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Sample records for release solid lipid

  1. Development and characterization of controlled release polar lipid microparticles of candesartan cilexetil by solid dispersion

    Science.gov (United States)

    Kamalakkannan, V; Puratchikody, A; Ramanathan, L

    2013-01-01

    Candesartan cilexetil (CC) is a newer class of angiotensin II receptor antagonist used for the treatment of hypertension. The solubility of the CC is very poor and its oral bioavailability is only 15%. The controlledrelease polar lipid microparticles of CC (formulations F1, F2, F3 and F4) were prepared using variable erodible lipophilic excipients like hydrogenated castor oil, stearic acid, cetostearyl alcohol and carnauba wax by fusion method. The particle sizes of polar lipid microparticles were less than 50 microns and they were irregular in shape. Drug content ranged between 98.96 ± 2.1 and 101.9 ± 1.6% were present in all the formulations. The formulation F3 showed better drug release throughout the study period in a controlled release manner. Moreover, the in vitro release showed that all the formulations were best fitted to Higuchi model. Accelerated stability studies indicated that there was no significant changes in the chemical and physical characteristics of the formulated drug product during initial and at the end of the study period. The FTIR and DSC studies showed that there was no interaction between the drug and lipophilic excipients and no polymorphic transitions in all formulations. The X-ray diffraction peak of solid dispersion indicated that the crystalline nature of CC disappeared and no new peaks could be observed, suggesting the absence of interaction between drug and excipients. PMID:24019822

  2. Polymeric and Solid Lipid Nanoparticles for Sustained Release of Carbendazim and Tebuconazole in Agricultural Applications

    Science.gov (United States)

    Campos, Estefânia Vangelie Ramos; Oliveira, Jhones Luiz De; da Silva, Camila Morais Gonçalves; Pascoli, Mônica; Pasquoto, Tatiane; Lima, Renata; Abhilash, P. C.; Fernandes Fraceto, Leonardo

    2015-09-01

    Carbendazim (MBC) (methyl-2-benzimidazole carbamate) and tebuconazole (TBZ) ((RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol) are widely used in agriculture for the prevention and control of fungal diseases. Solid lipid nanoparticles and polymeric nanocapsules are carrier systems that offer advantages including changes in the release profiles of bioactive compounds and their transfer to the site of action, reduced losses due to leaching or degradation, and decreased toxicity in the environment and humans. The objective of this study was to prepare these two types of nanoparticle as carrier systems for a combination of TBZ and MBC, and then investigate the release profiles of the fungicides as well as the stabilities and cytotoxicities of the formulations. Both nanoparticle systems presented high association efficiency (>99%), indicating good interaction between the fungicides and the nanoparticles. The release profiles of MBC and TBZ were modified when the compounds were loaded in the nanoparticles, and cytotoxicity assays showed that encapsulation of the fungicides decreased their toxicity. These fungicide systems offer new options for the treatment and prevention of fungal diseases in plants.

  3. Comparative study of sustained-release lipid microparticles and solid dispersions containing ibuprofen

    Directory of Open Access Journals (Sweden)

    Hugo Almeida

    2012-09-01

    Full Text Available Ibuprofen is one of the most important non-steroidal anti-inflammatory drugs used in the treatment of inflammatory diseases. In its pure state, ibuprofen presents poor physical and mechanical characteristics and its use in solid dosage forms needs the addition of excipients that improve these properties. The selection of the best excipients and the most suitable pharmaceutical dosage form to carry ibuprofen is very important for the industrial success of this drug. Given these factors, lipid microparticles and solid dispersions of ibuprofen with cetyl alcohol, stearic acid, and hydrogenated castor oil were prepared. These formulations were intended to improve the physical and mechanical characteristics and to sustain the release of this drug. Physical mixtures were also prepared with the same ingredients in similar proportions. The solid dispersions of ibuprofen/stearic acid and ibuprofen/hydrogenated castor oil showed the best flow characteristics compared with pure ibuprofen. Further, gelatin capsules filled with lipid microparticles and solid dispersions were submitted to dissolution tests in order to study the influence of the prepared systems in the release profiles of ibuprofen. Prolonged release of ibuprofen was achieved with the lipid microparticles and solid dispersions prepared with the different types of excipients.O ibuprofeno é um dos antiinflamatórios não esteróides mais utilizados no tratamento de patologias associadas a processos inflamatórios. Este fármaco, quando no seu estado puro, apresenta características físicas e mecânicas pouco satisfatórias e a sua utilização em formas sólidas só é possível se forem adicionados excipientes que permitam melhorar estas propriedades. A seleção dos excipientes ideais e da forma farmacêutica mais adequada para veicular o ibuprofeno é fundamental para o sucesso industrial deste fármaco. Tendo em conta estes fatores, prepararam-se micropartículas lipídicas e dispersões s

