles showed no or scarce signs of toxicity, as assessed by cell mitochondrial activity, induction of apoptosis and necrosis, production of intracellular reactive oxygen species (ROS) and secretion of pro-inflammatory cytokines. At high concentrations (above 1mg/mL), cytotoxicity was found to be induced by the presence of stabilizers, whatever the toxicological pattern of the stabilizer itself. While stabilizer-free PLGA nanoparticles exerted no cytotoxicity, the slightly cytotoxic CS polymer conferred PLGA nanoparticles significant cytotoxicity when used as nanoparticle stabilizer; more surprisingly, the otherwise innocuous PVA and PF68 polymers also conferred a significant cytotoxicity to PLGA nanoparticles. These results unveiled the critical toxicological contribution played by stabilizers used for the formulation of PLGA nanoparticles when used at high concentrations, which may have implications for local toxicities of PLGA-based nanomedicine, and provided additional insight in cytotoxic effects of internalized nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Cu-Ag core-shell nanoparticles with enhanced oxidation stability for printed electronics.

    Science.gov (United States)

    Lee, Changsoo; Kim, Na Rae; Koo, Jahyun; Lee, Yung Jong; Lee, Hyuck Mo

    2015-11-13

    In this work, we synthesized uniform Cu-Ag core-shell nanoparticles using a facile two-step process that consists of thermal decomposition and galvanic displacement methods. The core-shell structure of these nanoparticles was confirmed through characterization using transmission electron microscopy, energy-dispersive spectroscopy, and x-ray diffraction. Furthermore, we investigated the oxidation stability of the Cu-Ag core-shell nanoparticles in detail. Both qualitative and quantitative x-ray photoelectron spectroscopy analyses confirm that the Cu-Ag core-shell nanoparticles have considerably higher oxidation stability than Cu nanoparticles. Finally, we formulated a conductive ink using the synthesized nanoparticles and coated it onto glass substrates. Following the sintering process, we compared the resistivity of the Cu-Ag core-shell nanoparticles with that of the Cu nanoparticles. The results of this study clearly show that the Cu-Ag core-shell nanoparticles can potentially be used as an alternative to Ag nanoparticles because of their superior oxidation stability and electrical properties.

  3. Characterization of nanoparticle-lipid membrane interactions using QCM-D.

    Science.gov (United States)

    Frost, Rickard; Svedhem, Sofia

    2013-01-01

    In vitro characterization of nanoparticles is becoming increasingly important due to the rapid development of novel nanoparticle formulations for applications in the field of nanomedicine and related areas. Commonly, nanoparticles are simply characterized with respect to their size and zeta potential, and additional in vitro characterization of nanoparticles is needed to develop useful nanoparticle structure-activity relationships. In this context it is highly interesting to characterize the interactions between nanoparticles and model interfaces, such as lipid membranes. Here, we describe a methodology to study such interactions using the quartz crystal microbalance with dissipation monitoring technique (QCM-D). In order to mimic some aspects of the native cell membrane, a supported lipid membrane is formed on the QCM-D sensor surface. Subsequently the membrane is exposed to nanoparticles, and the nanoparticle-lipid membrane interactions are monitored in real time. The outcome of such analysis provides information on the adsorption process (importantly kinetics and adsorbed amounts) as well as on the integrity of both the nanoparticles and the lipid membrane upon interaction. QCM-D analyses are suitable for screening of nanoparticle-lipid membrane interactions due to the fair throughput of the technique, which can be complemented, when needed, by additional analyses by other surface-sensitive analytical techniques.

  4. In Vivo Assessment of Clobetasol Propionate-Loaded Lecithin-Chitosan Nanoparticles for Skin Delivery

    Directory of Open Access Journals (Sweden)

    Taner Şenyiğit

    2016-12-01

    Full Text Available The aim of this work was to assess in vivo the anti-inflammatory efficacy and tolerability of clobetasol propionate (CP loaded lecithin/chitosan nanoparticles incorporated into chitosan gel for topical application (CP 0.005%. As a comparison, a commercial cream (CP 0.05% w/w, and a sodium deoxycholate gel (CP 0.05% w/w were also evaluated. Lecithin/chitosan nanoparticles were prepared by self-assembling of the components obtained by direct injection of soybean lecithin alcoholic solution containing CP into chitosan aqueous solution. Nanoparticles obtained had a particle size around 250 nm, narrow distribution (polydispersity index below 0.2 and positive surface charge, provided by a superficial layer of the cationic polymer. The nanoparticle suspension was then loaded into a chitosan gel, to obtain a final CP concentration of 0.005%. The anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema test on Wistar rats, the effect of formulations on the barrier property of the stratum corneum were determined using transepidermal water loss measurements (TEWL and histological analysis was performed to evaluate the possible presence of morphological changes. The results obtained indicate that nanoparticle-in-gel formulation produced significantly higher edema inhibition compared to other formulations tested, although it contained ten times less CP. TEWL measurements also revealed that all formulations have no significant disturbance on the barrier function of skin. Furthermore, histological analysis of rat abdominal skin did not show morphological tissue changes nor cell infiltration signs after application of the formulations. Taken together, the present data show that the use of lecithin/chitosan nanoparticles in chitosan gel as a drug carrier significantly improves the risk-benefit ratio as compared with sodium-deoxycholate gel and commercial cream formulations of CP.

  5. Comprehensive study of the drug delivery properties of poly(l-lactide)-poly(ethylene glycol) nanoparticles in rats and tumor-bearing mice.

    Science.gov (United States)

    Shalgunov, Vladimir; Zaytseva-Zotova, Daria; Zintchenko, Arkadi; Levada, Tatiana; Shilov, Yuri; Andreyev, Dmitry; Dzhumashev, Dzhangar; Metelkin, Evgeny; Urusova, Alexandra; Demin, Oleg; McDonnell, Kevin; Troiano, Greg; Zale, Stephen; Safarovа, Elmira

    2017-09-10

    Nanoparticles made of polylactide-poly(ethylene glycol) block-copolymer (PLA-PEG) are promising vehicles for drug delivery due to their biodegradability and controllable payload release. However, published data on the drug delivery properties of PLA-PEG nanoparticles are heterogeneous in terms of nanoparticle characteristics and mostly refer to low injected doses (a few mg nanoparticles per kg body weight). We have performed a comprehensive study of the biodistribution of nanoparticle formulations based on PLA-PEG nanoparticles of ~100nm size at injected doses of 30 to 140mg/kg body weight in healthy rats and nude tumor-bearing mice. Nanoparticle formulations differed by surface PEG coverage and by release kinetics of the encapsulated model active pharmaceutical ingredient (API). Increase in PEG coverage prolonged nanoparticle circulation half-life up to ~20h in rats and ~10h in mice and decreased retention in liver, spleen and lungs. Circulation half-life of the encapsulated API grew monotonously as the release rate slowed down. Plasma and tissue pharmacokinetics was dose-linear for inactive nanoparticles, but markedly dose-dependent for the model therapeutic formulation, presumably because of the toxic effects of released API. A mathematical model of API distribution calibrated on the data for inactive nanoparticles and conventional API form correctly predicted the distribution of the model therapeutic formulation at the lowest investigated dose, but for higher doses the toxic action of the released API had to be explicitly modelled. Our results provide a coherent illustration of the ability of controllable-release PLA-PEG nanoparticles to serve as an effective drug delivery platform to alter API biodistribution. They also underscore the importance of physiological effects of released drug in determining the biodistribution of therapeutic drug formulations at doses approaching tolerability limits. Copyright © 2017 The Authors. Published by Elsevier B.V. All

  6. Synthesis of zinc oxide nanoparticles elaborated by microemulsion method

    Energy Technology Data Exchange (ETDEWEB)

    Yildirim, Ozlem Altintas [Department of Metallurgical and Materials Engineering, Middle East Technical University, 06531 Ankara (Turkey); Durucan, Caner, E-mail: cdurucan@metu.edu.t [Department of Metallurgical and Materials Engineering, Middle East Technical University, 06531 Ankara (Turkey)

    2010-09-17

    Graphical abstract: . Display Omitted Research highlights: {yields} Spherical and rod-like ZnO nanostructures obtained in reverse microemulsion. {yields} Morphological variations for microemulsion products with surfactant amount. {yields} Formation mechanism for ZnO nanosructres in a reverse emulsion system. {yields} Optical properties of the ZnO nanoparticles. - Abstract: Zinc oxide (ZnO) nanoparticles were synthesized by a reverse microemulsion system formed from sodium bis(2-ethylhexyl)sulfosuccinate (Aerosol OT, or AOT):glycerol:n-heptane. The zinc precursor was zinc acetate dihydrate. The formation of ZnO nanoparticles was achieved by calcination of premature zinc glycerolate microemulsion product in air at 300, 400 and 500 {sup o}C. The crystal structure and the morphology of the ZnO nanoparticles were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Thermal analysis was employed to reveal structural and chemical changes during calcination. Both surfactant concentrations - AOT - in the initial microemulsion formulation and the calcination temperature influenced the morphology and size of the ZnO nanoparticles. Low surfactant concentrations (5:5:90, AOT:glycerol:n-heptane, wt.%) resulted in formation of spherical ZnO nanoparticles. The average particle size increased from 15 {+-} 1 to 24 {+-} 1 nm with calcination temperature, but spherical morphology remained unchanged after all calcination treatments. The microemulsion system containing higher surfactant amount (30:5:65, AOT:glycerol:n-heptane, wt.%) resulted in rod-like ZnO nanostructures after calcination at 300 and 400 {sup o}C, with a diameter of 22 {+-} 3 and 28 {+-} 1 nm; and with a length of 66 {+-} 3 and 72 {+-} 1 nm, respectively. Further increase in the calcination temperature to 500 {sup o}C initiated rod-to-sphere shape transformation for the ZnO nanoparticles produced using this particular microemulsion formulation. For all ZnO microemulsion products, the

  7. Isotretinoin Oil-Based Capsule Formulation Optimization

    Directory of Open Access Journals (Sweden)

    Pi-Ju Tsai

    2013-01-01

    Full Text Available The purpose of this study was to develop and optimize an isotretinoin oil-based capsule with specific dissolution pattern. A three-factor-constrained mixture design was used to prepare the systemic model formulations. The independent factors were the components of oil-based capsule including beeswax (X1, hydrogenated coconut oil (X2, and soybean oil (X3. The drug release percentages at 10, 30, 60, and 90 min were selected as responses. The effect of formulation factors including that on responses was inspected by using response surface methodology (RSM. Multiple-response optimization was performed to search for the appropriate formulation with specific release pattern. It was found that the interaction effect of these formulation factors (X1X2, X1X3, and X2X3 showed more potential influence than that of the main factors (X1, X2, and X3. An optimal predicted formulation with Y10 min, Y30 min, Y60 min, and Y90 min release values of 12.3%, 36.7%, 73.6%, and 92.7% at X1, X2, and X3 of 5.75, 15.37, and 78.88, respectively, was developed. The new formulation was prepared and performed by the dissolution test. The similarity factor f2 was 54.8, indicating that the dissolution pattern of the new optimized formulation showed equivalence to the predicted profile.

  8. Novel free paclitaxel-loaded poly(L-γ-glutamylglutamine–paclitaxel nanoparticles

    Directory of Open Access Journals (Sweden)

    Danbo Yang

    2011-01-01

    Full Text Available Danbo Yang1, Sang Van2, Xinguo Jiang3, Lei Yu1,21Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, People's Republic of China; 2Biomedical Group, Nitto Denko Technical Corporation, Oceanside, CA, USA; 3School of Pharmacy, Fudan University, Shanghai, People's Republic of ChinaAbstract: The purpose of this study was to develop a novel formulation of paclitaxel (PTX that would improve its therapeutic index. Here, we combined a concept of polymer–PTX drug conjugate with a concept of polymeric micelle drug delivery to form novel free PTX-loaded poly(L-γ-glutamylglutamine (PGG–PTX conjugate nanoparticles. The significance of this drug formulation emphasizes the simplicity, novelty, and flexibility of the method of forming nanoparticles that contain free PTX and conjugated PTX in the same drug delivery system. The results of effectively inhibiting tumor growth in mouse models demonstrated the feasibility of the nanoparticle formulation. The versatility and potential of this dual PTX drug delivery system can be explored with different drugs for different indications. Novel and simple formulations of PTX-loaded PGG–PTX nanoparticles could have important implications in translational medicines.Keywords: paclitaxel, polymeric micelle, poly(L-γ-glutamylglutamine–paclitaxel, nanoconjugate, nanoparticles

  9. Formulation of heat absorbing glasses

    Directory of Open Access Journals (Sweden)

    Álvarez-Casariego, Pedro

    1996-06-01

    Full Text Available In the thermal exchanges between buildings and environment, glazing is an element of major importance, for it largely influences the so-called Solar Heat Gain and Thermal Losses. These parameters can be modified by applying different type of coatings onto glass surface or by adding colorant compounds during glass melting. The latter is a cheaper way to control the Solar Heat Gain. The knowledge of the laws governing the interaction between colorant compounds and solar radiation, allows us to define glass formulations achieving specific aesthetic requirements and solar energy absorption. In this paper two examples of application of the modelling of glass colorants spectral absorptance are presented. First is addressed to obtaining a glass with high luminous transmittance and low solar energy transmittance, and the other one to obtaining a glass with neutral colour appearance and minimized solar energy transmittance. Calculation formulas are defined together with photometric properties so-obtained. These type of glasses are particularly suitable to be used as building and automotive glazing, for they retain the mechanical characteristics and possibilities of transformation of standard glass.

    En los intercambios de energía entre un edificio y el medio exterior, el vidrio es el elemento de mayor importancia, por su influencia en la Ganancia de Calor Solar y en las Pérdidas Térmicas. Estos parámetros pueden ser modificados mediante el depósito de capas sobre el vidrio o mediante la adición de compuestos absorbentes de la radiación solar. Esta última vía es la más económica para controlar la Ganancia de Calor Solar. El conocimiento de las leyes que gobiernan la interacción de los diversos colorantes con la radiación solar, permite definir formulaciones de vidrios con características especificas de tipo estético y de absorción energética. En este trabajo se presentan dos ejemplos de aplicación de esta modelización de las

  10. Enhanced magnetic resonance contrast of iron oxide nanoparticles embedded in a porous silicon nanoparticle host

    Science.gov (United States)

    Kinsella, Joseph; Ananda, Shalini; Andrew, Jennifer; Grondek, Joel; Chien, Miao-Ping; Scandeng, Miriam; Gianneschi, Nathan; Ruoslahti, Erkki; Sailor, Michael

    2013-02-01

    In this report, we prepared a porous Si nanoparticle with a pore morphology that facilitates the proximal loading and alignment of magnetite nanoparticles. We characterized the composite materials using superconducting quantum interference device magnetometry, dynamic light scattering, transmission electron microscopy, and MRI. The in vitro cytotoxicity of the composite materials was tested using cell viability assays on human liver cancer cells and rat hepatocytes. An in vivo analysis using a hepatocellular carcinoma (HCC) Sprague Dawley rat model was used to determine the biodistribution properties of the material, while naïve Sprague Dawley rats were used to determine the pharmocokinetic properties of the nanomaterials. The composite material reported here demonstrates an injectable nanomaterial that exploits the dipolar coupling of superparamagnetic nanoparticles trapped within a secondary inorganic matrix to yield significantly enhanced MRI contrast. This preparation successfully avoids agglomeration issues that plague larger ferromagnetic systems. A Fe3O4:pSi composite formulation consisting of 25% by mass Fe3O4 yields an maximal T2* value of 556 mM Fe-1 s-1. No cellular (HepG2 or rat hepatocyte cells) or in vivo (rat) toxicity was observed with the formulation, which degrades and is eliminated after 4-8 h in vivo. The ability to tailor the magnetic properties of such materials may be useful for in vivo imaging, magnetic hyperthermia, or drug-delivery applications.

  11. Canonical operator formulation of nonequilibrium thermodynamics

    International Nuclear Information System (INIS)

    Mehrafarin, M.

    1992-09-01

    A novel formulation of nonequilibrium thermodynamics is proposed which emphasises the fundamental role played by the Boltzmann constant k in fluctuations. The equivalence of this and the stochastic formulation is demonstrated. The k → 0 limit of this theory yields the classical deterministic description of nonequilibrium thermodynamics. The new formulation possesses unique features which bear two important results namely the thermodynamic uncertainty principle and the quantisation of entropy production rate. Such a theory becomes indispensable whenever fluctuations play a significant role. (author). 7 refs

  12. Preformulation and Formulation of Investigational New Drugs

    Science.gov (United States)

    1985-07-01

    bilock number) -his annual report contains preformulation and formulation studies on WR249,655.2CL’ C141-6s2CI) , WR238,605, WR171,669’HCI...RMI-S ltr, 31 Jul 1992 THIS PAGE IS UNCLASSIFIED O0hK ri~t. GUt*Y . 00 Preformulation and Formulation of Investigational New Drugs Annual Progress...63764D99 BB 049 1I. ITLE (InCIu7* SOcurity Cfa.811 fcotIOn) (U) Preformulation and Formulation of Investigational New Drugs 13¶. PERSONAL AUTHORl Lach

  13. Atorvastatin calcium loaded chitosan nanoparticles: in vitro evaluation and in vivo pharmacokinetic studies in rabbits

    Directory of Open Access Journals (Sweden)

    Abdul Baquee Ahmed

    2015-06-01

    Full Text Available In this study, we prepared atorvastatin calcium (AVST loaded chitosan nanoparticles to improve the oral bioavailability of the drug. Nanoparticles were prepared by solvent evaporation technique and evaluated for its particle size, entrapment efficiency, zeta potential, in vitro release and surface morphology by scanning electron microscopy (SEM. In addition, the pharmacokinetics of AVST from the optimized formulation (FT5 was compared with marketed immediate release formulation (Atorva(r in rabbits. Particle size of prepared nanoparticles was ranged between 179.3 ± 7.12 to 256.8 ± 8.24 nm with a low polydispersity index (PI value. Zeta potential study showed that the particles are stable with positive values between 13.03 ± 0.32 to 46.90 ± 0.49 mV. FT-IR studies confirmed the absence of incompatibility of AVST with excipient used in the formulations. In vitro release study showed that the drug release was sustained for 48 h. Results of pharmacokinetics study showed significant changes in the pharmacokinetic parameter (2.2 fold increase in AUC of the optimized formulation as compared to marketed formulation (Atorva(r. Thus, the developed nanoparticles evidenced the improvement of oral bioavailability of AVST in rabbit model.

  14. Nanoparticle agglomerates in magnetoliposomes

    Science.gov (United States)

    Cintra, E. R.; Ferreira, F. S.; Santos Junior, J. L.; Campello, J. C.; Socolovsky, L. M.; Lima, E. M.; Bakuzis, A. F.

    2009-01-01

    Magnetoliposomes consist of vesicles composed of a phospholipid membrane encapsulating magnetic nanoparticles. These systems have several important applications, such as in MRI contrast agents, drug and gene carriers, and cancer treatment devices. For all of these applications, controlling the number of encapsulated magnetic nanoparticles is a key issue. In this work, we used a magneto-optical technique to obtain information about the efficiency of encapsulation, the number of nanoparticles encapsulated per liposome and also about the formation of the nanoparticle structures. The parameters studied included the effect of the duration of sonication, the presence of cholesterol in the liposome membrane, as well as time-related stability. For the liposomal vesicles prepared in this work, we found between 35 and 300 nanoparticles encapsulated per liposome, depending on the experimental conditions, consisting of small linear chains of nanoparticles, basically trimers and tetramers. The methodology developed might be useful for the investigation and improvement of the properties of several magnetic nanocarrier systems.

  15. Multifunctional nanoparticles: Analytical prospects

    International Nuclear Information System (INIS)

    Dios, Alejandro Simon de; Diaz-Garcia, Marta Elena

    2010-01-01

    Multifunctional nanoparticles are among the most exciting nanomaterials with promising applications in analytical chemistry. These applications include (bio)sensing, (bio)assays, catalysis and separations. Although most of these applications are based on the magnetic, optical and electrochemical properties of multifunctional nanoparticles, other aspects such as the synergistic effect of the functional groups and the amplification effect associated with the nanoscale dimension have also been observed. Considering not only the nature of the raw material but also the shape, there is a huge variety of nanoparticles. In this review only magnetic, quantum dots, gold nanoparticles, carbon and inorganic nanotubes as well as silica, titania and gadolinium oxide nanoparticles are addressed. This review presents a narrative summary on the use of multifuncional nanoparticles for analytical applications, along with a discussion on some critical challenges existing in the field and possible solutions that have been or are being developed to overcome these challenges.

  16. Nanoparticles and direct immunosuppression

    Science.gov (United States)

    Ngobili, Terrika A

    2016-01-01

    Targeting the immune system with nanomaterials is an intensely active area of research. Specifically, the capability to induce immunosuppression is a promising complement for drug delivery and regenerative medicine therapies. Many novel strategies for immunosuppression rely on nanoparticles as delivery vehicles for small-molecule immunosuppressive compounds. As a consequence, efforts in understanding the mechanisms in which nanoparticles directly interact with the immune system have been overshadowed. The immunological activity of nanoparticles is dependent on the physiochemical properties of the nanoparticles and its subsequent cellular internalization. As the underlying factors for these reactions are elucidated, more nanoparticles may be engineered and evaluated for inducing immunosuppression and complementing immunosuppressive drugs. This review will briefly summarize the state-of-the-art and developments in understanding how nanoparticles induce immunosuppressive responses, compare the inherent properties of nanomaterials which induce these immunological reactions, and comment on the potential for using nanomaterials to modulate and control the immune system. PMID:27229901

  17. Multifunctional nanoparticles: analytical prospects.

    Science.gov (United States)

    de Dios, Alejandro Simón; Díaz-García, Marta Elena

    2010-05-07

    Multifunctional nanoparticles are among the most exciting nanomaterials with promising applications in analytical chemistry. These applications include (bio)sensing, (bio)assays, catalysis and separations. Although most of these applications are based on the magnetic, optical and electrochemical properties of multifunctional nanoparticles, other aspects such as the synergistic effect of the functional groups and the amplification effect associated with the nanoscale dimension have also been observed. Considering not only the nature of the raw material but also the shape, there is a huge variety of nanoparticles. In this review only magnetic, quantum dots, gold nanoparticles, carbon and inorganic nanotubes as well as silica, titania and gadolinium oxide nanoparticles are addressed. This review presents a narrative summary on the use of multifunctional nanoparticles for analytical applications, along with a discussion on some critical challenges existing in the field and possible solutions that have been or are being developed to overcome these challenges. 2010 Elsevier B.V. All rights reserved.

  18. About the Sterilization of Chitosan Hydrogel Nanoparticles.

    Directory of Open Access Journals (Sweden)

    Raquel Galante

    Full Text Available In the last years, nanostructured biomaterials have raised a great interest as platforms for delivery of drugs, genes, imaging agents and for tissue engineering applications. In particular, hydrogel nanoparticles (HNP associate the distinctive features of hydrogels (high water uptake capacity, biocompatibility with the advantages of being possible to tailor its physicochemical properties at nano-scale to increase solubility, immunocompatibility and cellular uptake. In order to be safe, HNP for biomedical applications, such as injectable or ophthalmic formulations, must be sterile. Literature is very scarce with respect to sterilization effects on nanostructured systems, and even more in what concerns HNP. This work aims to evaluate the effect and effectiveness of different sterilization methods on chitosan (CS hydrogel nanoparticles. In addition to conventional methods (steam autoclave and gamma irradiation, a recent ozone-based method of sterilization was also tested. A model chitosan-tripolyphosphate (TPP hydrogel nanoparticles (CS-HNP, with a broad spectrum of possible applications was produced and sterilized in the absence and in the presence of protective sugars (glucose and mannitol. Properties like size, zeta potential, absorbance, morphology, chemical structure and cytotoxicity were evaluated. It was found that the CS-HNP degrade by autoclaving and that sugars have no protective effect. Concerning gamma irradiation, the formation of agglomerates was observed, compromising the suspension stability. However, the nanoparticles resistance increases considerably in the presence of the sugars. Ozone sterilization did not lead to significant physical adverse effects, however, slight toxicity signs were observed, contrarily to gamma irradiation where no detectable changes on cells were found. Ozonation in the presence of sugars avoided cytotoxicity. Nevertheless, some chemical alterations were observed in the nanoparticles.

  19. About the Sterilization of Chitosan Hydrogel Nanoparticles.

    Science.gov (United States)

    Galante, Raquel; Rediguieri, Carolina F; Kikuchi, Irene Satiko; Vasquez, Pablo A S; Colaço, Rogério; Serro, Ana Paula; Pinto, Terezinha J A

    2016-01-01

    In the last years, nanostructured biomaterials have raised a great interest as platforms for delivery of drugs, genes, imaging agents and for tissue engineering applications. In particular, hydrogel nanoparticles (HNP) associate the distinctive features of hydrogels (high water uptake capacity, biocompatibility) with the advantages of being possible to tailor its physicochemical properties at nano-scale to increase solubility, immunocompatibility and cellular uptake. In order to be safe, HNP for biomedical applications, such as injectable or ophthalmic formulations, must be sterile. Literature is very scarce with respect to sterilization effects on nanostructured systems, and even more in what concerns HNP. This work aims to evaluate the effect and effectiveness of different sterilization methods on chitosan (CS) hydrogel nanoparticles. In addition to conventional methods (steam autoclave and gamma irradiation), a recent ozone-based method of sterilization was also tested. A model chitosan-tripolyphosphate (TPP) hydrogel nanoparticles (CS-HNP), with a broad spectrum of possible applications was produced and sterilized in the absence and in the presence of protective sugars (glucose and mannitol). Properties like size, zeta potential, absorbance, morphology, chemical structure and cytotoxicity were evaluated. It was found that the CS-HNP degrade by autoclaving and that sugars have no protective effect. Concerning gamma irradiation, the formation of agglomerates was observed, compromising the suspension stability. However, the nanoparticles resistance increases considerably in the presence of the sugars. Ozone sterilization did not lead to significant physical adverse effects, however, slight toxicity signs were observed, contrarily to gamma irradiation where no detectable changes on cells were found. Ozonation in the presence of sugars avoided cytotoxicity. Nevertheless, some chemical alterations were observed in the nanoparticles.

  20. Characterization of progesterone loaded biodegradable blend polymeric nanoparticles

    Directory of Open Access Journals (Sweden)

    Fernanda Vitória Leimann

    2015-11-01

    Full Text Available ABSTRACT: The encapsulation of progesterone in poly (hydroxybutirate-co-hydroxyvalerate (PHBV, poly (ε-caprolactone (PCL, poly (L-lactic acid (PLLA nanoparticles and PHBV/PCL and PHBV/PLLA blend nanoparticles was investigated in this research. Nanoparticles were produced by miniemulsion/solvent evaporation technique with lecithin as surfactant and were characterized regarding to z-average diameter (Dz and polydispersity (PDI, progesterone recovery yield and encapsulation efficiency. Possible interactions between progesterone and the polymer matrices were investigated by Fourier Transform Infrared Spectroscopy (FTIR. High recoveries (up to 102.43±1.80% for the PHBV/PLLA blend and encapsulation efficiencies (up to 99.53±0.04% for PCL were achieved and the nanoparticles presented narrow size distribution (0.12±0.03 for PLLA. PCL nanoparticles (217.5±2.12nm presented significant difference with the Dz from all the other formulations (P<0.05. The most evident interaction between progesterone and the nanoparticles polymeric matrix was found to PHBV/PCL due to the increase in the intensity of the band located in 1631 cm-1.

  1. Microbial mediated preparation, characterization and optimization of gold nanoparticles.

    Science.gov (United States)

    Barabadi, Hamed; Honary, Soheila; Ebrahimi, Pouneh; Mohammadi, Milad Ali; Alizadeh, Ahad; Naghibi, Farzaneh

    2014-01-01

    The need for eco-friendly and cost effective methods for nanoparticles synthesis is developing interest in biological approaches which are free from the use of toxic chemicals as byproducts. This study aimed to biosynthesize and optimize the size of gold nanoparticles which produced by biotechnological method using Penicillium crustosum isolated from soil. Initially, Penicillium crustosum was grown in fluid czapek dox broth on shaker at 28 °C and 200 rpm for ten days and then the supernatant was separated from the mycelia to convert AuCl₄ solution into gold nanoparticles. The synthesized nanoparticles in the optimum conditions were formed with fairly well-defined dimensions and good monodispersity. The characterizations were done by using different methods (UV-Visible Spectroscopy, Fluorescence, FT-IR, AFM (Atomic Force Microscopy) and DLS (Dynamic Light Scattering). The bioconversion was optimized by Box-Behnken experimental design. The results show that the effective factors in this process were concentration of AuCl₄, pH of medium and temperature of shaker incubator. The R(2) value was calculated to be 0.9999 indicating the accuracy and ability of the polynomial model. It can be concluded that the use of multivariate analysis facilitated to find out the optimum conditions for the biosynthesis of gold nanoparticles induced by Penicillium crustosum in a time and cost effective process. The current approach suggested that rapid synthesis of gold nanoparticles would be suitable for developing a biological process for mass scale production of formulations.

  2. Hamiltonian formulation for conformal p-branes

    Energy Technology Data Exchange (ETDEWEB)

    Alvear, C.; Amorim, R.; Barcelos-Neto, J. (Inst. de Fisica, Univ. Federal do Rio de Janeiro (Brazil))

    1991-12-26

    We study the hamiltonian formulation for conformal p-branes. The difficulties which could arise from the substitution of velocities in terms of momenta, due to the nonlinearity of the theory, an circumvented. (orig.).

  3. A Hamiltonian formulation for elasticity and thermoelasticity

    CERN Document Server

    Maugin, G A

    2002-01-01

    A Hamiltonian formulation for elasticity and thermoelasticity is proposed and its relation with the corresponding configurational setting is examined. Firstly, a variational principle, concerning the 'inverse motion' mapping, is formulated and the corresponding Euler-Lagrange equations are explored. Next, this Lagrangian formulation is used to define the Hamiltonian density function. The equations of Hamilton are derived in a form which is very similar to the one of the corresponding equations in particle mechanics (finite-dimensional case). From the Hamiltonian formulation it follows that the canonical momentum is identified with the pseudomomentum. Furthermore, a meaning for the Poisson bracket is defined and the entailed relations with the canonical variables as well as the balance laws are examined.

  4. Understanding Pesticide Risks: Toxicity and Formulation

    OpenAIRE

    Muntz, Helen; Miller, Rhonda; Alston, Diane

    2016-01-01

    This fact sheet provides information about pesticide risks to human health, primary means of pesticide exposure, standardized measures of pesticide toxicity, pesticide signal words and type of pesticide formulations.

  5. Formulation and Characterization of Biodegradable Medicated ...

    African Journals Online (AJOL)

    PEG)-600, tributyl citrate, PEG-200, PEG-300, PEG-400, PEG-4000, triethyl citrate and castor oil. The gum formulations were characterized for the following parameters: texture profile analysis (TPA), biodegradation, in vitro drug release using a ...

  6. Algebraic formulation of higher gauge theory

    Science.gov (United States)

    Zucchini, Roberto

    2017-06-01

    In this paper, we present a purely algebraic formulation of higher gauge theory and gauged sigma models based on the abstract theory of graded commutative algebras and their morphisms. The formulation incorporates naturally Becchi - Rouet -Stora - Tyutin (BRST) symmetry and is also suitable for Alexandrov - Kontsevich - Schwartz-Zaboronsky (AKSZ) type constructions. It is also shown that for a full-fledged Batalin-Vilkovisky formulation including ghost degrees of freedom, higher gauge and gauged sigma model fields must be viewed as internal smooth functions on the shifted tangent bundle of a space-time manifold valued in a shifted L∞-algebroid encoding symmetry. The relationship to other formulations where the L∞-algebroid arises from a higher Lie groupoid by Lie differentiation is highlighted.

  7. Chemical-Based Formulation Design: Virtual Experimentation

    DEFF Research Database (Denmark)

    Conte, Elisa; Gani, Rafiqul

    This paper presents a software, the virtual Product-Process Design laboratory (virtual PPD-lab) and the virtual experimental scenarios for design/verification of consumer oriented liquid formulated products where the software can be used. For example, the software can be employed for the design......, the additives and/or their mixtures (formulations). Therefore, the experimental resources can focus on a few candidate product formulations to find the best product. The virtual PPD-lab allows various options for experimentations related to design and/or verification of the product. For example, the selection...... design, model adaptation). All of the above helps to perform virtual experiments by blending chemicals together and observing their predicted behaviour. The paper will highlight the application of the virtual PPD-lab in the design and/or verification of different consumer products (paint formulation...

  8. Concepts and formulations for spatial multibody dynamics

    CERN Document Server

    Flores, Paulo

    2015-01-01

    This book will be particularly useful to those interested in multibody simulation (MBS) and the formulation for the dynamics of spatial multibody systems. The main types of coordinates that can be used in the formulation of the equations of motion of constrained multibody systems are described. The multibody system, made of interconnected bodies that undergo large displacements and rotations, is fully defined. Readers will discover how Cartesian coordinates and Euler parameters are utilized and are the supporting structure for all methodologies and dynamic analysis, developed within the multibody systems methodologies. The work also covers the constraint equations associated with the basic kinematic joints, as well as those related to the constraints between two vectors. The formulation of multibody systems adopted here uses the generalized coordinates and the Newton-Euler approach to derive the equations of motion. This formulation results in the establishment of a mixed set of differential and algebraic equ...

  9. [How safe are nanoparticles?].

    Science.gov (United States)

    Lademann, J; Meinke, M; Sterry, W; Patzelt, A

    2009-04-01

    Nanoparticles are experiencing an increasing application in dermatology and cosmetics. In both application areas, the requirements of nanoparticles are in most cases widely different. As a component of sunscreens, the nanoparticles are supposed to remain on the skin surface or in the upper most layers of the stratum corneum to protect the skin against UV-radiation of the sun. Whereas, on the other hand, when particulate substances are used as carrier systems for drugs, they have to cross the skin barrier to reach the target sites within the living tissue. We discuss the perspectives and risks of the topical application of nanoparticles.

  10. Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles for oral chemotherapy of lung cancer

    Science.gov (United States)

    Jiang, Liqin; Li, Xuemin; Liu, Lingrong; Zhang, Qiqing

    2013-02-01

    Oral chemotherapy is a key step towards `chemotherapy at home', a dream of cancer patients, which will radically change the clinical practice of chemotherapy and greatly improve the quality of life of the patients. In this research, three types of nanoparticle formulation from commercial PCL and self-synthesized d-α-tocopheryl polyethylene glycol 1000 succinate (PLA-PCL-TPGS) random copolymer were prepared in this research for oral delivery of antitumor agents, including thiolated chitosan-modified PCL nanoparticles, unmodified PLA-PCL-TPGS nanoparticles, and thiolated chitosan-modified PLA-PCL-TPGS nanoparticles. Firstly, the PLA-PCL-TPGS random copolymer was synthesized and characterized. Thiolated chitosan greatly increases its mucoadhesiveness and permeation properties, thus increasing the chances of nanoparticle uptake by the gastrointestinal mucosa and improving drug absorption. The PLA-PCL-TPGS nanoparticles were found by FESEM that they are of spherical shape and around 200 nm in diameter. The surface charge of PLA-PCL-TPGS nanoparticles was reversed from anionic to cationic after thiolated chitosan modification. The thiolated chitosan-modified PLA-PCL-TPGS nanoparticles have significantly higher level of the cell uptake than that of thiolated chitosan-modified PLGA nanoparticles and unmodified PLA-PCL-TPGS nanoparticles. In vitro cell viability studies showed advantages of the thiolated chitosan-modified PLA-PCL-TPGS nanoparticles over Taxol® in terms of cytotoxicity against A549 cells. It seems that the mucoadhesive nanoparticles can increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of P-glycoprotein. In conclusion, PLA-PCL-TPGS nanoparticles modified by thiolated chitosan could enhance the cellular uptake and cytotoxicity, which revealed a potential application for oral chemotherapy of lung cancer.

  11. Advances in Nanotechnology for Efficacious and Stable Formulation Development

    Science.gov (United States)

    Putcha, Lakshimi

    2012-01-01

    Current operational medical kits aboard the International Space Station (ISS) include an array of medications intended for the treatment of minor ambulatory care symptoms, first aid, and basic life support. All medications contained in the flight kits are commercially available off-the-shelf formulations used for treatment of illnesses on Earth. However, transport and stowage of supplies including medications for space missions are exposed to adverse environmental conditions and extended shelf-life demands. Proposed missions to Mars and near-Earth objects such as asteroid 1999 AO10 will present crew health risk that is different both quantitatively and qualitatively from those encountered on ISS missions. Few drug options are available at the present time for mitigation of crew health risk of planned space exploration missions. Alternatives to standard oral formulations that include sustained and targeted delivery technologies for preventive healthcare in space will be a welcome addition to the space formulary and may include controlled release topical, sub-cutaneous, intranasal and inhalation dosage forms. An example of such a technology development endeavor can be nanotechnology-based multi-stage drug cocktail and vaccine delivery systems. Nanostructures also have the ability to protect drugs encapsulated within them from physiologic degradation, target their delivery with sustained release and are suitable for per oral routes of administration. The use of nanostructures such as polymeric nanoparticles offers a non-invasive approach for penetrating the blood brain barrier. Finally, nanotechnology offers great potential for the development of safe and efficacious drug delivery systems for preventive health care in space and on Earth.

  12. The Boltzmann equation in the difference formulation

    Energy Technology Data Exchange (ETDEWEB)

    Szoke, Abraham [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Brooks III, Eugene D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-05-06

    First we recall the assumptions that are needed for the validity of the Boltzmann equation and for the validity of the compressible Euler equations. We then present the difference formulation of these equations and make a connection with the time-honored Chapman - Enskog expansion. We discuss the hydrodynamic limit and calculate the thermal conductivity of a monatomic gas, using a simplified approximation for the collision term. Our formulation is more consistent and simpler than the traditional derivation.

  13. Preformulation and Formulation Investigational New Drugs

    Science.gov (United States)

    1990-07-01

    AD-A252 024 CONTRACT NO: DAMD17-85-C-5003 TITLE: PREFORMULATION AND FORMULATION INVESTIGATIONAL NEW DRUGS PRINCIPAL INVESTIGATOR: Douglas R. Flanagan... PREFORMULATION AND FOMULATION INVESTIGATIONAL Contract No. NEW DRUGS DAMD17-85-C-5003 6. AUTHOR(S) 0603807A Douglas R. Flanagan, John L. Lach (deceased), and...RA V, 16. PRICE CODE formulation studies , clinical studies 17. SECURITY CLASSIFICATION 18. SECURITY CtASSIFICATION 19. SECURITY CLASSIFICATION 20

  14. Note on the ideal frame formulation

    Science.gov (United States)

    Lara, Martin

    2017-09-01

    An implementation of the ideal frame formulation of perturbed Keplerian motion is presented which only requires the integration of a differential system of dimension 7, contrary to the 8 variables traditionally integrated with this approach. The new formulation is based on the integration of a scaled version of the Eulerian set of redundant parameters and slightly improves runtime performance with respect to the 8-dimensional case while retaining comparable accuracy.

  15. Triggering of RNA interference with RNA-RNA, RNA-DNA, and DNA-RNA nanoparticles.

    Science.gov (United States)

    Afonin, Kirill A; Viard, Mathias; Kagiampakis, Ioannis; Case, Christopher L; Dobrovolskaia, Marina A; Hofmann, Jen; Vrzak, Ashlee; Kireeva, Maria; Kasprzak, Wojciech K; KewalRamani, Vineet N; Shapiro, Bruce A

    2015-01-27

    Control over cellular delivery of different functionalities and their synchronized activation is a challenging task. We report several RNA and RNA/DNA-based nanoparticles designed to conditionally activate the RNA interference in various human cells. These nanoparticles allow precise control over their formulation, stability in blood serum, and activation of multiple functionalities. Importantly, interferon and pro-inflammatory cytokine activation assays indicate the significantly lower responses for DNA nanoparticles compared to the RNA counterparts, suggesting greater potential of these molecules for therapeutic use.

  16. Triggering of RNA Interference with RNA–RNA, RNA–DNA, and DNA–RNA Nanoparticles

    Science.gov (United States)

    2015-01-01

    Control over cellular delivery of different functionalities and their synchronized activation is a challenging task. We report several RNA and RNA/DNA-based nanoparticles designed to conditionally activate the RNA interference in various human cells. These nanoparticles allow precise control over their formulation, stability in blood serum, and activation of multiple functionalities. Importantly, interferon and pro-inflammatory cytokine activation assays indicate the significantly lower responses for DNA nanoparticles compared to the RNA counterparts, suggesting greater potential of these molecules for therapeutic use. PMID:25521794

  17. An herbal formulation for hemorrhoids treatment

    Directory of Open Access Journals (Sweden)

    S. Dehdari

    2017-11-01

    Full Text Available Background and objectives: Hemorrhoids is the most painful rectal disease. Straining and pregnancy seem playing chief roles in the development of hemorrhoids. Symptoms of hemorrhoids may include bleeding, inflammation and pain. Despite current medical efforts, many discomforts of hemorrhoids have not been handled. The aim of the present study was to formulate and evaluate Itrifal-e muqil (IM tablet to achieve desired pharmaceutical properties. Method: Quality control tests of Allium ampeloperasum L, Commiphora mukul (Hook. ex Stocks Engl., Phyllanthus emblica L., Terminalia chebula Retz. and Terminalia bellerica Retz. were performed. Afterwards, different formulations were prepared and their physical properties were evaluated. Subsequently, the formulation was coated and its physicochemical characteristics were assessed. Result: All of the herbs demonstrated good results in quality control tests according to United State Pharmacopeia (USP. Formulation-1 that was completely prepared based on explained manufacturing process of IM in traditional medicine manuscripts did not show suitable pharmaceutical properties. Among different formulations, Formulation-3 that consisted of A. ampeloperasum, C. mukul, P. emblica, T. chebula and T. bellerica, displayed best outcomes through different tests. Conclusion: Modern pharmaceutical approaches can excellently be adapted for IM preparations.

  18. Microbiological quality of pediatric oral liquid formulations

    Directory of Open Access Journals (Sweden)

    Maria Josep Cabañas Poy

    2016-09-01

    Full Text Available The oral administration of drugs to the pediatric population involves the extemporaneous preparation of liquid formulations. These formulations have studies on their physicochemical stability, but they often lack microbiological studies. The objective of this study is to check the microbiological quality of five oral liquid formulations prepared with different excipients, which represent five major combinations, in two conditions: kept unopened until the day of the test, and in a multi-dose vial opened daily. The formulations were prepared according to standard operating procedures. Half of each batch was packaged in vials that remained closed until the day of testing, and the other half in a single container which was opened daily. Both the vials and the containers had been previously sterilized. Microbiological tests were performed weekly during the first month of the study, and then every two weeks, until the expiration date. The microbiological quality of oral liquid formulations is determined by the Royal Spanish Pharmacopoeia. The conclusion was that none of the formulations prepared that were packaged in sterilized containers became contaminated, either in unopened vials or in multi-dose containers when they were opened daily

  19. The coevent formulation of quantum theory

    International Nuclear Information System (INIS)

    Wallden, Petros

    2013-01-01

    Understanding quantum theory has been a subject of debate from its birth. Many different formulations and interpretations have been proposed. Here we examine a recent novel formulation, namely the coevents formulation. It is a histories formulation and has as starting point the Feynman path integral and the decoherence functional. The new ontology turns out to be that of a coarse-grained history. We start with a quantum measure defined on the space of histories, and the existence of zero covers rules out single-history as potential reality (the Kochen Specker theorem casted in histories form is a special case of a zero cover). We see that allowing coarse-grained histories as potential realities avoids the previous paradoxes, maintains deductive non-contextual logic (alas non-Boolean) and gives rise to a unique classical domain. Moreover, we can recover the probabilistic predictions of quantum theory with the use of the Cournot's principle. This formulation, being both a realist formulation and based on histories, is well suited conceptually for the purposes of quantum gravity and cosmology.