  4. Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology

    Directory of Open Access Journals (Sweden)

    Hanif Muhammad

    2017-12-01

    Full Text Available For preparing nebivolol loaded solid lipid microparticles (SLMs by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y1, entrapment efficiency (Y2 and drug release (Y3. SLMs having a 10-40 μm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to -40 mV. The obtained outcomes for Y1 (29-86 %, Y2 (45-83 % and Y3 (49-86 % were analyzed by polynomial equations and the suggested quadratic model were validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p 0.85 value (Korsmeyer- Peppas suggested slow erosion along with diffusion. The optimized SLMs have the potential to improve nebivolol oral bioavailability.

  5. Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology.

    Science.gov (United States)

    Hanif, Muhammad; Khan, Hafeez Ullah; Afzal, Samina; Mahmood, Asif; Maheen, Safirah; Afzal, Khurram; Iqbal, Nabila; Andleeb, Mehwish; Abbas, Nazar

    2017-12-20

    For preparing nebivolol loaded solid lipid microparticles (SLMs) by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y1), entrapment efficiency (Y2) and drug release (Y3). SLMs having a 10-40 μm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to -40 mV). The obtained outcomes for Y1 (29-86 %), Y2 (45-83 %) and Y3 (49-86 %) were analyzed by polynomial equations and the suggested quadratic model were validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p 0.85 value (Korsmeyer- Peppas) suggested slow erosion along with diffusion. The optimized SLMs have the potential to improve nebivolol oral bioavailability.

  6. Technology of stable, prolonged-release eye-drops containing Cyclosporine A, distributed between lipid matrix and surface of the solid lipid microspheres (SLM).

    Science.gov (United States)

    Wolska, Eliza; Sznitowska, Małgorzata

    2013-01-30

    The aim of this study was to prepare solid lipid microspheres (SLM) with incorporated Cyclosporine A (Cs), suitable for ocular application. For this purpose, SLM were formulated by using different lipids and three different nonionic surfactants. The SLM were produced using a hot emulsification method. The SLM dispersions contained 10, 20 or 30% of lipid (w/w) and up to 2% (w/w) of Cs. The size of the microspheres with Cs ranged from 1 to 15 μm. Physically stable SLM with Cs were prepared using Compritol, as a lipid matrix, and Tween 80, as a surfactant. In contrast, dispersion with Precirol alone, formed semi-solid gels during storage, while in formulations with Precirol and Miglyol, crystals of Cs were observed. In vitro release profile of Compritol formulations showed that 40% of Cs is released within 1h, while the release of the following 40% takes more time, depending on lipid content in the formulations. The large part of Cs, added to SLM formulations (from 45 to 80%), was found on the surface of microparticles, but no drug crystallization occurred during a long-term storage. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Investigation of protein distribution in solid lipid particles and its impact on protein release using coherent anti-Stokes Raman scattering microscopy

    DEFF Research Database (Denmark)

    Christophersen, Philip C.; Birch, Ditlev; Saarinen, Jukka

    2015-01-01

    The aim of this study was to gain new insights into protein distribution in solid lipid microparticles (SLMs) and subsequent release mechanisms using a novel label-free chemical imaging method, coherent anti-Stokes Raman scattering (CARS) microscopy. Lysozyme-loaded SLMs were prepared using...... in the solid lipid matrix, which required full lipolysis of the entire matrix to release lysozyme completely. Therefore, SLMs with lysozyme incorporated in an aqueous solution released lysozyme much faster than with lysozyme incorporated as a solid. In conclusion, CARS microscopy was an efficient and non......-destructive method for elucidating the distribution of lysozyme in SLMs. The interpretation of protein distribution and release during lipolysis enabled elucidation of protein release mechanisms. In future, CARS microscopy analysis could facilitate development of a wide range of protein-lipid matrices with tailor...