  20. Solid lipid nanoparticles with and without hydroxypropyl-β-cyclodextrin: a comparative study of nanoparticles designed for colonic drug delivery

    Science.gov (United States)

    Spada, Gianpiera; Gavini, Elisabetta; Cossu, Massimo; Rassu, Giovanna; Giunchedi, Paolo

    2012-03-01

    New solid lipid nanoparticles (SLN), composed of Compritol ATO888 (C) and hydroxypropyl-β-cyclodextrin (HP), were developed in order to study a new colon-specific formulation for diclofenac sodium (D) delivery. The prepared batches differ from each other by the molecular ratio between HP and D and by the composition of the matrix. Nanoparticles composed of an exclusively lipid matrix and nanoparticles with an oligomeric and lipid matrix were compared in order to establish the effect of both components on the drug delivery tests performed. The SLN preparation method was based on the oil/water hot homogenization process. Emulsions produced were cooled at room temperature and lyophilized in order to obtain dried nanoparticles; possible damage to nanoparticle shape and size was avoided by the addition of cryoprotectants to the aqueous dispersion of nanoparticles before exsiccation. An in vitro toxicity study was performed using CaCo2 cells to establish the safety of the prepared SLN. Data obtained showed that production method studied guarantees emulsions composed of nanosized drops which can be dried by lyophilization into SLN with a size range of 300-600 nm. In vitro and ex vivo tests demonstrated that dried SLN can be considered as colon delivery systems; however, the matrix composition as well as the presence of cryoprotectant on their surface influences the release and permeation rate of D. The in vitro toxicity studies indicated that the SLN are well tolerated.

  1. Solid lipid nanoparticles with and without hydroxypropyl-β-cyclodextrin: a comparative study of nanoparticles designed for colonic drug delivery

    International Nuclear Information System (INIS)

    Spada, Gianpiera; Gavini, Elisabetta; Cossu, Massimo; Rassu, Giovanna; Giunchedi, Paolo

    2012-01-01

    New solid lipid nanoparticles (SLN), composed of Compritol ATO888 (C) and hydroxypropyl-β-cyclodextrin (HP), were developed in order to study a new colon-specific formulation for diclofenac sodium (D) delivery. The prepared batches differ from each other by the molecular ratio between HP and D and by the composition of the matrix. Nanoparticles composed of an exclusively lipid matrix and nanoparticles with an oligomeric and lipid matrix were compared in order to establish the effect of both components on the drug delivery tests performed. The SLN preparation method was based on the oil/water hot homogenization process. Emulsions produced were cooled at room temperature and lyophilized in order to obtain dried nanoparticles; possible damage to nanoparticle shape and size was avoided by the addition of cryoprotectants to the aqueous dispersion of nanoparticles before exsiccation. An in vitro toxicity study was performed using CaCo 2 cells to establish the safety of the prepared SLN. Data obtained showed that production method studied guarantees emulsions composed of nanosized drops which can be dried by lyophilization into SLN with a size range of 300–600 nm. In vitro and ex vivo tests demonstrated that dried SLN can be considered as colon delivery systems; however, the matrix composition as well as the presence of cryoprotectant on their surface influences the release and permeation rate of D. The in vitro toxicity studies indicated that the SLN are well tolerated. (paper)

  2. Organically Modified Silica Nanoparticles Interaction with Macrophage Cells: Assessment of Cell Viability on the Basis of Physicochemical Properties.

    Science.gov (United States)

    Kumar, Dhiraj; Mutreja, Isha; Keshvan, Prashant C; Bhat, Madhusudan; Dinda, Amit K; Mitra, Susmita

    2015-11-01

    Silica nanoparticles have drawn a lot of attention for nanomedicine application, and this is attributed to their biocompatibility and ease of surface functionalization. However, successful utilization of these inorganic systems for biomedical application depends on their physicochemical properties. This study, therefore, discusses in vitro toxicity of organically modified silica nanoparticles on the basis of size, shape, and surface properties of silica nanoparticles. Spherical- and oval-shaped nanoparticles having hydroxyl and amine groups were synthesized in Tween 80 micelles using different organosilanes. Nanoparticles of similar size and morphology were considered for comparative assessment. "As-prepared" nanoparticles were characterized in terms of size, shape, and surface properties using ZetaSizer, transmission electron microscopy, and Fourier transform infrared to establish the above parameters. In vitro analysis in terms of nanoparticle-based toxicity was performed on J-774 (macrophage) cell line using propidium iodide-4',6-diamidino-2-phenylindol and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Fluorescent dye-entrapped nanoparticles were used to visualize the uptake of the nanoparticles by macrophage cells. Results from cell studies suggested low levels of toxicity for different nanoparticle formulations studied, therefore are suitable for nanocarrier application for poorly soluble molecules. On the contrary, the nanoparticles of similar size and shape, having amine groups and low net negative charge, do not exhibit any in vitro cytotoxicity. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  3. In vitro, in vivo and pharmacokinetic assessment of amikacin sulphate laden polymeric nanoparticles meant for controlled ocular drug delivery

    Science.gov (United States)

    Sharma, Upendra Kumar; Verma, Amita; Prajapati, Sunil Kuamr; Pandey, Himanshu; Pandey, Avinash C.

    2015-02-01

    The rationale of current exploration was to formulate positively charged amikacin-loaded polymeric nanoparticles providing a controlled release attribute. Amikacin sulphate-loaded nanoparticles were prepared by w/o/w emulsification solvent evaporation approach succeeded by high-pressure homogenization. Two bioadhesive positively charged polymers, Eudragit® RS 100 and Eudragit® RL 100, were used in the blend, with variable ratios of drug and polymer. The formulations were assessed in terms of particle size and zeta potential. Thermal gravimetric analysis was brought out on the samples of drug, polymer and drug polymer complex. Drug loading and release attributes of the nanoparticles were scrutinized and antimicrobial activity in contrast to Staphylococcus aureus was appraised. Ocular irritation test, in vivo ocular retention study, in vivo release profile (permeation study) and in vivo antibacterial activity of polymeric nanosuspensions were executed. No rupture consequence but a lengthened drug release was contemplated from all formulations. Amikacin sulphate release from the polymeric nanoparticles reflected a better fit with Korsmeyer-Peppas model. In the course of the antibacterial activity of nanoparticles against S. aureus, formulation AE1 displays the most prominent inhibitory effect as compared with marketed formulation of amikacin sulphate.

  4. Interaction of lipid nanoparticles with human epidermis and an organotypic cell culture model

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Bunjes, Heike; Fahr, Alfred

    2008-01-01

    Various lipid nanoparticle formulations were investigated with respect to (trans)dermal drug delivery with special regard to the mechanism of their effects on human and an organotypic cell culture epidermis. Potential alterations of stratum corneum lipid domains were studied using fluorescence...... assays with labeled liposomes and thermal analysis of isolated stratum corneum. Influences on the permeation of corticosterone were investigated and the occlusive properties of the nanoparticles were determined by measurements of the transepidermal water loss (TEWL). The penetration of a fluorescence dye...... was visualized by fluorescence microscopy of cross sections of human epidermis after incubation with cubic and solid lipid nanoparticles. Corticosterone permeation was limited when applied in matrix-type lipid nanoparticles (fat emulsion, smectic and solid lipid nanoparticles). An adhesion of solid lipid...

  5. Rheology and stability kinetics of bare silicon nanoparticle inks for low-cost direct printing

    International Nuclear Information System (INIS)

    More, Priyesh V.; Jeong, Sunho; Seo, Yeong-Hui; Ryu, Beyong-Hwan; Choi, Youngmin; Kim, Seong Jip; Nahm, Sahn

    2013-01-01

    Highly dispersed and stable silicon nanoparticles ink is formulated for its application in direct printing or printable electronics. These dispersions are prepared from free-standing silicon nanoparticles which are not capped with any organic ligand, making it suitable for electronic applications. Silicon nanoparticles dispersions are prepared by suspending the nanoparticles in benzonitrile or ethanol by using polypropylene glycol (PPG) as a binder. All the samples show typical shear thinning behavior while the dispersion samples show low viscosities signifying good quality dispersion. Such thinning behavior favors in fabrication of dense films with spin-coating or patterns with drop casting. The dispersion stability is monitored by turbiscan measurements showing good stability for one week. A low-cost direct printing method for dispersion samples is also demonstrated to obtain micro-sized patterns. Low electrical resistivity of resulting patterns, adjustable viscosity and good stability makes these silicon nanoparticles dispersions highly applicable for direct printing process

  6. Plumbagin Nanoparticles Induce Dose and pH Dependent Toxicity on Prostate Cancer Cells.

    Science.gov (United States)

    Nair, Harikrishnan A; Snima, K S; Kamath, Ravindranath C; Nair, Shantikumar V; Lakshmanan, Vinoth-Kumar

    2015-01-01

    Stable nano-formulation of Plumbagin nanoparticles from Plumbago zeylanica root extract was explored as a potential natural drug against prostate cancer. Size and morphology analysis by DLS, SEM and AFM revealed the average size of nanoparticles prepared was 100±50nm. In vitro cytotoxicity showed concentration and time dependent toxicity on prostate cancer cells. However, plumbagin crude extract found to be highly toxic to normal cells when compared to plumbagin nanoformulation, thus confirming nano plumbagin cytocompatibility with normal cells and dose dependent toxicity to prostate cells. In vitro hemolysis assay confirmed the blood biocompatibility of the plumbagin nanoparticles. In wound healing assay, plumbagin nanoparticles provided clues that it might play an important role in the anti-migration of prostate cancer cells. DNA fragmentation revealed that partial apoptosis induction by plumbagin nanoparticles could be expected as a potent anti-cancer effect towards prostate cancer.

  7. Antimicrobial efficacy and ocular cell toxicity from silver nanoparticles

    OpenAIRE

    Santoro, Colleen M.; Duchsherer, Nicole L.; Grainger, David W.

    2007-01-01

    Silver in various forms has long been recognized for antimicrobial properties, both in biomedical devices and in eyes. However, soluble drugs used on the ocular surface are rapidly cleared through tear ducts and eventually ingested, resulting in decreased efficacy of the drug on its target tissue and potential concern for systemic side effects. Silver nanoparticles were studied as a source of anti-microbial silver for possible controlled-release contact lens controlled delivery formulations. ...

  8. Noninvasive detection of nanoparticle clustering by water proton NMR

    Energy Technology Data Exchange (ETDEWEB)

    Taraban, Marc B.; Truong, Huy C.; Ilavsky, Jan; DePaz, Roberto A.; Lobo, Brian; Yu, Y. Bruce

    2017-06-01

    It is shown that water proton NMR can detect uncontrolled clustering of inert nanoparticles (NPs) formulated as aqueous suspensions. The clustering of NPs causes the compartmentalization of water molecules, leading to accelerated proton spin de-coherence, and hence, much faster water transverse relaxation rates. The results suggest that water proton NMR can be used to noninvasively inspect NP products by commercial end users and researchers.

  9. PEGylated versus non-PEGylated magnetic nanoparticles as camptothecin delivery system

    Directory of Open Access Journals (Sweden)

    Paula M. Castillo

    2014-08-01

    Full Text Available Camptothecin (CPT; (S-(+-4-ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-(4H,12H-dione is a highly cytotoxic natural alkaloid that has not yet found use as chemotherapeutic agent due to its poor water-solubility and chemical instability and, as a consequence, no effective administration means have been designed. In this work, camptothecin has been successfully loaded into iron oxide superparamagnetic nanoparticles with an average size of 14 nm. It was found that surface modification of the nanoparticles by polyethylene glycol enables loading a large amount of camptothecin. While the unloaded nanoparticles do not induce apoptosis in the H460 lung cancer cell line, the camptothecin-loaded nanoparticle formulations exhibit remarkable pro-apoptotic activity. These results indicate that camptothecin retains its biological activity after loading onto the magnetic nanoparticles. The proposed materials represent novel materials based on naturally occurring bioactive molecules loaded onto nanoparticles to be used as chemotherapeutic formulations. The procedure seems apt to be extended to other active molecules extracted from natural products. In addition, these materials offer the potential of being further implemented for combined imaging and therapeutics, as magnetic nanoparticles are known to be multifunctional tools for biomedicine.

  10. Controlling and Predicting Nanoparticle Formation by Block Copolymer Directed Rapid Precipitations.

    Science.gov (United States)

    Pagels, Robert F; Edelstein, Jasmine; Tang, Christina; Prud'homme, Robert K

    2018-02-14

    Nanoparticles have shown promise in several biomedical applications, including drug delivery and medical imaging; however, quantitative prediction of nanoparticle formation processes that scale from laboratory to commercial production has been lacking. Flash NanoPrecipitation (FNP) is a scalable technique to form highly loaded, block copolymer protected nanoparticles. Here, the FNP process is shown to strictly obey diffusion-limited aggregation assembly kinetics, and the parameters that control the nanoparticle size and the polymer brush density on the nanoparticle surface are shown. The particle size, ranging from 40 to 200 nm, is insensitive to the molecular weight and chemical composition of the hydrophobic encapsulated material, which is shown to be a consequence of the diffusion-limited growth kinetics. In a simple model derived from these kinetics, a single constant describes the 46 unique nanoparticle formulations produced here. The polymer brush densities on the nanoparticle surface are weakly dependent on the process parameters and are among the densest reported in the literature. Though modest differences in brush densities are observed, there is no measurable difference in the amount of protein adsorbed within this range. This work highlights the material-independent and universal nature of the Flash NanoPrecipitation process, allowing for the rapid translation of formulations to different stabilizing polymers and therapeutic loads.

  11. A Novel Polyacrylamide Magnetic Nanoparticle Contrast Agent for Molecular Imaging using MRI

    Directory of Open Access Journals (Sweden)

    Bradford A. Moffat

    2003-10-01

    Full Text Available A novel Polyacrylamide superparamagnetic iron oxide nanoparticle platform is described which has been synthetically prepared such that multiple crystals of iron oxide are encapsulated within a single Polyacrylamide matrix (PolyAcrylamide Magnetic [PAM] nanoparticles. This formulation provides for an extremely large T2 and T2* relaxivity of between 620 and 1140 sec−1 mM−1. Administration of PAM nanoparticles into rats bearing orthotopic 9L gliomas allowed quantitative pharmacokinetic analysis of the uptake of nanoparticles in the vasculature, brain, and glioma. Addition of polyethylene glycol of varying sizes (0.6, 2, and 10 kDa to the surface of the PAM nanoparticles resulted in an increase in plasma half-life and affected tumor uptake and retention of the nanoparticles as quantified by changes in tissue contrast using MRI. The flexible formulation of these nanoparticles suggests that future modifications could be accomplished allowing for their use as a targeted molecular imaging contrast agent and/or therapeutic platform for multiple indications.

  12. Optimization of Preparation Techniques for Poly(Lactic Acid-Co-Glycolic Acid) Nanoparticles

    International Nuclear Information System (INIS)

    Birnbaum, Duane T.; Kosmala, Jacqueline D.; Brannon-Peppas, Lisa

    2000-01-01

    Microparticles and nanoparticles of poly(lactic acid-co-glycolic acid) (PLAGA) are excellent candidates for the controlled release of many pharmaceutical compounds because of their biodegradable nature. The preparation of submicron PLAGA particles poses serious challenges that are not necessarily present when preparing microparticles. We have evaluated several combinations of organic solvents and surfactants used in the formulation of PLAGA nanoparticles. Critical factors such as the ability to separate the nanoparticles from the surfactant, the ability to re-suspend the nanoparticles after freeze-drying, formulation yield and nanoparticle size were studied. The smallest particles were obtained using the surfactant/solvent combination of sodium dodecyl sulfate and ethyl acetate (65 nm) and the largest particles were obtained using poly(vinyl alcohol) and dichloromethane (466 nm). However, the optimal nanoparticles were produced using either acetone or ethyl acetate as the organic solvent and poly(vinyl alcohol) or human serum albumin as the surfactant. This is because the most critical measure of performance of these nanoparticles proved to be their ability to re-suspend after freeze-drying

  13. Nanoparticles as safe and effective delivery systems of antifungal agents: Achievements and challenges.

    Science.gov (United States)

    Soliman, Ghareb M

    2017-05-15

    Invasive fungal infections are becoming a major health concern in several groups of patients leading to severe morbidity and mortality. Moreover, cutaneous fungal infections are a major cause of visits to outpatient dermatology clinics. Despite the availability of several effective agents in the antifungal drug arena, their therapeutic outcome is less than optimal due to limitations related to drug physicochemical properties and toxicity. For instance, poor aqueous solubility limits the formulation options and efficacy of several azole antifungal drugs while toxicity limits the benefits of many other drugs. Nanoparticles hold great promise to overcome these limitations due to their ability to enhance drug aqueous solubility, bioavailability and antifungal efficacy. Further, drug incorporation into nanoparticles could greatly reduce its toxicity. Despite these interesting nanoparticle features, there are only few marketed nanoparticle-based antifungal drug formulations. This review sheds light on different classes of nanoparticles used in antifungal drug delivery, such as lipid-based vesicles, polymeric micelles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and dendrimers with emphasis on their advantages and limitations. Translation of these nanoformulations from the lab to the clinic could be facilitated by focusing the research on overcoming problems related to nanoparticle stability, drug loading and high cost of production and standardization. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Encapsulation of antigen-loaded silica nanoparticles into microparticles for intradermal powder injection.

    Science.gov (United States)

    Deng, Yibin; Mathaes, Roman; Winter, Gerhard; Engert, Julia

    2014-10-15

    Epidermal powder immunisation (EPI) is being investigated as a promising needle-free delivery methods for vaccination. The objective of this work was to prepare a nanoparticles-in-microparticles (nano-in-micro) system, integrating the advantages of nanoparticles and microparticles into one vaccine delivery system for epidermal powder immunisation. Cationic mesoporous silica nanoparticles (MSNP-NH2) were prepared and loaded with ovalbumin as a model antigen. Loading was driven by electrostatic interactions. Ovalbumin-loaded silica nanoparticles were subsequently formulated into sugar-based microparticles by spray-freeze-drying. The obtained microparticles meet the size requirement for EPI. Confocal microscopy was used to demonstrate that the nanoparticles are homogeneously distributed in the microparticles. Furthermore, the silica nanoparticles in the dry microparticles can be re-dispersed in aqueous solution showing no aggregation. The recovered ovalbumin shows integrity compared to native ovalbumin. The present nano-in-micro system allows (1) nanoparticles to be immobilized and finely distributed in microparticles, (2) microparticle formation and (3) re-dispersion of nanoparticles without subsequent aggregation. The nanoparticles inside microparticles can (1) adsorb proteins to cationic shell/surface voids in spray-dried products without detriment to ovalbumin stability, (2) deliver antigens in nano-sized modes to allow recognition by the immune system. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Development of lapachol topical formulation: anti-inflammatory study of a selected formulation.

    Science.gov (United States)

    Lira, Ana Amélia M; Sester, Elizângela A; Carvalho, André Luis M; Strattmann, Ruth R; Albuquerque, Miracy M; Wanderley, Almir G; Santana, Davi P

    2008-01-01

    This study aimed at developing a topical formulation of lapachol, a compound isolated from various Bignoniaceae species and at evaluating its topical anti-inflammatory activity. The influence of the pharmaceutical form and different types of emulsifiers was evaluated by in-vitro release studies. The formulations showing the highest release rate were selected and assessed trough skin permeation and retention experiments. It was observed that the gel formulation provided significantly higher permeation and retained amount (3.9-fold) of lapachol as compared to the gel-cream formulation. Antinociceptive and antiedematogenic activities of the most promising formulation were also evaluated. Lapachol gel reduced the increase in hind-paw volume induced by carrageenan injection and reduced nociception produced by acetic acid (0.8% in water, i.p.) when used topically. These results suggest that topical delivery of lapachol from gel formulations may be an effective medication for both dermal and subdermal injuries.

  16. Target Nanoparticles for Therapy - SANS and DLS of Drug Carrier Liposomes and Polymer Nanoparticles

    Science.gov (United States)

    Nawroth, T.; Johnson, R.; Krebs, L.; Khoshakhlagh, P.; Langguth, P.; Hellmann, N.; Goerigk, G.; Boesecke, P.; Bravin, A.; Le Duc, G.; Szekely, N.; Schweins, R.

    2016-09-01

    T arget Nano-Pharmaceutics shall improve therapy and diagnosis of severe diseases, e.g. cancer, by individual targeting of drug-loaded nano-pharmaceuticals towards cancer cells, and drug uptake receptors in other diseases. Specific ligands, proteins or cofactors, which are recognized by the diseased cells or cells of food and drug uptake, are bound to the nanoparticle surface, and thus capable of directing the drug carriers. The strategy has two branches: a) for parenteral cancer medicine a ligand set (2-5 different, surface-linked) are selected according to the biopsy analysis of the patient tissue e.g. from tumor.; b) in the oral drug delivery part the drug transport is enforced by excipients/ detergents in combination with targeting materials for cellular receptors resulting in an induced drug uptake. Both targeting nanomaterials are characterized by a combination of SANS + DLS and SAXS or ASAXS in a feedback process during development by synthesis, nanoparticle assembly and formulation.

  17. Target Nanoparticles for Therapy - SANS and DLS of Drug Carrier Liposomes and Polymer Nanoparticles

    International Nuclear Information System (INIS)

    Nawroth, T; Johnson, R; Krebs, L; Khoshakhlagh, P; Langguth, P; Hellmann, N; Goerigk, G; Boesecke, P; Bravin, A; Duc, G Le; Szekely, N; Schweins, R

    2016-01-01

    T arget Nano-Pharmaceutics shall improve therapy and diagnosis of severe diseases, e.g. cancer, by individual targeting of drug-loaded nano-pharmaceuticals towards cancer cells, and drug uptake receptors in other diseases. Specific ligands, proteins or cofactors, which are recognized by the diseased cells or cells of food and drug uptake, are bound to the nanoparticle surface, and thus capable of directing the drug carriers. The strategy has two branches: a) for parenteral cancer medicine a ligand set (2-5 different, surface-linked) are selected according to the biopsy analysis of the patient tissue e.g. from tumor.; b) in the oral drug delivery part the drug transport is enforced by excipients/ detergents in combination with targeting materials for cellular receptors resulting in an induced drug uptake. Both targeting nanomaterials are characterized by a combination of SANS + DLS and SAXS or ASAXS in a feedback process during development by synthesis, nanoparticle assembly and formulation. (paper)

  18. Formation of spherical protein nanoparticles without impacting protein integrity

    International Nuclear Information System (INIS)

    Montalvo, Brenda L; Pacheco, Yamaris; Sosa, Brian A; Velez, Denisse; Sanchez, Giselle; Griebenow, Kai

    2008-01-01

    Protein formulation at the nanoscale is challenging because of protein susceptibility to chemical and physical degradation during processing. Herein, we present a straightforward method to prepare spherical protein nanoparticles by co-lyophilizing five structurally different enzymes (horseradish peroxidase, carbonic anhydrase, lysozyme, subtilisin Carlsberg and α-chymotrypsin) with methyl-β-cyclodextrin followed by suspension of the powders in ethyl acetate. The size distribution was narrow and varied from 88 ± 14 to 148 ± 16 nm as determined by dynamic light scattering. Scanning and transmission electron micrographs confirmed the size and spherical morphology of the protein nanoparticles. Residual activities for all enzymes tested were 100% upon dissolving the nanoparticles in buffer and no insoluble aggregates were formed.

  19. Lipid nanoparticles for administration of poorly water soluble neuroactive drugs.

    Science.gov (United States)

    Esposito, Elisabetta; Drechsler, Markus; Mariani, Paolo; Carducci, Federica; Servadio, Michela; Melancia, Francesca; Ratano, Patrizia; Campolongo, Patrizia; Trezza, Viviana; Cortesi, Rita; Nastruzzi, Claudio

    2017-09-01

    This study describes the potential of solid lipid nanoparticles and nanostructured lipid carriers as nano-formulations to administer to the central nervous system poorly water soluble drugs. Different neuroactive drugs, i.e. dimethylfumarate, retinyl palmitate, progesterone and the endocannabinoid hydrolysis inhibitor URB597 have been studied. Lipid nanoparticles constituted of tristearin or tristearin in association with gliceryl monoolein were produced. The nanoencapsulation strategy allowed to obtain biocompatible and non-toxic vehicles, able to increase the solubility of the considered neuroactive drugs. To improve URB597 targeting to the brain, stealth nanoparticles were produced modifying the SLN surface with polysorbate 80. A behavioural study was conducted in rats to test the ability of SLN containing URB597 given by intranasal administration to alter behaviours relevant to psychiatric disorders. URB597 maintained its activity after nanoencapsulation, suggesting the possibility to propose this kind of vehicle as alternative to unphysiological mixtures usually employed for animal and clinical studies.

  20. Cell Membrane-Cloaked Nanoparticles for Targeted Therapeutics

    Science.gov (United States)

    Luk, Brian Tsengchi

    The advent of nanoparticle-based delivery systems has made a significant impact on clinical patient outcomes. In recent decades, myriad nanoparticle-based therapeutic agents have been developed for the treatment and management of ailments such as cancer, diabetes, pain, bacterial infections, and asthma, among many others. Nanotherapeutics offer many distinct advantages over conventional free drug formulations. For example, nanoparticles are able to accumulate at tumor sites by extravasation through leaky vasculature at tumor sites via the enhanced permeability and retention (EPR) effect; nanoparticles can also be tailored to have desirable characteristics, such as prolonged circulation in the blood stream, improved drug encapsulation, and sustained or triggered drug release. Currently, a growing number of nanoformulations with favorable pharmacological profiles and promising efficacy are being used in clinical trials for the treatment of various cancers. Building on the success of these encouraging clinical results, new engineering strategies have emerged that combine synthetic nanoparticles with natural biomaterials to create nature-inspired biomimetic delivery systems. The work presented in this dissertation focuses on the biointerfacing between synthetic and natural materials, namely in the manifestation of cell membrane-coated nanoparticles. By exploiting the natural functionalities of source cell membranes, cell membrane-cloaked nanoparticles have huge potential in the delivery of therapeutic agents for a variety of applications. The first portion of this thesis will focus on understanding the fundamentals underlying cell membrane coating on synthetic nanoparticles. First introduced in 2011, cell membrane-cloaked nanoparticles showed immediate promise in drug delivery applications, but further understanding was necessary to be able to harness the full potential of the membrane coating platform. The first section provides further insight into the interfacial

  1. Encapsulation of gold nanoparticles into self-assembling protein nanoparticles

    OpenAIRE

    Yang Yongkun; Burkhard Peter

    2012-01-01

    Abstract Background Gold nanoparticles are useful tools for biological applications due to their attractive physical and chemical properties. Their applications can be further expanded when they are functionalized with biological molecules. The biological molecules not only provide the interfaces for interactions between nanoparticles and biological environment, but also contribute their biological functions to the nanoparticles. Therefore, we used self-assembling protein nanoparticles (SAPNs...

  2. Silica Coating of Nonsilicate Nanoparticles for Resin-Based Composite Materials.

    Science.gov (United States)

    Kaizer, M R; Almeida, J R; Gonçalves, A P R; Zhang, Y; Cava, S S; Moraes, R R

    2016-11-01

    This study was designed to develop and characterize a silica-coating method for crystalline nonsilicate ceramic nanoparticles (Al 2 O 3 , TiO 2 , and ZrO 2 ). The hypothesis was that the coated nonsilicate nanoparticles would stably reinforce a polymeric matrix due to effective silanation. Silica coating was applied via a sol-gel method, with tetraethyl orthosilicate as a silica precursor, followed by heat treatment. The chemical and microstructural characteristics of the nanopowders were evaluated before and after silica coating through x-ray diffraction, BET (Brunauer-Emmett-Teller), energy-dispersive x-ray spectroscopy, field emission scanning electron microscopy, and transmission electron microscopy analyses. Coated and noncoated nanoparticles were silanated before preparation of hybrid composites, which contained glass microparticles in addition to the nanoparticles. The composites were mechanically tested in 4-point bending mode after aging (10,000 thermal cycles). Results of all chemical and microstructural analyses confirmed the successful obtaining of silica-coated nanoparticles. Two distinct aspects were observed depending on the type of nanoparticle tested: 1) formation of a silica shell on the surface of the particles and 2) nanoparticle clusters embedded into a silica matrix. The aged hybrid composites formulated with the coated nanoparticles showed improved flexural strength (10% to 30% higher) and work of fracture (35% to 40% higher) as compared with composites formulated with noncoated nanoparticles. The tested hypothesis was confirmed: silanated silica-coated nonsilicate nanoparticles yielded stable reinforcement of dimethacrylate polymeric matrix due to effective silanation. The silica-coating method presented here is a versatile and promising novel strategy for the use of crystalline nonsilicate ceramics as a reinforcing phase of polymeric composite biomaterials.

  3. Rationally designed oxaliplatin-nanoparticle for enhanced antitumor efficacy

    International Nuclear Information System (INIS)

    Paraskar, Abhimanyu; Soni, Shivani; Roy, Bhaskar; Papa, Anne-Laure; Sengupta, Shiladitya

    2012-01-01

    Nanoscale drug delivery vehicles have been extensively studied as carriers for cancer chemotherapeutics. However, the formulation of platinum chemotherapeutics in nanoparticles has been a challenge arising from their physicochemical properties. There are only a few reports describing oxaliplatin nanoparticles. In this study, we derivatized the monomeric units of a polyisobutylene maleic acid copolymer with glucosamine, which chelates trans-1,2-diaminocyclohexane (DACH) platinum (II) through a novel monocarboxylato and O → Pt coordination linkage. At a specific polymer to platinum ratio, the complex self-assembled into a nanoparticle, where the polymeric units act as the leaving group, releasing DACH–platinum in a sustained pH-dependent manner. Sizing was done using dynamic light scatter and electron microscopy. The nanoparticles were evaluated for efficacy in vitro and in vivo. Biodistribution was quantified using inductively coupled plasma atomic absorption spectroscopy (ICP-AAS). The PIMA–GA–DACH–platinum nanoparticle was found to be more active than free oxaliplatin in vitro. In vivo, the nanoparticles resulted in greater tumor inhibition than oxaliplatin (equivalent to 5 mg kg −1 platinum dose) with minimal nephrotoxicity or body weight loss. ICP-AAS revealed significant preferential tumor accumulation of platinum with reduced biodistribution to the kidney or liver following PIMA–GA–DACH–platinum nanoparticle administration as compared with free oxaliplatin. These results indicate that the rational engineering of a novel polymeric nanoparticle inspired by the bioactivation of oxaliplatin results in increased antitumor potency with reduced systemic toxicity compared with the parent cytotoxic. Rational design can emerge as an exciting strategy in the synthesis of nanomedicines for cancer chemotherapy. (paper)

  4. Nanoparticle incorporation of melittin reduces sperm and vaginal epithelium cytotoxicity.

    Directory of Open Access Journals (Sweden)

    Andrew P Jallouk

    Full Text Available Melittin is a cytolytic peptide component of bee venom which rapidly integrates into lipid bilayers and forms pores resulting in osmotic lysis. While the therapeutic utility of free melittin is limited by its cytotoxicity, incorporation of melittin into the lipid shell of a perfluorocarbon nanoparticle has been shown to reduce its toxicity in vivo. Our group has previously demonstrated that perfluorocarbon nanoparticles containing melittin at concentrations <10 µM inhibit HIV infectivity in vitro. In the current study, we assessed the impact of blank and melittin-containing perfluorocarbon nanoparticles on sperm motility and the viability of both sperm and vaginal epithelial cells. We found that free melittin was toxic to sperm and vaginal epithelium at concentrations greater than 2 µM (p<0.001. However, melittin nanoparticles were not cytotoxic to sperm (p = 0.42 or vaginal epithelium (p = 0.48 at an equivalent melittin concentration of 10 µM. Thus, nanoparticle formulation of melittin reduced melittin cytotoxicity fivefold and prevented melittin toxicity at concentrations previously shown to inhibit HIV infectivity. Melittin nanoparticles were toxic to vaginal epithelium at equivalent melittin concentrations ≥20 µM (p<0.001 and were toxic to sperm at equivalent melittin concentrations ≥40 µM (p<0.001. Sperm cytotoxicity was enhanced by targeting of the nanoparticles to the sperm surface antigen sperm adhesion molecule 1. While further testing is needed to determine the extent of cytotoxicity in a more physiologically relevant model system, these results suggest that melittin-containing nanoparticles could form the basis of a virucide that is not toxic to sperm and vaginal epithelium. This virucide would be beneficial for HIV serodiscordant couples seeking to achieve natural pregnancy.

  5. Nanoparticle Incorporation of Melittin Reduces Sperm and Vaginal Epithelium Cytotoxicity

    Science.gov (United States)

    Jallouk, Andrew P.; Moley, Kelle H.; Omurtag, Kenan; Hu, Grace; Lanza, Gregory M.; Wickline, Samuel A.; Hood, Joshua L.

    2014-01-01

    Melittin is a cytolytic peptide component of bee venom which rapidly integrates into lipid bilayers and forms pores resulting in osmotic lysis. While the therapeutic utility of free melittin is limited by its cytotoxicity, incorporation of melittin into the lipid shell of a perfluorocarbon nanoparticle has been shown to reduce its toxicity in vivo. Our group has previously demonstrated that perfluorocarbon nanoparticles containing melittin at concentrations <10 µM inhibit HIV infectivity in vitro. In the current study, we assessed the impact of blank and melittin-containing perfluorocarbon nanoparticles on sperm motility and the viability of both sperm and vaginal epithelial cells. We found that free melittin was toxic to sperm and vaginal epithelium at concentrations greater than 2 µM (p<0.001). However, melittin nanoparticles were not cytotoxic to sperm (p = 0.42) or vaginal epithelium (p = 0.48) at an equivalent melittin concentration of 10 µM. Thus, nanoparticle formulation of melittin reduced melittin cytotoxicity fivefold and prevented melittin toxicity at concentrations previously shown to inhibit HIV infectivity. Melittin nanoparticles were toxic to vaginal epithelium at equivalent melittin concentrations ≥20 µM (p<0.001) and were toxic to sperm at equivalent melittin concentrations ≥40 µM (p<0.001). Sperm cytotoxicity was enhanced by targeting of the nanoparticles to the sperm surface antigen sperm adhesion molecule 1. While further testing is needed to determine the extent of cytotoxicity in a more physiologically relevant model system, these results suggest that melittin-containing nanoparticles could form the basis of a virucide that is not toxic to sperm and vaginal epithelium. This virucide would be beneficial for HIV serodiscordant couples seeking to achieve natural pregnancy. PMID:24748389

  6. Stability of Decontamination Foam Containing Silica Nanoparticles and Viscosifier

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, In Ho; Jung, Chong Hun; Yoon, Suk Bon; Kim, Chorong; Jung, Jun Young; Park, Sang Yoon; Moon, Jei Kwon; Choi, Wang Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-10-15

    This formulation can significantly decrease the amounts of chemical reagents and secondary waste. The advantage of decontamination foam is its potentially wide application for metallic walls, overhead surfaces, and the elements of complex components and facilities. In addition, foam is a good material for in situ decontamination because it generates low final waste volumes owing to its volume expansion. The application of foam allows for remote decontamination processing using only an injection nozzle and the equipment to generate the decontamination foam, which reduces operator exposure to high radioactivity. The decontamination efficiency can be enhanced by improving the contact time between chemical reagents and a contaminated surface through the addition of surfactants and viscosifiers into the decontamination foam. The objective of this study is to investigate the effect of silica nanoparticles and a viscosifier on the foam stability and the dissolution behaviors of corroded specimens using a non-ionic surfactant. This study showed the effect of viscosifiers and nanoparticles on the foam stability when developing new formulations of decontamination foam. The addition of xanthan gum and the mixture of xanthan gum and silica nanoparticles (M-5) significantly increased the foam stability, compared to the surfactant solution alone. This result indicates that both the viscosifier and nanoparticles have a synergistic effect on the foam stability. As the contact time increased, the dissolution rate increased to become similar to the dissolution that contained decontamination liquid.

  7. Lipid Based Formulations of Biopharmaceutics Classification System (BCS Class II Drugs: Strategy, Formulations, Methods and Saturation

    Directory of Open Access Journals (Sweden)

    Šoltýsová I.

    2016-12-01

    Full Text Available Active ingredients in pharmaceuticals differ by their physico-chemical properties and their bioavailability therefore varies. The most frequently used and most convenient way of administration of medicines is oral, however many drugs are little soluble in water. Thus they are not sufficiently effective and suitable for such administration. For this reason a system of lipid based formulations (LBF was developed. Series of formulations were prepared and tested in water and biorelevant media. On the basis of selection criteria, there were selected formulations with the best emulsification potential, good dispersion in the environment and physical stability. Samples of structurally different drugs included in the Class II of the Biopharmaceutics classification system (BCS were obtained, namely Griseofulvin, Glibenclamide, Carbamazepine, Haloperidol, Itraconazol, Triclosan, Praziquantel and Rifaximin, for testing of maximal saturation in formulations prepared from commercially available excipients. Methods were developed for preparation of formulations, observation of emulsification and its description, determination of maximum solubility of drug samples in the respective formulation and subsequent analysis. Saturation of formulations with drugs showed that formulations 80 % XA and 20 % Xh, 35 % XF and 65 % Xh were best able to dissolve the drugs which supports the hypothesis that it is desirable to identify limited series of formulations which could be generally applied for this purpose.

  8. Optical properties of nanoparticles

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    At the NBI I am involved in projects relating to optical properties of metallic nanoparticles in particular with respect to plasmonic heating with direct applications to photothermal cancer therapy. For this purpose we have developed heating assays that can be used to measure the heating of any...... nanoscopic heat source like an irradiated nanoparticle...

  9. High-Level Waste Glass Formulation Model Sensitivity Study 2009 Glass Formulation Model Versus 1996 Glass Formulation Model

    International Nuclear Information System (INIS)

    Belsher, J.D.; Meinert, F.L.

    2009-01-01

    This document presents the differences between two HLW glass formulation models (GFM): The 1996 GFM and 2009 GFM. A glass formulation model is a collection of glass property correlations and associated limits, as well as model validity and solubility constraints; it uses the pretreated HLW feed composition to predict the amount and composition of glass forming additives necessary to produce acceptable HLW glass. The 2009 GFM presented in this report was constructed as a nonlinear optimization calculation based on updated glass property data and solubility limits described in PNNL-18501 (2009). Key mission drivers such as the total mass of HLW glass and waste oxide loading are compared between the two glass formulation models. In addition, a sensitivity study was performed within the 2009 GFM to determine the effect of relaxing various constraints on the predicted mass of the HLW glass.

  10. Marshall Convergent Spray Formulation Improvement for High Temperatures

    Science.gov (United States)

    Scarpa, Jack; Patterson,Chat

    2011-01-01

    The Marshall Convergent Coating-1 (MCC-1) formulation was produced in the 1990s, and uses a standard bisphenol A epoxy resin system with a triamine accelerator. With the increasing heat rates forecast for the next generation of vehicles, higher-temperature sprayable coatings are needed. This work substitutes the low-temperature epoxy resins used in the MCC-1 coating with epoxy phenolic, epoxy novalac, or resorcinolinic resins (higher carbon content), which will produce a higher char yield upon exposure to high heat and increased glass transition temperature. High-temperature filler materials, such as granular cork and glass ecospheres, are also incorporated as part of the convergent spray process, but other sacrificial (ablative) materials are possible. In addition, the use of polyhedral oligomeric silsesquioxanes (POSS) nanoparticle hybrids will increase both reinforcement aspects and contribute to creating a tougher silacious char, which will reduce recession at higher heat rates. Use of expanding epoxy resin (lightweight MCC) systems are also useful in that they reduce system weight, have greater insulative properties, and a decrease in application times can be realized.

  11. Nanotechnology Formulations for Antibacterial Free Fatty Acids and Monoglycerides

    Directory of Open Access Journals (Sweden)

    Joshua A. Jackman

    2016-03-01

    Full Text Available Free fatty acids and monoglycerides have long been known to possess broad-spectrum antibacterial activity that is based on lytic behavior against bacterial cell membranes. Considering the growing challenges of drug-resistant bacteria and the need for new classes of antibiotics, the wide prevalence, affordable cost, and broad spectrum of fatty acids and monoglycerides make them attractive agents to develop for healthcare and biotechnology applications. The aim of this review is to provide a brief introduction to the history of antimicrobial lipids and their current status and challenges, and to present a detailed discussion of ongoing research efforts to develop nanotechnology formulations of fatty acids and monoglycerides that enable superior in vitro and in vivo performance. Examples of nano-emulsions, liposomes, solid lipid nanoparticles, and controlled release hydrogels are presented in order to highlight the potential that lies ahead for fatty acids and monoglycerides as next-generation antibacterial solutions. Possible application routes and future directions in research and development are also discussed.

  12. Drug nanosuspensions: a ZIP tool between traditional and innovative pharmaceutical formulations.

    Science.gov (United States)

    Leone, Federica; Cavalli, Roberta

    2015-01-01

    A nanosuspension or nanocrystal suspension is a versatile formulation combining conventional and innovative features. It comprises 100% pure drug nanoparticles with sizes in the nano-scale range, generally stabilized by surfactants or polymers. Nanosuspensions are usually obtained in liquid media with bottom-up and top-down methods or by their combination. They have been designed to enhance the solubility, the dissolution rate and the bioavailability of drugs via various administration routes. Due to their small sizes, nanosuspensions can be also considered a drug delivery nanotechnology for the preparation of nanomedicine products. This review focuses on the state of the art of the nanocrystal-based formulation. It describes theory characteristics, design parameters, preparation methods, stability issues, as well as specific in vivo applications. Innovative strategies proposed to obtain nanomedicine formulation using nanocrystals are also reported. Many drug nanodelivery systems have been developed to increase the bioavailability of drugs and to decrease adverse side effects, but few can be industrially manufactured. Nanocrystals can close this gap by combining traditional and innovative drug formulations. Indeed, they can be used in many pharmaceutical dosage forms as such, or developed as new nano-scaled products. Engineered surface nanocrystals have recently been proposed as a dual strategy for stability enhancement and targeting delivery of nanocrystals.

  13. Single Nanoparticle Plasmonic Sensors

    Directory of Open Access Journals (Sweden)

    Manish Sriram

    2015-10-01

    Full Text Available The adoption of plasmonic nanomaterials in optical sensors, coupled with the advances in detection techniques, has opened the way for biosensing with single plasmonic particles. Single nanoparticle sensors offer the potential to analyse biochemical interactions at a single-molecule level, thereby allowing us to capture even more information than ensemble measurements. We introduce the concepts behind single nanoparticle sensing and how the localised surface plasmon resonances of these nanoparticles are dependent upon their materials, shape and size. Then we outline the different synthetic approaches, like citrate reduction, seed-mediated and seedless growth, that enable the synthesis of gold and silver nanospheres, nanorods, nanostars, nanoprisms and other nanostructures with tunable sizes. Further, we go into the aspects related to purification and functionalisation of nanoparticles, prior to the fabrication of sensing surfaces. Finally, the recent developments in single nanoparticle detection, spectroscopy and sensing applications are discussed.