  8. Sustained release of piroxicam from solid lipid nanoparticle as an effective anti-inflammatory therapeutics in vivo.

    Science.gov (United States)

    Peng, Li-Hua; Wei, Wei; Shan, Ying-Hui; Chong, Yee-Song; Yu, Lian; Gao, Jian-Qing

    2017-01-01

    This study aims to investigate the solid lipid nanoparticle (SLN) as a novel vehicle for the sustained release and transdermal delivery of piroxicam, as well as to determine the anti-inflammation effect of piroxicam-loaded SLN. SLN formulation was optimized and the particle size, polydispersity index, zeta potential (ZP), encapsulation efficiency, drug release, and morphological properties were characterized. The transdermal efficiency and mechanism of the piroxicam-loaded SLNs were investigated in vitro. With the inflammation induced edema model in rat, the anti-inflammatory efficiency of piroxicam-enriched SLNs (Pir-SLNs) was evaluated. The SLN formulation was optimized as: lecithin 100 mg, glycerin monostearate 200 mg, and Tween (1%, w/w). The particle size is around 102 ± 5.2 nm with a PDI of 0.262. The ZP is 30.21 ± 2.05 mV. The prepared SLNs showed high entrapment efficiency of 87.5% for piroxicam. There is no interaction between piroxicam and the vehicle components. The presence of polymorphic form of lipid with higher drug content in the optimized Pir-SLNs enables the Pir-SLNs to release the drug with a sustained manner. Pir-SLNs with oleic acid as enhancer can radically diffuse into both the stratum corneum and dermal layer, as well as penetrate through the hair follicles and sebaceous glands with significantly higher density than the other control groups. Pir-SLNs promptly inhibited the inflammation since the 3rd hour after the treatment by decreasing the PGE 2 level. SLN was demonstrated to be a promising carrier for encapsulation and sustained release of piroxicam. Pir-SLN is a novel topical preparation with great potential for anti-inflammation application.

  9. Solid lipid particles for oral delivery of peptide and protein drugs III - the effect of fed state conditions on the in vitro release and degradation of desmopressin

    DEFF Research Database (Denmark)

    Christophersen, Philip C; Vaghela, Dimple; Müllertz, Anette

    2014-01-01

    The effect of food intake on the release and degradation of peptide drugs from solid lipid particles is unknown and was therefore investigated in vitro using different fed state media in a lipolysis model. Desmopressin was used as a model peptide and incorporated into solid lipid particles...... and the protease or desmopressin. Addition of a medium chain triglyceride, trilaurin, in combination with drug-loaded lipid particles diminished the food effect on the TG18 particles, and trilaurin is therefore proposed to be a suitable excipient for reduction of the food effect. Overall, the present study shows...... that strategies to reduce food effect, such as adding trilaurin, for lipid particle formulations should be considered as drug release from such formulations might be influenced by the presence of food in the gastrointestinal tract....

  10. Development of Houttuynia cordata Extract-Loaded Solid Lipid Nanoparticles for Oral Delivery: High Drug Loading Efficiency and Controlled Release

    Directory of Open Access Journals (Sweden)

    Ju-Heon Kim

    2017-12-01

    Full Text Available Houttuynia cordata (H. cordata has been used for diuresis and detoxification in folk medicine as well as a herbal medicine with antiviral and antibacterial activities. H. cordata extract-loaded solid lipid nanoparticles (H-SLNs were prepared with various concentration of poloxamer 188 or poloxamer 407 by a hot homogenization and ultrasonication method. H-SLNs dispersion was freeze-dried with or without trehalose as a cryoprotectant. The physicochemical characteristics of H-SLNs were evaluated by dynamic laser scattering (DLS, differential scanning calorimetry (DSC, Fourier transform infrared spectroscopy (FT-IR, and scanning electron microscopy (SEM. Additionally, the in vitro release and in vitro cytotoxicity of H-SLNs were measured. Encapsulation efficiencies of H-SLNs (as quercitrin were 92.9–95.9%. The SEM images of H-SLNs showed that H-SLNs have a spherical morphology. DSC and FT-IR showed that there were no interactions between ingredients. The increased extent of particle size of freeze-dried H-SLNs with trehalose was significantly lower than that of H-SLNs without trehalose. H-SLNs provided sustained release of quercitrin from H. cordata extracts. Cell viability of Caco-2 cells was over 70% according to the concentration of various formulation. Therefore, it was suggested that SLNs could be good carrier for administering H. cordata extracts.

  11. Investigation on Secondary Structure Perturbations of Proteins Embedded in Solid Lipid Matrices as a Novel Indicator of their Biological Activity upon In Vitro Release

    DEFF Research Database (Denmark)

    Zeeshan, Farrukh; Tabbassum, Misbah; Jorgensen, Lene

    2018-01-01

    encased in solid lipid matrices as a novel indicator of their stability upon in vitro release. Model proteins namely catalase and lysozyme were incorporated into lipid namely Precirol® AT05 (glycerol palmitostearate, melting point 58°C) at 30% w/w loading using melting and mixing and wet granulation...... aggregation for catalase which was increased using wet granulation. The biological activity of catalase was statistically different from that of control and was affected by the incorporation method and was found to be in alignment with ATR spectral changes and extent of aggregation. In conclusion, ATR...

  12. Preparation and evaluation of carvedilol-loaded solid lipid ...

    African Journals Online (AJOL)

    Keywords: Carvedilol, Solid lipid nanoparticles, Antihypertensive, Sustained release. Tropical Journal of ... Lipid particles are of great importance to drug researchers and ... toxic for human use and officially recognized as a pharmaceutical ...

  13. Solid lipid nanoparticles for parenteral drug delivery

    NARCIS (Netherlands)

    Wissing, S.A.; Kayser, Oliver; Muller, R.H.

    2004-01-01

    This review describes the use of nanoparticles based on solid lipids for the parenteral application of drugs. Firstly, different types of nanoparticles based on solid lipids such as "solid lipid nanoparticles" (SLN), "nanostructured lipid carriers" (NLC) and "lipid drug conjugate" (LDC)

  14. Sustained-release diclofenac potassium-loaded solid lipid microparticle based on solidified reverse micellar solution: in vitro and in vivo evaluation.

    Science.gov (United States)

    Chime, Salome Amarachi; Attama, Anthony Amaechi; Builders, Philip F; Onunkwo, Godswill C

    2013-01-01

    To formulate sustained-release diclofenac potassium-loaded solid lipid microparticles (SLMs) based on solidified reverse micellar solution (SRMS) and to evaluate the in vitro and in vivo properties. SRMS consisting of mixtures of Phospholipon® 90H and Softisan® 154 were used to formulate diclofenac potassium-loaded SLMs. Characterization based on the particle size and morphology, stability and encapsulation efficiency (EE%) were carried out on the SLMs. In vitro release was carried out in simulated intestinal fluid (pH 7.5). Anti-inflammatory and ulcerogenic properties were studied using rats. Maximum EE% of 95%, 94% and 93% were obtained for SLMs formulated with SRMS 1:1, 2:1 and 1:2, respectively. In vitro release showed about 85-90% drug release at 13 h. Diclofenac potassium-loaded SLMs showed good anti-inflammatory and gastro-protective properties. Diclofenac potassium-loaded SLMs based on SRMS could be used orally or parenterally under controlled conditions, for once daily administration.

  15. Characterization of Carbamazepine-Loaded Solid Lipid ...

    African Journals Online (AJOL)

    loaded solid lipid nanoparticles by RESS as well as their characterization has been achieved in this study. Keywords: Rapid expansion of supercritical fluid, Stearic acid, Solid lipid nanoparticles, Carbamazepine, Co-precipitation ...

  16. Application of Box-Behnken design for preparation of levofloxacin-loaded stearic acid solid lipid nanoparticles for ocular delivery: Optimization, in vitro release, ocular tolerance, and antibacterial activity.

    Science.gov (United States)

    Baig, Mirza Salman; Ahad, Abdul; Aslam, Mohammed; Imam, Syed Sarim; Aqil, Mohd; Ali, Asgar