  14. Magnetic interactions between nanoparticles

    DEFF Research Database (Denmark)

    Mørup, Steen; Hansen, Mikkel Fougt; Frandsen, Cathrine

    2010-01-01

    We present a short overview of the influence of inter-particle interactions on the properties of magnetic nanoparticles. Strong magnetic dipole interactions between ferromagnetic or ferrimagnetic particles, that would be superparamagnetic if isolated, can result in a collective state...... of nanoparticles. This collective state has many similarities to spin-glasses. In samples of aggregated magnetic nanoparticles, exchange interactions are often important and this can also lead to a strong suppression of superparamagnetic relaxation. The temperature dependence of the order parameter in samples...... of strongly interacting hematite nanoparticles or goethite grains is well described by a simple mean field model. Exchange interactions between nanoparticles with different orientations of the easy axes can also result in a rotation of the sub-lattice magnetization directions....

  15. Functionalized magnetic nanoparticles for biomedical applications.

    Science.gov (United States)

    Gudovan, Dragoș; Balaure, Paul Cătălin; Mihăiescu, Dan Eduard; Fudulu, Adrian; Purcăreanu, Bogdan; Radu, Mihai

    2015-01-01

    Functionalized magnetic nanoparticles followed two main directions in the field of biomedical applications: one direction is as image enhancing agents for magnetic resonance imaging (MRI) and the other is as drugdelivery devices for various biologically-active substances. A third field which just emerges in nanomedicine is the field of the so-called theranostic devices which combines in the same delivery vehicle both the therapeutic agent and the contrast substance. The advantages of using nanoparticles instead of larger carriers for delivery of both drug and image contrast enhancing agents will be highlighted throughout this review article. Despite the ever increasing number of articles reporting both in vitro and in vivo studies carried out on functionalized magnetic nanoparticles and envisaging their potential biomedical applications, only few formulations reached the phase of clinical trials and even fewer became marketed products. The perspectives in the field are open, since new drugs require new delivery devices and possibly new means of functionalization. At the same time, the field of nanomedicine also provides the opportunity to better exploit drugs that are already in clinical use by improving their bioavailability through appropriate nanoformulations.

  16. Self-Setting Calcium Orthophosphate Formulations

    Science.gov (United States)

    Dorozhkin, Sergey V.

    2013-01-01

    In early 1980s, researchers discovered self-setting calcium orthophosphate cements, which are bioactive and biodegradable grafting bioceramics in the form of a powder and a liquid. After mixing, both phases form pastes, which set and harden forming either a non-stoichiometric calcium deficient hydroxyapatite or brushite. Since both of them are remarkably biocompartible, bioresorbable and osteoconductive, self-setting calcium orthophosphate formulations appear to be promising bioceramics for bone grafting. Furthermore, such formulations possess excellent molding capabilities, easy manipulation and nearly perfect adaptation to the complex shapes of bone defects, followed by gradual bioresorption and new bone formation. In addition, reinforced formulations have been introduced, which might be described as calcium orthophosphate concretes. The discovery of self-setting properties opened up a new era in the medical application of calcium orthophosphates and many commercial trademarks have been introduced as a result. Currently such formulations are widely used as synthetic bone grafts, with several advantages, such as pourability and injectability. Moreover, their low-temperature setting reactions and intrinsic porosity allow loading by drugs, biomolecules and even cells for tissue engineering purposes. In this review, an insight into the self-setting calcium orthophosphate formulations, as excellent bioceramics suitable for both dental and bone grafting applications, has been provided. PMID:24956191

  17. Bioequivalence assessment of two formulations of ibuprofen

    KAUST Repository

    Al-Talla, Zeyad

    2011-10-19

    Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz , produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen , manufactured by Boots Company, Nottingham, UK. Methods and results: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference) of ibuprofen (100 mg ibuprofen/5 mL suspension) were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC) parameters were found to be within the predetermined acceptable interval of 80%-125% set by the US Food and Drug Administration. Conclusion: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and, therefore, Doloraz was considered bioequivalent to Brufen. 2011 Al-Talla et al, publisher and licensee Dove Medical Press Ltd.

  18. Functional Magnetic Nanoparticles

    Science.gov (United States)

    Gass, James

    Nanoparticle system research and characterization is the focal point of this research and dissertation. In the research presented here, magnetite, cobalt, and ferrite nanoparticle systems have been explored in regard to their magnetocaloric effect (MCE) properties, as well as for use in polymer composites. Both areas of study have potential applications across a wide variety of interdisciplinary fields. Magnetite nanoparticles have been successfully dispersed in a polymer. The surface chemistry of the magnetic nanoparticle proves critical to obtaining a homogenous and well separated high density dispersion in PMMA. Theoretical studies found in the literature have indicated that surface interface energy is a critical component in dispersion. Oleic acid is used to alter the surface of magnetite nanoparticles and successfully achieve good dispersion in a PMMA thin film. Polypyrrole is then coated onto the PMMA composite layer. The bilayer is characterized using cross-sectional TEM, cross-sectional SEM, magnetic characterization, and low frequency conductivity. The results show that the superparmagnetic properties of the as synthesized particles are maintained in the composite. With further study of the properties of these nanoparticles for real and functional uses, MCE is studied on a variety of magnetic nanoparticle systems. Magnetite, manganese zinc ferrite, and cobalt ferrite systems show significant broadening of the MCE and the ability to tune the peak temperature of MCE by varying the size of the nanoparticles. Four distinct systems are studied including cobalt, cobalt core silver shell nanoparticles, nickel ferrite, and ball milled zinc ferrite. The results demonstrate the importance of surface characteristics on MCE. Surface spin disorder appears to have a large influence on the low temperature magnetic and magnetocalorie characteristics of these nanoparticle systems.

  19. Topical nanoparticulate formulation of drugs for ocular keratitis

    Science.gov (United States)

    Yang, Xiaoyan

    The primary objective of this project is to develop drug-loaded polymeric nanoparticles suspended in a biocompatible gel for topical delivery of therapeutic agents commonly employed in the treatment of ocular viral/bacterial keratitis. PART 1: Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) of dipeptide monoester prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV), D-Val-L-Val-GCV (DLGCV) were formulated and dispersed in thermosensitive PLGA-PEG-PLGA polymer gel for the treatment of herpes simplex virus type 1 (HSV-1) induced viral corneal keratitis. NP containing prodrugs of GCV were prepared by a double-emulsion solvent evaporation technique using various PLGA polymers with different drug/polymer ratios. Cytotoxicity studies suggested that all NP formulations are non-toxic. In vitro release of prodrugs from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when NP were suspended in thermosensitive gels with near zero-order release kinetics. Prodrugs-loaded PLGA NP dispersed in thermosensitive gels can thus serve as a promising drug delivery system for the treatment of anterior eye diseases. Maximum uptake (around 60%) was noted at 3 h for NP. Cellular uptake and intracellular accumulation of prodrugs are significantly different among three stereoisomeric dipeptide prodrugs. The microscopic images show that NP are avidly internalized by HCEC cells and distributed throughout the cytoplasm instead of being localized on the cell surface. Following cellular uptake, prodrugs released from NP gradually bioreversed into parent drug GCV. LLGCV showed the highest degradation rate, followed by LDGCV and DLGCV. LLGCV, LDGCV and DLGCV released from NP exhibited superior uptake and bioreversion in corneal cells. PART 2: PLGA NP of hydrocortisone butyrate (HB) suspended in thermosensitive PLGA-PEG-PLGA gel were developed for the treatment of

  20. A novel molluscicidal formulation of niclosamide.

    Science.gov (United States)

    Dai, Jian-Rong; Wang, Wei; Liang, You-Sheng; Li, Hong-Jun; Guan, Xiao-Hong; Zhu, Yin-Chang

    2008-07-01

    Snail control by molluscicides is an important strategy for schistosomiasis control in China. Currently, only one chemical molluscicide, niclosamide, which is used as 50% wettable powder of niclosamide ethanolamine salt (WPN), is commercially available for field snail control in China. However, WPN is costly, toxic, and has a lower dispersibility and precipitates rapidly. In this paper, we describe the development of a novel formulation of niclosamide, a suspension concentrate of niclosamide (SCN). The efficacy of SCN was evaluated both in the laboratory and field. SCN showed better molluscicidal effects than conventional formulation of WPN, as determined by LC(50) for adult snails, young snails, and snail eggs. The acute toxicity of SCN to Brachdanio rerio hamiton was less than WPN. In conclusion, the novel formulation of SCN suspension is physically more stable, more effective, and less toxic. Therefore, it can be more useful for controlling snails in endemic areas of schistosomiasis in China.

  1. Engaged Problem Formulation in IS Research

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Persson, John Stouby

    2016-01-01

    problems requires a more substantial engagement with the different stakeholders, especially when their problems are ill structured and situated in complex organizational settings. On this basis, we present an engaged approach to formulating IS problems with, not for, IS practitioners. We have come...... to understand engaged problem formulation as joint researching and as the defining of contemporary and complex problems by researchers and those practitioners who experience and know these problems. We used this approach in investigating IS management in Danish municipalities. In this paper, we present...... the approach to formulating problems in an engaged way. We discuss it in relation to ideas and assumptions that underpin engaged scholarship, and we discuss the implications for IS action research, design science research, and mixed approaches....

  2. Engaged Problem Formulation in IS Research

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Persson, John Stouby

    2016-01-01

    “Is this the problem?”: the question that haunts many information systems (IS) researchers when they pursue work relevant to both practice and research. Nevertheless, a deliberate answer to this question requires more than simply asking the involved IS practitioners. Deliberately formulating prob...... the approach to formulating problems in an engaged way. We discuss it in relation to ideas and assumptions that underpin engaged scholarship, and we discuss the implications for IS action research, design science research, and mixed approaches....... to understand engaged problem formulation as joint researching and as the defining of contemporary and complex problems by researchers and those practitioners who experience and know these problems. We used this approach in investigating IS management in Danish municipalities. In this paper, we present...

  3. Microemulsion Synthesis of Nanoparticles

    Directory of Open Access Journals (Sweden)

    Gotić, M.

    2013-11-01

    Full Text Available Nanoparticles and nanomaterials have wide applications in electronics, physics, material design, being also utilized as sensors, catalysts, and more and more in biomedicine. Microemulsions are an exceptionally suitable medium for the synthesis of nanoparticles due to their thermodynamical stability, great solubility of both polar and nonpolar components, as well as their ability to control the size, dispersity and shape of the particles. This review presents microemulsion techniques for the synthesis of inorganic nanoparticles. It takes place in water-in-oil microemulsions by mixing one microemulsion with a cationic precursor, and the other with a precipitating or reducing agent, or by direct addition of reducing agents or gas (O2, NH3 ili CO2 into microemul sion (Fig. 1. Metal nanoparticles are used as catalysts, sensors, ferrofluids etc. They are produced by reducing the metal cation with a suitable reducing agent. In a similar way, one can prepare nanoparticles of alloys from the metal salts, provided that the metals are mutually soluble. The microemulsion technique is also suitable for depositing nanoparticles onto various surfaces. Highly active catalysts made from nanoparticles of Pt, Pd, Rh and other noble metals may be obtained in this way. Metal oxides and hydroxides may be prepared by hydrolysis or precipitation in the water core of microemulsion. Precipitation can be initiated by adding the base or precipitating agent into the microemulsion with water solution of metal ions. Similarly, nanoparticles may be prepared of sulphides, halogenides, cyanides, carbonates, sulphates and other insoluble metal salts. To prevent oxidation of nanoparticles, especially Fe, the particles are coated with inert metals, oxides, various polymers etc. Coating may provide additional functionality; e.g. coating with gold allows subsequent functionalization with organic compounds containing sulphur, due to the strong Au–S bond. Polymer coatings decrease

  4. RAACFDb: Rheumatoid arthritis ayurvedic classical formulations database.

    Science.gov (United States)

    Mohamed Thoufic Ali, A M; Agrawal, Aakash; Sajitha Lulu, S; Mohana Priya, A; Vino, S

    2017-02-02

    In the past years, the treatment of rheumatoid arthritis (RA) has undergone remarkable changes in all therapeutic modes. The present newfangled care in clinical research is to determine and to pick a new track for better treatment options for RA. Recent ethnopharmacological investigations revealed that traditional herbal remedies are the most preferred modality of complementary and alternative medicine (CAM). However, several ayurvedic modes of treatments and formulations for RA are not much studied and documented from Indian traditional system of medicine. Therefore, this directed us to develop an integrated database, RAACFDb (acronym: Rheumatoid Arthritis Ayurvedic Classical Formulations Database) by consolidating data from the repository of Vedic Samhita - The Ayurveda to retrieve the available formulations information easily. Literature data was gathered using several search engines and from ayurvedic practitioners for loading information in the database. In order to represent the collected information about classical ayurvedic formulations, an integrated database is constructed and implemented on a MySQL and PHP back-end. The database is supported by describing all the ayurvedic classical formulations for the treatment rheumatoid arthritis. It includes composition, usage, plant parts used, active ingredients present in the composition and their structures. The prime objective is to locate ayurvedic formulations proven to be quite successful and highly effective among the patients with reduced side effects. The database (freely available at www.beta.vit.ac.in/raacfdb/index.html) hopefully enables easy access for clinical researchers and students to discover novel leads with reduced side effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Effects of Formulation Variables and Storage Conditions on Light Protected Vitamin B12 Mixed Parenteral Formulations

    Directory of Open Access Journals (Sweden)

    Farnaz Monajjemzadeh

    2014-12-01

    Full Text Available Purpose: In this research the effect of vitamin B1 and B6 on cyanocobalamin stability in commercial light protected parenteral formulations and upon adding stabilizing agents will be investigated and best formulation composition and proper storage condition will be introduced. Methods: In this research some additives such as co solvents and tonicity adjusters, surfactants, antioxidants and chelating agents as well as buffer solutions, were used to improve the stability of the parenteral mixed formulations of B12 in the presence of other B vitamins (B1 and B6. Screening tests and accelerated stability tests were performed according to ICH guidelines Q1A (R2. Results: Shelf life evaluation revealed the best formulation and the proper storage condition. The results indicated the first kinetic models for all tested formulations and the optimum pH value was determined to be 5.8. There was no evidence of B12 loss when mixed with B1 and B6 in a medical syringe at room temperature for maximum of 8 hours. Conclusion: It is necessary to formulate vitamin B12 mixed parenteral solutions using proper phosphate buffers (pH=5.8 and to indicate “Store in refrigerator” on the mixed parenteral formulations of vitamin B12 with other B vitamins, which has not been expressed on the label of tested Brand formulations at the time of this study.

  6. Formulation and stability testing of photolabile drugs.

    Science.gov (United States)

    Tønnesen, H H

    2001-08-28

    Exposure of a drug to irradiation can influence the stability of the formulation, leading to changes in the physicochemical properties of the product. The influence of excipients of frequently used stabilizers is often difficult to predict and, therefore, stability testing of the final preparation is important. The selection of a protective packaging must be based on knowledge about the wavelength causing the instability. Details on drug photoreactivity will also be helpful in order to minimize side-effects and/or optimize drug targeting by developing photoresponsive drug delivery systems. This review focuses on practical problems related to formulation and stability testing of photolabile drugs.

  7. Quaternionic formulation of the exact parity model

    International Nuclear Information System (INIS)

    Brumby, S.P.; Foot, R.; Volkas, R.R.

    1996-01-01

    The exact parity model (EPM) is a simple extension of the standard model which reinstates parity invariance as an unbroken symmetry of nature. The mirror matter sector of the model can interact with ordinary matter through gauge boson mixing, Higgs boson mixing and, if neutrinos are massive, through neutrino mixing. The last effect has experimental support through the observed solar and atmospheric neutrino anomalies. In the paper it is shown that the exact parity model can be formulated in a quaternionic framework. This suggests that the idea of mirror matter and exact parity may have profound implications for the mathematical formulation of quantum theory. 13 refs

  8. Pharmacokinetics of formulated tenoxicam transdermal delivery systems.

    Science.gov (United States)

    Kim, Taekyung; Kang, Eunyoung; Chun, Inkoo; Gwak, Hyesun

    2008-01-01

    To investigate the feasibility of developing a new tenoxicam transdermal delivery system (TDS), the pharmacokinetics of tenoxicam from various formulated TDS were evaluated and compared with values following oral administration of tenoxicam and with application of a piroxicam plaster (Trast) marketed in Korea. Based on previous in-vitro study results, a mixture of diethylene glycol monoethyl ether (DGME) and propylene glycol monolaurate (PGML) (40:60) was used as a vehicle, and caprylic acid, capric acid, lauric acid, oleic acid or linoleic acid (each at 3%) was added as an enhancer. Triethanolamine (5%) was used as a solubilizer, and Duro-Tak 87-2510 as a pressure-sensitive adhesive. Among these fatty acids used for the formulation of tenoxicam TDS, caprylic acid showed the greatest enhancing effect; the area under the plasma concentration-time profile (AUC) decreased in the order of caprylic acid>linoleic acid>or=oleic acid>lauric acid>capric acid. Compared with oral administration, maximum plasma concentration (Cmax) was significantly lower, and time to reach Cmax (Tmax) delayed with all formulated tenoxicam TDS. All formulated TDS resulted in a lower AUC than with the oral formulation, except for TDS containing caprylic acid, although the difference was statistically significant only with capric acid. The AUC for all the formulated tenoxicam TDS was significantly higher than that of the piroxicam plaster; TDS with caprylic acid increased AUC 8.53-fold compared with the piroxicam plaster. Even though the Tmax of tenoxicam TDS was not significantly different from that of the piroxicam plaster, Cmax was higher; formulations containing caprylic acid and linoleic acid increased Cmax by 7.39- and 8.76-fold, respectively. In conclusion, a formulation containing 1.5 mL DGME-PGML (40:60) with 3% caprylic acid and 5% triethanolamine mixed with 6 g Duro-Tak 87-2510 could be a good candidate for developing a new tenoxicam TDS to maintain a comparable extent of absorption

  9. Design of formulated products: a systematic methodology

    DEFF Research Database (Denmark)

    Conte, Elisa; Gani, Rafiqul; Ng, K.M.

    2011-01-01

    -based computer-aided methodology for design and verification of a class of chemical-based products (liquid formulations) is presented. This methodology is part of an integrated three-stage approach for design/verification of liquid formulations where stage-1 generates a list of feasible product candidates and....../or verifies a specified set through a sequence of predefined activities (work-flow). Stage-2 and stage-3 (not presented here) deal with the planning and execution of experiments, for product validation. Four case studies have been developed to test the methodology. The computer-aided design (stage-1...

  10. Boundary layer computations using a generalized formulation

    Science.gov (United States)

    Bergeron, D.; Zingg, D. W.

    A numerical solution procedure for a generalized form of the boundary-layer equations based on the formulation of Steger and Van Dalsem is described. The formulation, which is intended for use in a fortified Navier-Stokes procedure, uses the boundary-layer equations expressed in body-confromal coordinates but transformed into generalized coordinates for the solution process. Results are presented for attached and separated transonic airfoil flows with external pressure gradient given from a Navier-Stokes solution in the boundary layers. Discrepancies are noted near shocks and trailing edges, where normal pressure gradients can be appreciable and streamwise velocity gradients can be high.

  11. Problem formulation as a discursive design activity

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp; Dorst, Kees; Andreasen, Mogens Myrup

    2009-01-01

    part of any engineering design education. Yet the assumptions behind the rational problem solving approach to design do not sit well with some of the experiences we have in design teaching and design practice. Problem formulation is one such area where we might have to look for a different way...... the intricacies of problem formulation in design. Key notions in design methodology, like ‘design problem’, ‘design solution’ and ‘ill-structuredness’ are reconsidered in this light. This directly leads to identifying further lines for investigation, and an agenda for design research....

  12. An exact approach for aggregated formulations

    DEFF Research Database (Denmark)

    Gamst, Mette; Spoorendonk, Simon

    Aggregating formulations is a powerful approach for transforming problems into taking more tractable forms. Aggregated formulations can, though, have drawbacks: some information may get lost in the aggregation and { put in a branch-and-bound context { branching may become very di_cult and even....... The paper includes general considerations on types of problems for which the method is of particular interest. Furthermore, we prove the correctness of the procedure and consider how to include extensions such as cutting planes and advanced branching strategies....

  13. Effects of 14-day oral low dose selenium nanoparticles and selenite in rat—as determined by metabolite pattern determination

    Directory of Open Access Journals (Sweden)

    Niels Hadrup

    2016-10-01

    Full Text Available Selenium (Se is an essential element with a small difference between physiological and toxic doses. To provide more effective and safe Se dosing regimens, as compared to dosing with ionic selenium, nanoparticle formulations have been developed. However, due to the nano-formulation, unexpected toxic effects may occur. We used metabolite pattern determination in urine to investigate biological and/or toxic effects in rats administered nanoparticles and for comparison included ionic selenium at an equimolar dose in the form of sodium selenite. Low doses of 10 and 100 fold the recommended human high level were employed to study the effects at borderline toxicity. Evaluations of all significantly changed putative metabolites, showed that Se nanoparticles and sodium selenite induced similar dose dependent changes of the metabolite pattern. Putative identified metabolites included increased decenedioic acid and hydroxydecanedioic acid for both Se formulations whereas dipeptides were only increased for selenite. These effects could reflect altered fatty acid and protein metabolism, respectively.

  14. Carboxymethyl guar gum nanoparticles for drug delivery applications: Preparation and preliminary in-vitro investigations

    International Nuclear Information System (INIS)

    Dodi, G.; Pala, A.; Barbu, E.; Peptanariu, D.; Hritcu, D.; Popa, M.I.; Tamba, B.I.

    2016-01-01

    Carboxymethyl guar gum (CMGG) synthesized from commercially available polysaccharide was formulated into nanoparticles via ionic gelation using trisodium trimetaphosphate (STMP) as cross-linking agent. Characterisation using a range of analytical techniques (FTIR, NMR, GPC, TGA and DLS) confirmed the CMGG structure and revealed the effect of the CMGG and STMP concentration on the main characteristics of the obtained nanoformulations. The average nanoparticle diameter was found to be around 208 nm, as determined by dynamic light scattering (DLS) and confirmed by scanning electron microscopy (SEM) and nanoparticle tracking analysis (NTA). Experiments using simulated gastric and intestinal fluids evidenced significant pH-dependent drug release behaviour of the nanoformulations loaded with Rhodamine B (RhB) as a model drug (loading capacity in excess of 83%), as monitored by UV–Vis. While dose-dependent cytotoxicity was observed, the nanoformulations appeared completely non-toxic at concentrations below 0.3 mg/mL. Results obtained so far suggest that carboxymethylated guar gum nanoparticles formulated with STMP warrant further investigations as polysaccharide based biocompatible drug nanocarriers. - Highlights: • Carboxymethyl guar gum nanoparticles preparation by ionic gelation • The optimum synthesis system designed particles around 200 nm • The nanoformulations appeared completely non-toxic at specific concentrations • The loaded formulations evidenced significant pH-dependent drug release behaviour • The results encourage further investigations as polysaccharidic drug nanocarriers

  15. Exploring the Preparation of Albendazole-Loaded Chitosan-Tripolyphosphate Nanoparticles

    Directory of Open Access Journals (Sweden)

    Bong-Seok Kang

    2015-02-01

    Full Text Available The objective of this study was to improve the solubility of albendazole and optimize the preparation of an oral nanoparticle formulation, using β-cyclodextrin (βCD and chitosan-tripolyphosphate (TPP nanoparticles. The solubility of albendazole in buffers, surfactants, and various concentrations of acetic acid solution was investigated. To determine drug loading, the cytotoxic effects of the albendazole concentration in human hepatocellular carcinoma cells (HepG2 were investigated. The formulations were prepared by mixing the drug solution in Tween 20 with the chitosan solution. TPP solution was added dropwise with sonication to produce a nanoparticle through ionic crosslinking. Then the particle size, polydispersity index, and zeta potential of the nanoparticles were investigated to obtain an optimal composition. The solubility of albendazole was greater in pH 2 buffer, Tween 20, and βCD depending on the concentration of acetic acid. Drug loading was determined as 100 µg/mL based on the results of cell viability. The optimized ratio of Tween 20, chitosan/hydroxypropyl βCD, and TPP was 2:5:1, which resulted in smaller particle size and proper zeta positive values of the zeta potential. The chitosan-TPP nanoparticles increased the drug solubility and had a small particle size with homogeneity in formulating albendazole as a potential anticancer agent.

  16. Carboxymethyl guar gum nanoparticles for drug delivery applications: Preparation and preliminary in-vitro investigations

    Energy Technology Data Exchange (ETDEWEB)

    Dodi, G., E-mail: gianina.dodi@yahoo.co.uk [“Gheorghe Asachi” Technical University of Iasi (Romania); SCIENT — Research Centre for Instrumental Analysis, Bucharest (Romania); Pala, A. [University of Sassari, Sassari (Italy); Barbu, E. [University of Portsmouth, Portsmouth (United Kingdom); Peptanariu, D. [“Petru Poni” Institute of Macromolecular Chemistry, Iasi (Romania); Hritcu, D.; Popa, M.I. [“Gheorghe Asachi” Technical University of Iasi (Romania); Tamba, B.I. [“Gr. T. Popa” University of Medicine and Pharmacy, Iasi (Romania)

    2016-06-01

    Carboxymethyl guar gum (CMGG) synthesized from commercially available polysaccharide was formulated into nanoparticles via ionic gelation using trisodium trimetaphosphate (STMP) as cross-linking agent. Characterisation using a range of analytical techniques (FTIR, NMR, GPC, TGA and DLS) confirmed the CMGG structure and revealed the effect of the CMGG and STMP concentration on the main characteristics of the obtained nanoformulations. The average nanoparticle diameter was found to be around 208 nm, as determined by dynamic light scattering (DLS) and confirmed by scanning electron microscopy (SEM) and nanoparticle tracking analysis (NTA). Experiments using simulated gastric and intestinal fluids evidenced significant pH-dependent drug release behaviour of the nanoformulations loaded with Rhodamine B (RhB) as a model drug (loading capacity in excess of 83%), as monitored by UV–Vis. While dose-dependent cytotoxicity was observed, the nanoformulations appeared completely non-toxic at concentrations below 0.3 mg/mL. Results obtained so far suggest that carboxymethylated guar gum nanoparticles formulated with STMP warrant further investigations as polysaccharide based biocompatible drug nanocarriers. - Highlights: • Carboxymethyl guar gum nanoparticles preparation by ionic gelation • The optimum synthesis system designed particles around 200 nm • The nanoformulations appeared completely non-toxic at specific concentrations • The loaded formulations evidenced significant pH-dependent drug release behaviour • The results encourage further investigations as polysaccharidic drug nanocarriers.

  17. PLGA 50:50 nanoparticles of paclitaxel: Development, in vitro anti ...

    Indian Academy of Sciences (India)

    lation of novel drug delivery systems to deliver such extreme hydrophobic drug. To formulate nanoparticles which makes suitable to deliver hydrophobic drugs effectively (intravenous) with desired pharmacokinetic profile for breast cancer treatment; in this context in vitro cytotoxic activity was evaluated using BT-549 cell line.

  18. Inclusion of the helper lipid dioleoyl-phosphatidylethanolamine in solid lipid nanoparticles inhibits their transfection efficiency

    NARCIS (Netherlands)

    de Jesus, Marcelo B.; Radaic, Allan; Hinrichs, Wouter L J; Ferreira, Carmen V; de Paula, Eneida; Hoekstra, Dirk; Zuhorn, Inge S

    Solid lipid nanoparticles (SLNs) are a promising system for the delivery of lipophilic and hydrophilic drugs. They consist of a solid lipid core that is stabilized by a layer of surfactants. By the incorporation of cationic lipids in the formulation, positively charged SLNs can be generated, that

  19. Electronically cloaked nanoparticles

    Science.gov (United States)

    Shen, Wenqing

    The concept of electronic cloaking is to design objects invisible to conduction electrons. The approach of electronic cloaking has been recently suggested to design invisible nanoparticle dopants with electronic scattering cross section smaller than 1% of the physical cross section (pi a2), and therefore to enhance the carrier mobility of bulk materials. The proposed nanoparticles have core-shell structures. The dopants are incorporated inside the core, while the shell layer serves both as a spacer to separate the charge carriers from their parent atoms and as a cloaking shell to minimize the scattering cross section of the electrons from the ionized nanoparticles. Thermoelectric materials are usually highly doped to have enough carrier density. Using invisible dopants could achieve larger thermoelectric power factors by enhancing the electronic mobility. Core-shell nanoparticles show an advantage over one-layer nanoparticles, which are proposed in three-dimensional modulation doping. However designing such nanoparticles is not easy as there are too many parameters to be considered. This thesis first shows an approach to design hollow nanoparticles by applying constrains on variables. In the second part, a simple mapping approach is introduced where one can identify possible core-shell particles by comparing the dimensionless parameters of chosen materials with provided maps. In both parts of this work, several designs with realistic materials were made and proven to achieve electronic cloaking. Improvement in the thermoelectric power factor compared to the traditional impurity doping method was demonstrated in several cases.

  20. Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye - Part II - Ocular drug-loaded lipid nanoparticles.

    Science.gov (United States)

    Sánchez-López, E; Espina, M; Doktorovova, S; Souto, E B; García, M L

    2017-01-01

    In the recent decades, various controlled delivery systems have been introduced with the aim to improve solubility, stability and bioavailability of poorly absorbed drugs. Among all, lipid nanoparticles gather interesting properties as drug or gene delivery carriers. These systems, composed either of solid lipids (SLN) or of solid and liquid lipids (NLC) stabilized with surfactants, combine the advantages of other colloidal particles such as polymeric nanoparticles, fat emulsions and liposomes avoiding their main disadvantages. Lipid nanoparticles represent an interesting approach for eye drug delivery as they can improve the corneal absorption of drugs enhancing their bioavailability. The Generally Recognized as Safe status of formulation excipients, the scaling-up facilities and the possibility of sterilization, make them suitable for industrial production. In this review, the latest findings, potential applications, and challenges related to the use of lipid nanoparticles for ocular drug delivery are comprehensively discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Development of biodegradable PLGA nanoparticles surface engineered with hyaluronic acid for targeted delivery of paclitaxel to triple negative breast cancer cells.

    Science.gov (United States)

    Cerqueira, Brenda Brenner S; Lasham, Annette; Shelling, Andrew N; Al-Kassas, Raida

    2017-07-01

    This study aimed at development of poly (lactic-co-glycolic acid) (PLGA) nanoparticles embedded with paclitaxel and coated with hyaluronic acid (HA-PTX-PLGA) to actively target the drug to a triple negative breast cancer cells. Nanoparticles were successfully fabricated using a modified oil-in-water emulsion method. The effect of various formulations parameters on the physicochemical properties of the nanoparticles was investigated. SEM imaging confirmed the spherical shape and nano-scale size of the nanoparticles. A sustained drug release profile was obtained and enhanced PTX cytotoxicity was observed when MDA-MB-231 cells were incubated with the HA-PTX-PLGA formulation compared to cells incubated with the non-HA coated nanoparticles. Moreover, HA-PLGA nanoparticles exhibited improved cellular uptake, based on a possible receptor mediated endocytosis due to interaction of HA with CD44 receptors when compared to non-coated PLGA nanoparticles. The non-haemolytic potential of the nanoparticles indicated the suitability of the developed formulation for intravenous administration. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Application of poly(epsilon-caprolactone) nanoparticles containing atrazine herbicide as an alternative technique to control weeds and reduce damage to the environment.

    Science.gov (United States)

    Pereira, Anderson E S; Grillo, Renato; Mello, Nathalie F S; Rosa, Andre H; Fraceto, Leonardo F

    2014-03-15

    Nanoparticles of poly(epsilon-caprolactone) containing the herbicide atrazine were prepared, characterized, and evaluated in terms of their herbicidal activity and genotoxicity. The stability of the nanoparticles was evaluated over a period of three months, considering the variables: size, polydispersion index, pH, and encapsulation efficiency. Tests on plants were performed with target (Brassica sp.) and non-target (Zea mays) organisms, and the nanoparticle formulations were shown to be effective for the control of the target species. Experiments using soil columns revealed that the use of nanoparticles reduced the mobility of atrazine in the soil. Application of the Allium cepa chromosome aberration assay demonstrated that the nanoparticle systems were able to reduce the genotoxicity of the herbicide. The formulations developed offer a useful means of controlling agricultural weeds, while at the same time reducing the risk of harm to the environment and human health. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Determination of carbamazepine in pharmaceutical formulations

    Directory of Open Access Journals (Sweden)

    Lílian Grace da Silva Solon

    2010-09-01

    Full Text Available The aim of this study was to evaluate the quality of five different solid formulations of carbamazepine. The reference formulation was Tegretol® 200.00 mg (Novartis and the others were: generic formulation of carbamazepine 200.00 mg (National Industry, similar formulation of carbamazepine 200.00 mg (National Industry, and two formulations of carbamazepine 200.00 mg acquired from two different compounding pharmacies. The latter consisted of capsules obtained in Natal, the capital city of the Brazilian State of Rio Grande do Norte. The quality of samples was evaluated through physical and physical-chemical tests, including: weight, diameter, thickness, content, dissolution, disintegration, hardness, friability and moisture. The results of friability analysis showed that all formulations met Brazilian and United States Pharmacopeia (USP specifications. In spite of having a higher hardness compared to the reference, the generic formulation had a lower disintegration time. This could be associated to the presence of crospovidone in its formulation. Results of this study showed that all formulations had dissolutions which were in accordance with Brazilian Pharmacopoeia specifications, and quality control tests. An exception was found for the similar formulation, which had a hardness parameter that exceeded the USP standard. However, this difference was not significant given the similar formulation's satisfactory disintegration time.O objetivo desse trabalho foi avaliar a qualidade de cinco formulações de carbamazepina na dosagem de 200,00 mg: medicamento referência Tegretol® (Novartis, medicamento genérico (indústria nacional, medicamento similar (indústria nacional e cápsulas do mesmo medicamento obtidas de duas farmácias de manipulação da cidade do Natal, RN. Os ensaios realizados foram: peso médio, diâmetro, espessura, teor, dissolução, desintegração, dureza, friabilidade e umidade. Foi observado que nenhuma das amostras

  4. Development of Acyclovir-Loaded Albumin Nanoparticles and Improvement of Acyclovir Permeation Across Human Corneal Epithelial T Cells.

    Science.gov (United States)

    Suwannoi, Panita; Chomnawang, Mullika; Sarisuta, Narong; Reichl, Stephan; Müller-Goymann, Christel C

    2017-12-01

    The aim of the present study was to develop acyclovir (ACV) ocular drug delivery systems of bovine serum albumin (BSA) nanoparticles as well as to assess their in vitro transcorneal permeation across human corneal epithelial (HCE-T) cell multilayers. The ACV-loaded BSA nanoparticles were prepared by desolvation method along with physicochemical characterization, cytotoxicity, as well as in vitro transcorneal permeation studies across HCE-T cell multilayers. The nanoparticles appeared to be spherical in shape and nearly uniform in size of about 200 nm. The size of nanoparticles became smaller with decreasing BSA concentration, while the ratios of water to ethanol seemed not to affect the size. Increasing the amount of ethanol in desolvation process led to significant reduction of drug entrapment of nanoparticles with smaller size and more uniformity. The ACV-loaded BSA nanoparticles prepared were shown to have no cytotoxic effect on HCE-T cells used in permeation studies. The in vitro transcorneal permeation results revealed that ACV could permeate through the HCE-T cell multilayers significantly higher from BSA nanoparticles than from aqueous ACV solutions. The ACV-loaded BSA nanoparticles could be prepared by desolvation method without glutaraldehyde in the formulation. ACV could increasingly permeate through the multilayers of HCE-T cells from the ACV-loaded BSA nanoparticles. Therefore, the ACV-loaded BSA nanoparticles could be a highly potential ocular drug delivery system.

  5. Assembling RNA Nanoparticles.

    Science.gov (United States)

    Xiao, Shou-Jun

    2017-01-01

    RNA nanoparticles are designed and self-assembled according to noncanonical interactions of naturally conserved RNA motifs and/or canonical Watson-Crick base-pairing interactions, which have potential applications in gene therapy and nanomedicine. These artificially engineered nanoparticles are mainly synthesized from in vitro transcribed RNAs, purified by denaturing and native polyacrylamide gel electrophoresis (PAGE), and characterized with native PAGE, AFM, and TEM technologies. The protocols of in vitro transcription, denaturing and native PAGE, and RNA nanoparticle self-assembly are described in detail.

  6. Antimicrobial efficacy and ocular cell toxicity from silver nanoparticles.

    Science.gov (United States)

    Santoro, Colleen M; Duchsherer, Nicole L; Grainger, David W

    2007-05-01

    Silver in various forms has long been recognized for antimicrobial properties, both in biomedical devices and in eyes. However, soluble drugs used on the ocular surface are rapidly cleared through tear ducts and eventually ingested, resulting in decreased efficacy of the drug on its target tissue and potential concern for systemic side effects. Silver nanoparticles were studied as a source of anti-microbial silver for possible controlled-release contact lens controlled delivery formulations. Silver ion release over a period of several weeks from nanoparticle sources of various sizes and doses in vitro was evaluated in vitro against Pseudomonas aeruginosa strain PA01. Mammalian cell viability and cytokine expression in response to silver nanoparticle exposure is evaluated using corneal epithelial cells and eye-associated macrophages cultured in vitro in serum-free media. Minimal microcidal and cell toxic effects were observed for several silver nanoparticle suspensions and aqueous extraction times for bulk total silver concentrations commensurate with comparative silver ion (e.g., Ag(+) ((aq))) toxicity. This indicates that (1) silver particles themselves are not microcidal under conditions tested, and (2) insufficient silver ion is generated from these particles at these loadings to produce observable biological effects in these in vitro assays. If dosing allows substantially increased silver particle loading in the lens, the bactericidal efficacy of silver nanoparticles in vitro is one possible approach to limiting bacterial colonization problems associated with extended-wear contact lenses.

  7. Toxicity and biodistribution of orally administered casein nanoparticles.

    Science.gov (United States)

    Gil, Ana Gloria; Irache, Juan Manuel; Peñuelas, Iván; González Navarro, Carlos Javier; López de Cerain, Adela

    2017-08-01

    In the last years, casein nanoparticles have been proposed as carriers for the oral delivery of biologically active compounds. However, till now, no information about their possible specific hazards in vivo was available. The aim of this work was to assess the safety of casein nanoparticles when administered orally to animals through a 90 days dose-repeated toxicity study (OECD guideline 408), that was performed in Wistar rats under GLP conditions. After 90 days, no evidences of significant alterations in animals treated daily with 50, 150 or 500 mg/kg bw of nanoparticles were found. This safety agrees well with the fact that nanoparticles were not absorbed and remained within the gut as observed by radiolabelling in the biodistribution study. After 28 days, there was a generalized hyperchloremia in males and females treated with the highest dose of 500 mg/kg bw, that was coupled with hypernatremia in the females. These effects were related to the presence of mannitol which was used as excipient in the formulation of casein nanoparticles. According to these results, the No Observed Adverse Effect Level (NOAEL) could be established in 150 mg/kg bw/day and the Lowest Observed Effect Level (LOEL) could be established in 500 mg/kg bw/day. Copyright © 2017. Published by Elsevier Ltd.

  8. Preparation and characterization of highly stable lipid nanoparticles with amorphous core of tuneable viscosity.

    Science.gov (United States)

    Delmas, Thomas; Couffin, Anne-Claude; Bayle, Pierre Alain; de Crécy, François; Neumann, Emmanuelle; Vinet, Françoise; Bardet, Michel; Bibette, Jérôme; Texier, Isabelle

    2011-08-15

    Lipid nanoparticles (LNP) have been designed based on low cost and human-use approved excipients, and manufactured by an easy, robust, and up-scalable process. Fluid colloidal dispersions or gel viscous formulations of highly stable nanoparticles (more than 12 month stability is achieved for some formulations) can be obtained. Their physicochemical properties are studied by Dynamic Light Scattering, Differential Scanning Calorimetry, and NMR. The results picture nanoparticles with a non-crystalline core, which viscosity can be finely tuned by the lipid composition and the temperature. A design of experiments has been used to investigate the limits of the system colloidal stability. The impact of core and surfactant weight fractions have been explored both experimentally and using the design of experiments. The versatility of this physicochemical system could open the way to a wide range of future pharmaceutical applications. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents.

    Science.gov (United States)

    Allahverdiyev, Adil M; Kon, Kateryna Volodymyrivna; Abamor, Emrah Sefik; Bagirova, Malahat; Rafailovich, Miriam

    2011-11-01

    The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria.

  10. Characterization of abrasion-induced nanoparticle release from paints into liquids and air

    Science.gov (United States)

    Golanski, L.; Gaborieau, A.; Guiot, A.; Uzu, G.; Chatenet, J.; Tardif, F.

    2011-07-01

    Two standard methods for the characterization of the abrasion nanoparticle release into air and liquid from coatings containing nanoparticles were developed. Details of the abrasion processes and the measurement methods are shown. Paints were formulated in an industrial facility. Standard abrasion conditions in wet environments were simulated. The size distribution of the particles abraded into liquid was analyzed by a laser granulometer: submicrometric and micrometric particles were observed, but no nanometric particles. The nanoparticles released in liquid were deposited on filters for SEM (Scanning Electron Microscopy) analysis. No free or agglomerated nanoparticles were observed by SEM: nanoparticles seem to remain embedded in the paint matrix. The same coatings were abraded in the air using another standard method. The ELPI (Electrical Low Pressure Impactor) was used to determine the number size distribution of the dust generated. Abrasion is found to produce submicrometric and micrometric particles in the air but no nanoparticles. Further characterizations by SEM confirmed that no free or agglomerated nanoparticles were emitted: nanoparticles seem to remain embedded in the paint matrix.

  11. Characterization of abrasion-induced nanoparticle release from paints into liquids and air

    International Nuclear Information System (INIS)

    Golanski, L; Guiot, A; Uzu, G; Tardif, F; Gaborieau, A; Chatenet, J

    2011-01-01

    Two standard methods for the characterization of the abrasion nanoparticle release into air and liquid from coatings containing nanoparticles were developed. Details of the abrasion processes and the measurement methods are shown. Paints were formulated in an industrial facility. Standard abrasion conditions in wet environments were simulated. The size distribution of the particles abraded into liquid was analyzed by a laser granulometer: submicrometric and micrometric particles were observed, but no nanometric particles. The nanoparticles released in liquid were deposited on filters for SEM (Scanning Electron Microscopy) analysis. No free or agglomerated nanoparticles were observed by SEM: nanoparticles seem to remain embedded in the paint matrix. The same coatings were abraded in the air using another standard method. The ELPI (Electrical Low Pressure Impactor) was used to determine the number size distribution of the dust generated. Abrasion is found to produce submicrometric and micrometric particles in the air but no nanoparticles. Further characterizations by SEM confirmed that no free or agglomerated nanoparticles were emitted: nanoparticles seem to remain embedded in the paint matrix.