    2016-04-01

    The aim of the present study was to develop and optimize levofloxacin loaded solid lipid nanoparticles for the treatment of conjunctivitis. Box-Behnken experimental design was applied for optimization of solid lipid nanoparticles. The independent variables were stearic acid as lipid (X1), Tween 80 as surfactant (X2) and sodium deoxycholate as co-surfactant (X3) while particle size (Y1) and entrapment efficiency (Y2) were the dependent variables. Further in vitro release and antibacterial activity in vitro were also performed. The optimized formulation of levofloxacin provides particle size of 237.82 nm and showed 78.71% entrapment efficiency and achieved flux 0.2,493 μg/cm(2)/h across excised goat cornea. In vitro release study showed prolonged drug release from the optimized formulation following Korsmeyer-Peppas model. Antimicrobial study revealed that the developed formulation possesses antibacterial activity against Staphylococcus aureus, and Escherichia coli equivalent to marketed eye drops. HET-CAM test demonstrated that optimized formulation was found to be non-irritant and safe for topical ophthalmic use. Our results concluded that solid lipid nanoparticles are an efficient carrier for ocular delivery of levofloxacin and other drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Solid lipid nanoparticles: A drug carrier system

    Directory of Open Access Journals (Sweden)

    Rashmi R Kokardekar

    2011-01-01

    Full Text Available Solid lipid nanoparticles (SLN are a type of nanoparticles. They are submicron colloidal carriers which are composed of physiological lipids, dispersed in water or in aqueous surfactant solutions. SLN have wide range of advantages over other types of nanoparticles. These include availability of large-scale production methods and no signs of cytotoxicity, which are main hindrances in the application of other types of nanoparticles. Hot and cold homogenization techniques are mainly employed for its production. They are mainly evaluated on the basis of their drug release profile and particle internal structure. The products based on SLN are under development. They have a very wide range of applications in cosmetics and pharmaceuticals. They can be applied for any purpose, for which nanoparticles have a distinct advantage. Thus, SLN can be used extensively as an alternative to the existing drug carrier systems, providing more flexibility with respect to the area of applications and also aspects for commercialization.

  18. Diclofenac salts, part 6: release from lipid microspheres.

    Science.gov (United States)

    Fini, Adamo; Cavallari, Cristina; Rabasco Alvarez, Antonio M; Rodriguez, Marisa Gonzalez

    2011-08-01

    The release of diclofenac (20%, w/w) was studied from lipidic solid dispersions using three different chemical forms (acid, sodium salt, and pyrrolidine ethanol salt) and two different lipid carriers (Compritol 888 ATO or Carnauba wax) either free or together with varying amounts (10%-30%, w/w) of stearic acid. Microspheres were prepared by ultrasound-assisted atomization of the molten dispersions and analyzed by scanning electron microscopy, differential scanning calorimetry, and hot stage microscopy. The effects of different formulations on the resulting drug release profiles as a function of pH were studied and the results were discussed. The formulation of the 18 systems and the chemical form of the drug were found to strongly affect the mode of the drug release. The solubility of the chemical forms in the lipid mixture is in the following order: pyrrolidine ethanol salt ≫ acid > sodium salt (according to the solubility parameters), and the nature of the systems thus obtained ranges from a matrix, for mutually soluble drug/carrier pairs, to a microcapsule, for pairs wherein mutual solubility is poor. Drug release from microspheres prepared by pure lipids was primarily controlled by diffusion, whereas the release from microspheres containing stearic acid was diffusion/erosion controlled at pH 7.4. Copyright © 2011 Wiley-Liss, Inc.

  19. Applications of lipid nanocarriers for solid tumors therapy: literature review

    International Nuclear Information System (INIS)

    Oliveira, Lidiane Correia de; Souza, Leonardo Gomes; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephania Fleury; Taveira, Eliseu Jose Fleury

    2012-01-01

    Introduction: Lipid nanocarriers are systems used to target drugs to its site of action and have attracted attention of the scientific community because they are biocompatible and biodegradable. These systems can target drugs to solid tumors, providing sustained drug release in the site of action, thus increasing the utility of the antineoplastic chemotherapy. Objective: To review the available literature on in vivo experiments with lipid nanocarriers containing cytotoxic drugs for solid tumors treatment. Method: A search study was carried out in Pubmed R database from 2007 to 2011, with subject descriptors: liposomes, lipid nanoparticles, cancer and in vivo, with the boolean operator 'and' among them, in English. Results: 1,595 papers related to the use of liposomes and 77 related to lipid nanoparticles were found. Few studies reported in vivo experiments with lipid nanoparticles (28 papers) compared to liposomes (472 papers), since liposomes were developed two decades before lipid nanoparticles. Four liposomal medicines have already been approved and are used in the clinic while only one medicine containing lipid nanoparticles is in phase I of clinical studies. Conclusion: The number of papers related to the use of nanotechnology for cancer treatment is increasing rapidly, making important to know the different kinds of nanocarriers and, especially, those which are already used in the clinic. There are only few clinical studies on lipid nanocarriers; however, these systems present an enormous potential to improve the clinical practice in oncology. (author)