  12. Lagrangian formulation of classical BMT-theory

    International Nuclear Information System (INIS)

    Pupasov-Maksimov, Andrey; Deriglazov, Alexei; Guzman, Walberto

    2013-01-01

    Full text: The most popular classical theory of electron has been formulated by Bargmann, Michel and Telegdi (BMT) in 1959. The BMT equations give classical relativistic description of a charged particle with spin and anomalous magnetic momentum moving in homogeneous electro-magnetic field. This allows to study spin dynamics of polarized beams in uniform fields. In particular, first experimental measurements of muon anomalous magnetic momentum were done using changing of helicity predicted by BMT equations. Surprisingly enough, a systematic formulation and the analysis of the BMT theory are absent in literature. In the present work we particularly fill this gap by deducing Lagrangian formulation (variational problem) for BMT equations. Various equivalent forms of Lagrangian will be discussed in details. An advantage of the obtained classical model is that the Lagrangian action describes a relativistic spinning particle without Grassmann variables, for both free and interacting cases. This implies also the possibility of canonical quantization. In the interacting case, an arbitrary electromagnetic background may be considered, which generalizes the BMT theory formulated to the case of homogeneous fields. The classical model has two local symmetries, which gives an interesting example of constrained classical dynamics. It is surprising, that the case of vanishing anomalous part of the magnetic momentum is naturally highlighted in our construction. (author)

  13. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The

  14. Formulation and characterization of caffeine biodegradable chewing ...

    African Journals Online (AJOL)

    ) is a test for analysing the textural properties of food, in which the samples are ..... Food Technol 1978;. 32: 62-66. 16. Mehta FM, Trivedi P. Formulation and characterization of biodegradable medicated chewing gum delivery system for motion ...

  15. Formulation and evaluation and terbutaline sulphate and ...

    African Journals Online (AJOL)

    We report the use of low rugosity lactose, product of controlled crystallization of this carrier, in the formulation of terbutaline sulphate and beclomethasone dipropionate dry powder inhalers. The deposition patterns obtained with inhalation mixtures consisting of the modified lactose and each of the micronised drugs ...

  16. Dynamic psychiatry and the psychodynamic formulation

    African Journals Online (AJOL)

    In her book 'An Unquiet Mind' the psychologist Kay Jamison gives a moving ... Department of Psychiatry, University of Pretoria, Weskoppies Hospital, Pretoria, South Africa. Abstract: This ... psychodynamic formulation is unfortunately seldom incorporated in the psychiatric presentation of patients; guidelines are therefore ...

  17. Facile Colorimetric Determination of Duloxetine in Formulations ...

    African Journals Online (AJOL)

    ... the determination of duloxetine hydrochloride (DX). Methods: Ion-pair spectrophotometric method was employed for the determination of duloxetine hydrochloride (DX) in bulk and pharmaceutical formulations using acidic dye methyl orange (MO) as ion-pairing agent at pH 4 (phthalate buffer). The yellow ion-pair complex ...

  18. Yang-Mills formulation of interacting strings

    International Nuclear Information System (INIS)

    Chan Hongmo; Tsou Sheungtsun

    1988-06-01

    A suggestion that the theory of interacting open bosonic string be reformulated as a generalised Yang-Mills theory is further elucidated. Moreover, a serious reservation regarding the ordering of operators in the earlier 'proof' of equivalence between the new and standard formulations is now removed. (author)

  19. State-Space Formulation for Circuit Analysis

    Science.gov (United States)

    Martinez-Marin, T.

    2010-01-01

    This paper presents a new state-space approach for temporal analysis of electrical circuits. The method systematically obtains the state-space formulation of nondegenerate linear networks without using concepts of topology. It employs nodal/mesh systematic analysis to reduce the number of undesired variables. This approach helps students to…

  20. Formulation of statistical mechanics for chaotic systems

    Indian Academy of Sciences (India)

    Here, we again strengthen the idea of statistical mechanics of chaotic systems using Kinchin's formulation based on microcanonical ensemble [13]. Further, we extend the study to canonical ensemble of such a system and as an example, we consider QO and obtain various thermodynamic quantities and the results are.

  1. Development and Evaluation of Topical Gabapentin Formulations

    Directory of Open Access Journals (Sweden)

    Christopher J. Martin

    2017-08-01

    Full Text Available Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w gabapentin 0.75% (w/w Carbopol® hydrogels containing 5% (w/w DMSO or 70% (w/w ethanol and a compounded 10% (w/w gabapentin Lipoderm® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations.

  2. Development and Evaluation of Topical Gabapentin Formulations

    Science.gov (United States)

    Alcock, Natalie; Hiom, Sarah; Birchall, James C.

    2017-01-01

    Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w) gabapentin 0.75% (w/w) Carbopol® hydrogels containing 5% (w/w) DMSO or 70% (w/w) ethanol and a compounded 10% (w/w) gabapentin Lipoderm® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations. PMID:28867811

  3. Kit systems for granulated decontamination formulations

    Science.gov (United States)

    Tucker, Mark D.

    2010-07-06

    A decontamination formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a sorbent additive, and water. A highly adsorbent sorbent additive (e.g., amorphous silica, sorbitol, mannitol, etc.) is used to "dry out" one or more liquid ingredients into a dry, free-flowing powder that has an extended shelf life, and is more convenient to handle and mix in the field. The formulation can be pre-mixed and pre-packaged as a multi-part kit system, where one or more of the parts are packaged in a powdered, granulated form for ease of handling and mixing in the field.

  4. Formulation of Sodium Alginate Nanospheres Containing ...

    African Journals Online (AJOL)

    Purpose: The aim of this work was to formulate sodium alginate nanospheres of amphotericin B by controlled gellification method and to evaluate the role of the nanospheres as a “passive carrier” in targeted antifungal therapy. Methods: Sodium alginate nanospheres of amphotericin B were prepared by controlled ...

  5. Compounded laxative formulations for substituting phenolphthalein ...

    African Journals Online (AJOL)

    Dr Patrick O Erah

    acid, PEG, and sugar derivatives such as lactose, glucose and sorbitol when granulated with water. Not withstanding these interactions, it was possible to compound simple capsule, tablet and even an effervescent tablet formulations containing sennosides A & B that complied with pharmacopeial specifications. However ...

  6. Formulation of Thermosensitive Hydrogel Containing Cyclodextrin ...

    African Journals Online (AJOL)

    Formulation of Thermosensitive Hydrogel Containing Cyclodextrin for Controlled Drug Delivery of Camptothecin. ... Camptothecin (CPT) released from the hydrogel (TF8) over 8 h in pH 7.4 buffer ranged from 38.97 - 92.5 %, and varied according to the composition of the hydrogels. Release of camptothecin was lowest from ...

  7. Screening of mucoadhesive vaginal gel formulations

    Directory of Open Access Journals (Sweden)

    Ana Ochoa Andrade

    2014-12-01

    Full Text Available Rational design of vaginal drug delivery formulations requires special attention to vehicle properties that optimize vaginal coating and retention. The aim of the present work was to perform a screening of mucoadhesive vaginal gels formulated with carbomer or carrageenan in binary combination with a second polymer (carbomer, guar or xanthan gum. The gels were characterised using in vitroadhesion, spreadability and leakage potential studies, as well as rheological measurements (stress and frequency sweep tests and the effect of dilution with simulated vaginal fluid (SVF on spreadability. Results were analysed using analysis of variance and multiple factor analysis. The combination of polymers enhanced adhesion of both primary gelling agents, carbomer and carrageenan. From the rheological point of view all formulations presented a similar behaviour, prevalently elastic and characterised by loss tangent values well below 1. No correlation between rheological and adhesion behaviour was found. Carbomer and carrageenan gels containing the highest percentage of xanthan gum displayed good in vitro mucoadhesion and spreadability, minimal leakage potential and high resistance to dilution. The positive results obtained with carrageenan-xanthan gum-based gels can encourage the use of natural biocompatible adjuvants in the composition of vaginal products, a formulation field that is currently under the synthetic domain.

  8. Comparative evaluation of organic formulations of Pseudomonas ...

    African Journals Online (AJOL)

    Comparative evaluation of organic formulations of Pseudomonas fluorescens based biopesticides and their application in the management of bacterial wilt of brinjal ... Effective management of bacterial wilt of brinjal by P. fluorescens under local conditions signifies its potentiality and scope as a plant growth promoting ...

  9. [Optimization of formulations for dietetic pastry products].

    Science.gov (United States)

    Villarroel, M; Uquiche, E; Brito, G; Cancino, M

    2000-03-01

    Optimized formulations of dietetic pastry products such as cake and sponge cake premixes were formulated using the surface response methodology. % Emulsifier agent and baking time were the selected independent variables for cake, as well as % emulsifier agent % chlorinated flour the variables selected for sponge cake. Three different level of each variable summing up thirteen experimental formulae of each product were assessed to optimize the variables that could have some influence in the sensory characteristics of these dietetic products. The total sensory quality was determined for both dietetic products using the composite scoring test and a panel of 18 trained judges. Looking at the contour graphic and considering economic aspects the best combination of variables for cake formulation was 2% emulsifier agent and 48 minutes for baking time, With respect to sponge cake, the best combination was 6% emulsifier agent and 48% chlorinated flour. Shelf life studies showed that both dietetic formulations remained stable during storage conditions of 75 days at 30 degrees C. During this period, significant differences in sensory characteristics were not found (p pastry products had good acceptability, and open up marketing opportunities for new products with potential health benefits to consumers.

  10. Release Properties of Paracetamol Granulationa Formulated with ...

    African Journals Online (AJOL)

    Theobroma cacao gum, TCG was derived as a dry powder from fresh fruits of Theobroma cacao. Various granulations of paracetamol were prepared with TCG at the concentrations of 0.5 – 4% w/w. Similar formulations were prepared using sodium carboxymethyl cellulose, SCMC and acacia gums as standards. In each ...

  11. Hepatoprotective activity of polyherbal formulation against carbon ...

    African Journals Online (AJOL)

    hope&shola

    2010-12-06

    Dec 6, 2010 ... The ethanloic extracts of the polyherbal medicinal plants (Asteracantha longifolia, Cyperus rotundus and Bryophyllum pinnatum) were evaluated for hepatoprotective activity in carbon tetrachloride induced liver damage in rats. The ethanolic extract of polyherbal formulation at 250 mg/kg b.w. exhibited a ...

  12. Initial value formulation of higher derivative gravity

    International Nuclear Information System (INIS)

    Noakes, D.R.

    1983-01-01

    The initial value problem is considered for the conformally coupled scalar field and higher derivative gravity, by expressing the equations of each theory in harmonic coordinates. For each theory it is shown that the (vacuum) equations can take the form of a diagonal hyperbolic system with constraints on the initial data. Consequently these theories possess well-posed initial value formulations

  13. Formulation of statistical mechanics for chaotic systems

    Indian Academy of Sciences (India)

    We formulate the statistical mechanics of chaotic system with few degrees of freedom and investigated the quartic oscillator system using microcanonical and canonical ensembles. Results of statistical mechanics are numerically verified by considering the dynamical evolution of quartic oscillator system with two degrees of ...

  14. On fictitious domain formulations for Maxwell's equations

    DEFF Research Database (Denmark)

    Dahmen, W.; Jensen, Torben Klint; Urban, K.

    2003-01-01

    We consider fictitious domain-Lagrange multiplier formulations for variational problems in the space H(curl: Omega) derived from Maxwell's equations. Boundary conditions and the divergence constraint are imposed weakly by using Lagrange multipliers. Both the time dependent and time harmonic...

  15. Efficacy of Three Disinfectant Formulations against Multidrug ...

    African Journals Online (AJOL)

    The current increase in the prevalence of nosocomial infections within the hospital environment despite adequate cleaning and disinfection can be said to be due to the following: (i) ineffectiveness of the various disinfectant formulations used in infection control on the various hospital equipments and wards; (ii) development ...

  16. PERFORMANCE OF LOCALLY FORMULATED FEEDS FOR ...

    African Journals Online (AJOL)

    ACSS

    Fisheries is an important food production sub-sector, providing almost 20% of the world's protein supply; however, the trend in fish production from capture fisheries has reached its limits due to overfishing. A study was conducted to evaluate the performance of two locally formulated feeds as possible replacements for an ...

  17. Formulation and Characterization of Biodegradable Medicated ...

    African Journals Online (AJOL)

    (TPA), biodegradation, in vitro drug release using a modified chewing apparatus, and sensory properties. Result: Formulations code MCG-5 and MCG-9 which incorporated glyceryl triacetate and castor oil as plasticizers, respectively, showed a biodegradation score of 2 and 1, respectively, indicating significant.

  18. Formulation of Bioadhesive Carbomer Gel Incorporating Drug ...

    African Journals Online (AJOL)

    Purpose: To formulate carbomer gel to localize and target drug action in periodontal pockets. Methods: Diclofenac sodium (DS, anti-inflammatory) and metronidazole hydrochloride (MH, antibacterial) were loaded in gelatin microspheres using glutaraldehyde cross-linking. The microspheres were evaluated for drug loading, ...

  19. A parcel formulation for Hamiltonian layer models

    NARCIS (Netherlands)

    Bokhove, Onno; Oliver, M.

    Starting from the three-dimensional hydrostatic primitive equations, we derive Hamiltonian N-layer models with isentropic tropospheric and isentropic or isothermal stratospheric layers. Our construction employs a new parcel Hamiltonian formulation which describes the fluid as a continuum of

  20. Application of UV Imaging in Formulation Development.

    Science.gov (United States)

    Sun, Yu; Østergaard, Jesper

    2017-05-01

    Efficient drug delivery is dependent on the drug substance dissolving in the body fluids, being released from dosage forms and transported to the site of action. A fundamental understanding of the interplay between the physicochemical properties of the active compound and pharmaceutical excipients defining formulation behavior after exposure to the aqueous environments and pharmaceutical performance is critical in pharmaceutical development, manufacturing and quality control of drugs. UV imaging has been explored as a tool for qualitative and quantitative characterization of drug dissolution and release with the characteristic feature of providing real-time visualization of the solution phase drug transport in the vicinity of the formulation. Events occurring during drug dissolution and release, such as polymer swelling, drug precipitation/recrystallization, or solvent-mediated phase transitions related to the structural properties of the drug substance or formulation can be monitored. UV imaging is a non-intrusive and simple-to-operate analytical technique which holds potential for providing a mechanistic foundation for formulation development. This review aims to cover applications of UV imaging in the early and late phase pharmaceutical development with a special focus on the relation between structural properties and performance. Potential areas of future advancement and application are also discussed.

  1. Formulation and Release Characteristics of Zidovudine- Loaded ...

    African Journals Online (AJOL)

    novel microencapsulating material for ibuprofen and diltiazem hydrochloride. Indian J. Pharm. Sci. 2007; 67: 263–268. 15. Doktorovova S, Souto EB. Nanostructured lipid carrier- based hydrogel formulations for drug delivery: A comprehensive review. Expert Opin Drug Deliv. 2009; 6: 165–176. 16. Higuchi T. Mechanism of ...

  2. Necessity of rethinking oral pediatric formulations

    DEFF Research Database (Denmark)

    Bar-Shalom, Daniel

    2014-01-01

    by all patient groups, is needed, and an automated compounding concept is proposed. The finishing of the formulation is done at the dispensing pharmacy using an automated process. The individual components (pudding-like carrier, microencapsulated drug, and the dispensing robot and its software...

  3. Mathematical programming formulations for the examinations ...

    African Journals Online (AJOL)

    We formulate, test and compare three Integer Programming models. It is concluded that, although exact methods cannot give a solution to a real-size problem, these models give a good benchmark for testing the performance of other approaches. This paper also gives a direction for better exact models for the University of ...

  4. Potentials of cellulosic wastes in media formulation

    African Journals Online (AJOL)

    AJB SERVER

    2007-02-05

    Feb 5, 2007 ... Potential use of cellulosic wastes as carbon and energy sources in selective media formulations was investigated. Two agar media, Czapek-Dox and Sabouraud's agar, were modified by substituting their carbon sources with cellulose, sawdust and sugarcane pulps. Then, two fungi; Aspergillus niger.

  5. Lipid nanoparticles based on butyl-methoxydibenzoylmethane: in vitro UVA blocking effect

    International Nuclear Information System (INIS)

    Niculae, G; Lacatusu, I; Badea, N; Meghea, A

    2012-01-01

    The aim of the present study was to obtain efficient lipid nanoparticles loaded with butyl-methoxydibenzoylmethane (BMDBM) in order to develop cosmetic formulations with enhanced UVA blocking effect. For this purpose, two adequate liquid lipids (medium chain triglycerides and squalene) have been used in combination with two solid lipids (cetyl palmitate and glyceryl stearate) in order to create appropriate nanostructured carriers with a disordered lipid network able to accommodate up to 1.5% BMDBM. The lipid nanoparticles (LNs) were characterized in terms of particle size, zeta potential, entrapment efficiency, loading capacity and in vitro UVA blocking effect. The efficiency of lipid nanoparticles in developing some cosmetic formulations has been evaluated by determining the in vitro erythemal UVA protection factor. In order to quantify the photoprotective effect, some selected cream formulations based on BMDBM-LNs and a conventional emulsion were exposed to photochemical UV irradiation at a low energy to simulate the solar energy during the midday. The results obtained demonstrated the high ability of cream formulations based on BMDBM-LNs to absorb more than 96% of UVA radiation. Moreover, the developed cosmetic formulations manifest an enhanced UVA blocking effect, the erythemal UVA protection factor being four times higher than those specific to conventional emulsions. (paper)

  6. Human in vivo and in vitro studies on gastrointestinal absorption of titanium dioxide nanoparticles.

    Science.gov (United States)

    Jones, Kate; Morton, Jackie; Smith, Ian; Jurkschat, Kerstin; Harding, Anne-Helen; Evans, Gareth

    2015-03-04

    The study was designed to conduct human in vivo and in vitro studies on the gastrointestinal absorption of nanoparticles, using titanium dioxide as a model compound, and to compare nanoparticle behaviour with that of larger particles. A supplier's characterisation data may not fully describe a particle formulation. Most particles tested agreed with their supplied characterisation when assessed by particle number but significant proportions of 'nanoparticle formulations' were particles >100nm when assessed by particle weight. Oral doses are measured by weight and it is therefore important that the weight characterisation is taken into consideration. The human volunteer studies demonstrated that very little titanium dioxide is absorbed gastrointestinally after an oral challenge. There was no demonstrable difference in absorption for any of the three particle sizes tested. All tested formulations were shown to agglomerate in simulated gastric fluid, particularly in the smaller particle formulations. Further agglomeration was observed when dispersing formulations in polymeric or elemental foods. Virtually no translocation of titanium dioxide particles across the cell layer was demonstrated. This study found no evidence that nanoparticulate titanium dioxide is more likely to be absorbed in the gut than micron-sized particles. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Silica nanoparticle coated liposomes: a new type of hybrid nanocapsule for proteins.

    Science.gov (United States)

    Mohanraj, Vellore J; Barnes, Timothy J; Prestidge, Clive A

    2010-06-15

    A hybrid silica-liposome nanocapsule system containing insulin has been developed and the encapsulation, protection and release properties are evaluated. The formulation strategy is based on using insulin-loaded 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and cholesterol liposomes as a template for the deposition of inert silica nanoparticles. The influence of formulation and process variables on particle size, zeta potential and liposome entrapment of insulin is reported. The ability to protect against lipolytic degradation and sustain insulin release in vitro in simulated GI conditions is also reported. Depending on the concentration and charge ratio of liposomes and silica nanoparticles, nanoparticle coated liposomes with varied size and zeta potential were obtained with an insulin entrapment efficiency of 70%. The silica nanoparticle coating protected liposomes against degradation by digestive enzymes in vitro; the release rate of insulin from silica coated liposomes was reduced in comparison to uncoated liposomes. Thus the liposomal release kinetics and stability can be controlled by including a specifically engineered nanoparticle layer. Silica nanoparticle-liposomes hybrid nanocapsules show promise as a delivery vehicle for proteins and peptides. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

  8. Evaluation of Organogel Nanoparticles as Drug Delivery System for Lipophilic Compounds.

    Science.gov (United States)

    Martin, Baptiste; Brouillet, Fabien; Franceschi, Sophie; Perez, Emile

    2017-05-01

    The purpose of the study was to evaluate organogel nanoparticles as a drug delivery system by investigating their stability, according to the formulation strategy, and their release profile. The gelled nanoparticles were prepared by hot emulsification (above the gelation temperature) of an organogel in water, and cooling at room temperature. In the first step, we used DLS and DSC to select the most suitable formulations by optimizing the proportion of ingredients (HSA, PVA, castor oil) to obtain particles of the smallest size and greatest stability. Then, two lipophilic drug models, indomethacin and ketoconazole were entrapped in the nanoparticles made of castor oil gelled by 12-hydroxystearic acid. Thermal studies (DSC) confirmed that there was no significant alteration of gelling due to the entrapped drugs, even at 3% w/w. Very stable dispersions were obtained (>3 months), with gelled oil nanoparticles presenting a mean diameter between 250 and 300 nm. High encapsulation efficiency (>98%) was measured for indomethacin and ketoconazole. The release profile determined by in vitro dialysis showed an immediate release of the drug from the organogel nanoparticles, due to rapid diffusion. The study demonstrates the interest of these gelled oil nanoparticles for the encapsulation and the delivery of lipophilic active compounds.

  9. EGFR-targeted gelatin nanoparticles for systemic administration of gemcitabine in an orthotopic pancreatic cancer model.

    Science.gov (United States)

    Singh, Amit; Xu, Jing; Mattheolabakis, George; Amiji, Mansoor

    2016-04-01

    In this study, we have formulated redox-responsive epidermal growth factor receptor (EGFR)-targeted type B gelatin nanoparticles as a targeted vector for systemic delivery of gemcitabine therapy in pancreatic cancer. The gelatin nanoparticles were formed by ethanol-induced desolvation process to encapsulate the bound drug. The surface of the nanoparticles was decorated either with poly(ethylene glycol) (PEG) chains to impart enhanced circulation time or with EGFR targeting peptide to confer target specificity. Our in vitro studies in Panc-1 human pancreatic ductal adenocarcinoma cells confirm that gemcitabine encapsulated in EGFR-targeted gelatin nanoparticles, released through disulfide bond cleavage, had a significantly improved cytotoxic profile. Further, the in vivo anticancer activity was evaluated in an orthotopic pancreatic adenocarcinoma tumor bearing SCID beige mice, which confirmed that EGFR-targeted gelatin nanoparticles could efficiently deliver gemcitabine to the tumor leading to higher therapeutic benefit as compared to the drug in solution. The treatment of pancreatic cancer remains unsatisfactory, with an average 5-year survival of less than 5%. New treatment modalities are thus urgently needed. In this study, the authors presented their formulation of redox-responsive epidermal growth factor receptor (EGFR)-targeted type B gelatin nanoparticles as a carrier for gemcitabine. In-vitro and in-vivo experiments showed encouraging results. It is hoped that the findings would provide a novel and alternative drug delivery platform for the future. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Design of a dual nanostructured lipid carrier formulation based on physicochemical, rheological, and mechanical properties

    Energy Technology Data Exchange (ETDEWEB)

    Vitorino, Carla [University of Coimbra, Centro de Estudos Farmaceuticos (CEF), Faculty of Pharmacy (Portugal); Alves, Luis; Antunes, Filipe E. [University of Coimbra, Department of Chemistry (Portugal); Sousa, Joao J. [University of Coimbra, Centro de Estudos Farmaceuticos (CEF), Faculty of Pharmacy (Portugal); Pais, Alberto A. C. C., E-mail: pais@qui.uc.pt [University of Coimbra, Department of Chemistry (Portugal)

    2013-10-15

    The synergy between nanostructured lipid carriers (NLC) and chemical penetration enhancers provides the basis for a promising strategy to effectively deliver drugs through the skin. In the present work, focus is given to the study of the interaction of limonene, ethanol, and Carbopol Ultrez{sup Registered-Sign} 10NF, as the gelling agent, with a co-encapsulating NLC dispersion, containing both olanzapine and simvastatin. The analysis is based on rheological, mechanical, and physicochemical properties. The nanoparticle size ranged from 130 to 400 nm, depending on the system considered. The inclusion of carbopol resulted in a considerable increase in the NLC particle size, which was attributed to carbomer bridging nanoparticles, resulting in some particle aggregation. Rheological measurements indicated that the viscosity of the neat carbopol hydrogel was reduced by the enhancers and to a higher extent by the presence of NLC. A more apolar medium can be pointed out as a general explanation, while a polymer/nanoparticle hydrophobic interaction coupled with surfactant/polymer H-bonding provides the rationale for the NLC effect. The inclusion of enhancers and a carbomer largely contributed to the physicochemical stability of the NLC formulation, as revealed by the low transmission profiles and more negative zeta potential values.

  11. Formulation and in vitro evaluation of highly dispersive insulin dry powder formulations for lung administration.

    Science.gov (United States)

    Depreter, Flore; Amighi, Karim

    2010-11-01

    The aim of this work was to develop highly dispersible and dry formulations of insulin for use in dry powder inhalers (DPIs) using high-pressure homogenisation (HPH) and spray-drying. Several formulations were evaluated, including formulations spray-dried without excipients and formulations coated with lipids. A physiological lipid composition based on a mixture of cholesterol and phospholipids was used to form the coating film around micronised drug particles. The production technique and excipients were chosen in order to limit the degradation of the active ingredient. The resulting powders exhibited a size and shape suitable for the deep lung deposition of drugs, and good aerodynamic features were obtained for the different formulations tested, with fine particle fractions between 46% and 63% vs. 11% for raw insulin powder. The presence of a lipid coating of up to 30% (w/w) did not significantly affect the aerodynamic behaviour, and the coated formulations also exhibited a decreased residual moisture content of between 2.3% and 3.7% vs. 4.8% for raw insulin, which should improve the long-term stability of the protein formulations. No degradation of the insulin molecule occurred during the HPH/spray-drying process, as it was shown using an HPLC method (insulin content between 98.4% and 100.5%), and the content in high molecular weight proteins, assessed using a gel filtration method, stayed below 0.4%. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Synthesis and characterization of folate decorated albumin bio-conjugate nanoparticles loaded with a synthetic curcumin difluorinated analogue.

    Science.gov (United States)

    Gawde, Kaustubh A; Kesharwani, Prashant; Sau, Samaresh; Sarkar, Fazlul H; Padhye, Subhash; Kashaw, Sushil K; Iyer, Arun K

    2017-06-15

    Albumin-bound paclitaxel colloidal nanoparticle (Abraxane®) is an FDA approved anticancer formulation available in the market. It is a suspension which is currently used therapeutically for treating cancers of the breast, lung, and pancreas among others. CDF is a novel new and potent synthetic curcumin analogue that is widely used for breast and ovarian cancer. The aim of this study was to use biocompatible albumin as well as folate decorated albumin to formulate colloidal nanoparticles encapsulating curcumin difluorinated (CDF). CDF has demonstrated a 16-fold improvement in stability and remarkable anticancer potency compared to its natural derivative, curcumin. CDF showed marked inhibition of cancer cell growth through down-regulation of multiple miRNAs, up-regulation of phosphatase and tensin homolog (PTEN), and attenuation of histone methyl transferase EZH2. However, CDF is highly hydrophobic and photodegradable with sparing aqueous solubility. In this study, we have formulated albumin nanoparticle using a modified desolvation method, which yielded high CDF loading in a nanoformulation. The physicochemical properties of CDF loaded albumin and folate-decorated albumin nanosuspensions were assessed for particle size, morphology, zeta potential, drug encapsulation efficiency/loading, solubility and drug release. Importantly, the folate ligand decorated albumin nanoparticles were formulated in principle to passively and actively target folate-overexpressing-cancers. In this study, the synthesis and optimization of BSA and folate decorated BSA conjugated CDF nanoparticles are assessed in detail that will be useful for its future clinical translation. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Effects of 14-day oral low dose selenium nanoparticles and selenite in rat—as determined by metabolite pattern determination

    DEFF Research Database (Denmark)

    Hadrup, Niels; Löschner, Katrin; Skov, Kasper

    2016-01-01

    toxic effects may occur. We used metabolite pattern determination in urine to investigate biological and/or toxic effects in rats administered nanoparticles and for comparison included ionic selenium at an equimolar dose in the form of sodium selenite. Low doses of 10 and 100 fold the recommended human......Selenium (Se) is an essential element with a small difference between physiological and toxic doses. To provide more effective and safe Se dosing regimens, as compared to dosing with ionic selenium, nanoparticle formulations have been developed. However, due to the nano-formulation, unexpected...

  14. Repairing Nanoparticle Surface Defects

    NARCIS (Netherlands)

    Marino, Emanuele; Kodger, Thomas E.; Crisp, R.W.; Timmerman, Dolf; MacArthur, Katherine E.; Heggen, Marc; Schall, Peter

    2017-01-01

    Solar devices based on semiconductor nanoparticles require the use of conductive ligands; however, replacing the native, insulating ligands with conductive metal chalcogenide complexes introduces structural defects within the crystalline nanostructure that act as traps for charge carriers. We

  15. Functionalized diamond nanoparticles

    KAUST Repository

    Beaujuge, Pierre M.

    2014-10-21

    A diamond nanoparticle can be functionalized with a substituted dienophile under ambient conditions, and in the absence of catalysts or additional reagents. The functionalization is thought to proceed through an addition reaction.

  16. Metallic Magnetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    A. Hernando

    2005-01-01

    Full Text Available In this paper, we reviewed some relevant aspects of the magnetic properties of metallic nanoparticles with small size (below 4 nm, covering the size effects in nanoparticles of magnetic materials, as well as the appearance of magnetism at the nanoscale in materials that are nonferromagnetic in bulk. These results are distributed along the text that has been organized around three important items: fundamental magnetic properties, different fabrication procedures, and characterization techniques. A general introduction and some experimental results recently obtained in Pd and Au nanoparticles have also been included. Finally, the more promising applications of magnetic nanoparticles in biomedicine are indicated. Special care was taken to complete the literature available on the subject.

  17. Evaluation of the cytotoxic and inflammatory potential of differentially shaped zinc oxide nanoparticles.

    Science.gov (United States)

    Heng, Boon Chin; Zhao, Xinxin; Tan, Eng Chok; Khamis, Nurulain; Assodani, Aarti; Xiong, Sijing; Ruedl, Christiane; Ng, Kee Woei; Loo, Joachim Say-Chye

    2011-12-01

    Zinc oxide (ZnO) nanoparticles have wide-ranging applications in a diverse array of industrial and consumer products, from ceramic manufacture and paint formulation to sunscreens and haircare products. Hence, it is imperative to rigorously characterize the health and safety aspects of human exposure to ZnO nanoparticles. This study therefore evaluated the cellular association, cytotoxic and inflammatory potential of spherical and sheet-shaped ZnO nanoparticles (of approximately the same specific surface area ≈30 cm²/g) on mouse and human cell lines (RAW-264.7 and BEAS-2B respectively), as well as with primary cultures of mouse bone marrow-derived dendritic cells (DC). The WST-8 assay demonstrated dose-dependent effects on the cytotoxicity of spherical and sheet-shaped ZnO nanoparticles on both RAW-264.7 and BEAS-2B cells, even though there was no significant effect of shape on the cytotoxicity of ZnO nanoparticles. There was however higher cellular association of spherical versus sheet-shaped ZnO nanoparticles. Measurement of reactive oxygen species (ROS) with the 2',7'-dichlorfluorescein-diacetate (DCFH-DA) assay indicated up to 4-folds increase in ROS level upon exposure to ZnO nanoparticles, but there was again no significant difference between both ZnO nanoparticle shapes. Exposure of primary dendritic cells to ZnO nanoparticles upregulated expression of CD80 and CD86 (well-known markers of DC activation and maturation) and stimulated release of pro-inflammatory cytokines--IL-6 and TNF-α, thus pointing to the potential of ZnO nanoparticles in inducing inflammation. Hence, our study indicated that ZnO nanoparticles can have potential detrimental effects on cells even at dosages where there are little or no observable cytotoxic effects.

  18. Characterization of polymer adsorption onto drug nanoparticles using depletion measurements and small-angle neutron scattering.

    Science.gov (United States)

    Goodwin, Daniel J; Sepassi, Shadi; King, Stephen M; Holland, Simon J; Martini, Luigi G; Lawrence, M Jayne

    2013-11-04

    Production of polymer and/or surfactant-coated crystalline nanoparticles of water-insoluble drugs (nanosuspensions) using wet bead milling is an important formulation approach to improve the bioavailability of said compounds. Despite the fact that there are a number of nanosuspensions on the market, there is still a deficiency in the characterization of these nanoparticles where further understanding may lead to the rational selection of polymer/surfactant. To this end small-angle neutron scattering (SANS) measurements were performed on drug nanoparticles milled in the presence of a range of polymers of varying molecular weight. Isotopic substitution of the aqueous solvent to match the scattering length density of the drug nanoparticles (i.e., the technique of contrast matching) meant that neutron scattering resulted only from the adsorbed polymer layer. The layer thickness and amount of hydroxypropylcellulose adsorbed on nabumetone nanoparticles derived from fitting the SANS data to both model-independent and model dependent volume fraction profiles were insensitive to polymer molecular weight over the range Mv = 47-112 kg/mol, indicating that the adsorbed layer is relatively flat but with tails extending up to approximately 23 nm. The constancy of the absorbed amount is in agreement with the adsorption isotherm determined by measuring polymer depletion from solution in the presence of the nanoparticles. Insensitivity to polymer molecular weight was similarly determined using SANS measurements of nabumetone or halofantrine nanoparticles stabilized with hydroxypropylmethylcellulose or poly(vinylpyrrolidone). Additionally SANS studies revealed the amount adsorbed, and the thickness of the polymer layer was dependent on both the nature of the polymer and drug particle surface. The insensitivity of the adsorbed polymer layer to polymer molecular weight has important implications for the production of nanoparticles, suggesting that lower molecular weight polymers

  19. Ocular Disposition of ∆8-Tetrahydrocannabinol from Various Topical Ophthalmic Formulations.

    Science.gov (United States)

    Punyamurthula, Nagendra S; Adelli, Goutham R; Gul, Waseem; Repka, Michael A; ElSohly, Mahmoud A; Majumdar, Soumyajit

    2017-08-01

    The purposes of this project are to enhance the trans-membrane penetration of Δ 8 -Tetrahydrocannabinol (Δ 8 -THC) and to study the effect of various lipid based systems in delivering the compound, non-invasively, to anterior and posterior ocular chambers. Solid lipid nanoparticles (SLNs), fast gelling films were manufactured using high pressure homogenization and melt cast techniques, respectively. The formulations were characterized for drug content, entrapment efficiency, particle size and subsequently evaluated in vitro for trans-corneal permeation. In vivo, the drug disposition was tested via topical administration in albino rabbits. The eye globes were enucleated at the end of experiment and tissues were analyzed for drug content. All formulations showed favorable physicochemical characteristics in terms of particle size, entrapment efficiency, and drug content. In vitro, the formulations exhibited a transcorneal flux that depended on the formulation's drug load. An increase in drug load from 0.1 to 0.75% resulted in 12- to16-folds increase in permeation. In vivo, the film was able to deliver THC to all the tissues with high accumulations in cornea and sclera. The SLNs showed a greater ability in delivering THC to all the tissues, at a significantly lower drug load, due to their colloidal size range, which in turn enhanced corneal epithelial membrane penetration. The topical formulations evaluated in the present study were able to successfully deliver Δ 8 -THC in therapeutically meaningful concentrations (EC 50 values for CB 1 : 6 nM and CB 2 : 0.4 nM) to all ocular tissues except the vitreous humor, with pronounced tissue penetration achieved using SLNs as a Δ 8 -THC delivery vehicle.

  20. Transport and Development of Microemulsionand Surfactant Stabilized Iron Nanoparticles for In Situ Remediation

    Science.gov (United States)

    Hsu, Dennis

    This work describes the mobility assessments of microemulsion-stabilized iron oxide nanoparticles and anionic surfactant sodium diethyl hexyl phosphate (SDEHP)-stabilized nanoscale zero valent iron (NZVI) particles in laboratory porous media. The two formulations tested in this work achieved stable iron nanoparticle suspensions for months and prepared via a simple "one-pot" synthesis method developed by Wang et al. Both formulations were tested under field scale velocity of 5 m/day with no mechanical aid during the injection. A three-compartment model, involving colloid diffusion theory, diffusion theory and tailing was applied to describe the breakthrough curves of the studies. The obtained breakthrough curves of both formulations implied excellent transport in porous media with steady plateau C/Co at 0.8-0.9 and recovery of up to 0.95 for SDEHP stabilized NZVI. Post analysis on the retention of iron on the porous media implied ideal transport with consistent data to the breakthrough curves.

  1. Biomimetic magnetic nanoparticles

    OpenAIRE

    Klem, Michael T.; Young, Mark; Douglas, Trevor

    2005-01-01

    Magnetic nanoparticles are of considerable interest because of their potential use in high-density memory devices, spintronics, and applications in diagnostic medicine. The conditions for synthesis of these materials are often complicated by their high reaction temperatures, costly reagents, and post-processing requirements. Practical applications of magnetic nanoparticles will require the development of alternate synthetic strategies that can overcome these impediments. Biomimetic approaches...

  2. Nanolubricant: magnetic nanoparticle based

    Science.gov (United States)

    Trivedi, Kinjal; Parekh, Kinnari; Upadhyay, Ramesh V.

    2017-11-01

    In the present study magnetic nanoparticles of Fe3O4 having average particle diameter, 11.7 nm were synthesized using chemical coprecipitation technique and dispersed in alpha olefin hydrocarbon synthetic lubricating oil. The solid weight fraction of magnetic nanoparticles in the lubricating oil was varied from 0 wt% to 10 wt%. The tribological properties were studied using four-ball tester. The results demonstrate that the coefficient of friction and wear scar diameter reduces by 45% and 30%, respectively at an optimal value, i.e. 4 wt% of magnetic nanoparticles concentration. The surface characterization of worn surface was carried out using a scanning electron microscope, and energy dispersive spectroscopy. These results implied that rolling mechanism is responsible to reduce coefficient of friction while magnetic nanoparticles act as the spacer between the asperities and reduces the wear scar diameter. The surface roughness of the worn surface studied using an atomic force microscope shows a reduction in surface roughness by a factor of four when magnetic nanoparticles are used as an additive. The positive response of magnetic nanoparticles in a lubricating oil, shows the potential replacement of conventional lubricating oil.

  3. Protein trapping of nanoparticles

    International Nuclear Information System (INIS)

    Ang, Joo C.; Lin, Jack M.; Yaron, Peter N.; White, John W.

    2009-01-01

    Full text: We have observed the formation of protein-nanoparticle complexes at the air-water interfaces from three different methods of presenting the nanoparticles to proteins. The structures formed resemble the 'protein-nanoparticle corona' proposed by Lynch et al. [1-3) in relation to a possible route for nanoparticle entry into living cells. To do this, the methods of x-ray and neutron reflectivity (with isotopic contrast variation between the protein and nanoparticles) have been used to study the structures formed at the air-water interface of l 3 - casein presented to silica nanoparticle dispersions. Whilst the silica dispersions showed no observable reflectivity, strong signals appear in the reflectivity when protein is present. Drop-wise spreading of a small amount of protein at the air-silica sol interface and presentation of the silica sol to an isolated monomolecular protein film (made by the 'flow-trough' method [4]) gave an immediate signal. Mixing the components in solution only produces a slow response but in all cases a similar structure is formed. The different responses are interpreted in structural and stoichiometric ways.

  4. Flexible continuous manufacturing platforms for solid dispersion formulations

    Science.gov (United States)

    Karry-Rivera, Krizia Marie

    In 2013 16,000 people died in the US due to overdose from prescription drugs and synthetic narcotics. As of that same year, 90% of new molecular entities in the pharmaceutical drug pipeline are classified as poor water-soluble. The work in this dissertation aims to design, develop and validate platforms that solubilize weak acids and can potentially deter drug abuse. These platforms are based on processing solid dispersions via solvent-casting and hot-melt extrusion methods to produce oral transmucosal films and melt tablets. To develop these platforms, nanocrystalline suspensions and glassy solutions were solvent-casted in the form of films after physicochemical characterizations of drug-excipient interactions and design of experiment approaches. A second order model was fitted to the emulsion diffusion process to predict average nanoparticle size and for process optimization. To further validate the manufacturing flexibility of the formulations, glassy solutions were also extruded and molded into tablets. This process included a systematic quality-by-design (QbD) approach that served to identify the factors affecting the critical quality attributes (CQAs) of the melt tablets. These products, due to their novelty, lack discriminatory performance tests that serve as predictors to their compliance and stability. Consequently, Process Analytical Technology (PAT) tools were integrated into the continuous manufacturing platform for films. Near-infrared (NIR) spectroscopy, including chemical imaging, combined with deconvolution algorithms were utilized for a holistic assessment of the effect of formulation and process variables on the product's CQAs. Biorelevant dissolution protocols were then established to improve the in-vivo in-vitro correlation of the oral transmucosal films. In conclusion, the work in this dissertation supports the delivery of poor-water soluble drugs in products that may deter abuse. Drug nanocrystals ensured high bioavailability, while glassy

  5. Formulation of Pine Tar Antidandruff Shampoo Assessment and Comparison With Some Commercial Formulations

    Directory of Open Access Journals (Sweden)

    M. Gharavi

    1990-07-01

    Full Text Available In this study a pine tar shampoo as a new antidandruff formulation is presented. Assessment of antidandruff preparations has been hampered by the lack of standardized schedules, and reliable methods of evaluation.Some antidandruff agents such as : Zinc pyri-thione pine tar, selenium sulphide and (sulfure were used in shampoos. Samples were coded as numbers 1,2 formulated by us and 3,4 formulated commercially. The grading scheme based on 10 point scale, and corneocyte count was carried out on 50 selected volunte¬ers. Corneocyte count and fungal study proved that pine tor shampoo is effective against pityrosporum ovale. Draize lest was used for determination of the irritancy potential of the samples. Results showed that samples numbered 1,2 were relatively innocous in comparison with the others. I urthermore,s kin sensitination test on rabbit also confirmed the results obtained by Draize test. Consumer judgments proved that all formulations were acceptable.

  6. Fast switching of frequency modulation twisted nematic liquid crystal display fabricated by doping nanoparticles and its mechanism (Invited Paper)

    Science.gov (United States)

    Kobayashi, Shunsuke; Miyama, Tomohiro; Sakai, Yoshio; Shiraki, Hiroyuki; Shiraishi, Yukihide; Toshima, Naoki

    2005-04-01

    TN-LCDs fabricated by doping metal nanoparticles of such as Pd, Ag, Au, or Ag-Pd composite are shown to exhibit a frequency modulation electro-optic response with short response time of ms or sub-ms order. These devices are called FM-LCDs. The frequency range spreads from 40 Hz to 2 KHz around a dielectric relaxation frequency that increases with increasing the concentration of metal nanoparticles. This behavior is explained by the equivalent circuit model of heterogeneous dielectrics, for the first time, formulated by the present authors. Further, we discuss the origin of the fast response and the value of electrical conductivity of metal nanoparticles.

  7. Formulation of diclofenac for dermal delivery.

    Science.gov (United States)

    Goh, Choon Fu; Lane, Majella E

    2014-10-01

    Diclofenac (DF) was first synthesized in the 1960's and is currently available as ophthalmic, oral, parenteral, rectal and skin preparations. This review focuses on the administration of DF to the skin. As a member of the non-steroidal anti-inflammatory (NSAID) group of drugs the primary indications of DF are for the management of inflammation and pain but it is also used to treat actinic keratosis. The specific aims of this paper are to: (i) provide an overview of the pharmacokinetics and metabolism of DF following oral and topical administration; (ii) examine critically the various formulation approaches which have been investigated to enhance dermal delivery of DF; and (iii) identify new formulation</