  20. Sustained Cytotoxicity of Wogonin on Breast Cancer Cells by Encapsulation in Solid Lipid Nanoparticles

    Directory of Open Access Journals (Sweden)

    Jong-Suep Baek

    2018-03-01

    Full Text Available While wogonin has been known to have cytotoxicity against various cancer cells, its bioavailability and cytotoxicity are low due to its low water solubility. Therefore, wogonin-loaded solid lipid nanoparticles were fabricated using a hot-melted evaporation technique. The highest solubility of wogonin was observed in stearic acid. Hence, wogonin-loaded solid lipid nanoparticles were composed of stearic acid as the lipid matrix. The physicochemical properties of the wogonin-loaded solid lipid nanoparticles were evaluated by dynamic laser scattering and scanning electron microscopy. The wogonin-loaded solid lipid nanoparticles exhibited sustained and controlled release up to 72 h. In addition, it was observed that the wogonin-loaded solid lipid nanoparticles exhibited enhanced cytotoxicity and inhibited poly (ADP-ribose polymerase in MCF-7 breast cancer cells. Overall, the results indicate that wogonin-loaded solid lipid nanoparticles could be an efficient delivery system for the treatment of breast cancer.

  1. Nanostructured lipid carriers (NLCs) versus solid lipid nanoparticles (SLNs) for topical delivery of meloxicam.

    Science.gov (United States)

    Khalil, Rawia M; Abd-Elbary, A; Kassem, Mahfoz A; Ghorab, Mamdouh M; Basha, Mona

    2014-05-01

    The aim of this study was to develop nanostructured lipid carriers (NLCs) as well as solid lipid nanoparticles (SLNs) and evaluate their potential in the topical delivery of meloxicam (MLX). The effect of various compositional variations on their physicochemical properties was investigated. Furthermore, MLX-loaded lipid nanoparticles-based hydrogels were formulated and the gels were evaluated as vehicles for topical application. The results showed that NLC and SLN dispersions had spherical shapes with an average size between 215 and 430 nm. High entrapment efficiency was obtained ranging from 61.94 to 90.38% with negatively charged zeta potential in the range of -19.1 to -25.7 mV. The release profiles of all formulations exhibited sustained release characteristics over 48 h and the release rates increased as the amount of liquid lipid in lipid core increased. Finally, Precirol NLC with 50% Miglyol® 812 and its corresponding SLN were incorporated in hydrogels. The gels showed adequate pH, non-Newtonian flow with shear-thinning behavior and controlled release profiles. The biological evaluation revealed that MLX-loaded NLC gel showed more pronounced effect compared to MLX-loaded SLN gel. It can be concluded that lipid nanoparticles represent promising particulate carriers for topical application.

  2. Solid Lipid Nanoparticles of Guggul Lipid as Drug Carrier for Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Gaur

    2013-01-01

    Full Text Available Diclofenac sodium loaded solid lipid nanoparticles (SLNs were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG and plain carbopol gel containing drug (CG for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1 and stearic acid nanoparticle 1 (SAN-1 gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3 showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher Cmax than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile.

  3. Diclofenac sodium sustained release hot melt extruded lipid matrices.

    Science.gov (United States)

    Vithani, K; Cuppok, Y; Mostafa, S; Slipper, I J; Snowden, M J; Douroumis, D

    2014-08-01

    Sustained release diclofenac sodium (Df-Na) solid lipid matrices with Compritol® 888 ATO were developed in this study. The drug/lipid powders were processed via cold and hot melt extrusion at various drug loadings. The influence of the processing temperatures, drug loading and the addition of excipients on the obtained dissolution rates was investigated. The physicochemical characterization of the extruded batches showed the existence of crystalline drug in the extrudates with a small amount being solubilized in the lipid matrix. The drug content and uniformity on the tablet surface were also investigated by using energy dispersive X-ray microanalysis. The dissolution rates were found to depend on the actual Df-Na loading and the nature of the added excipients, while the effect of the processing temperatures was negligible. The dissolution mechanism of all extruded formulations followed Peppas-Korsemeyer law, based on the estimated determination coefficients and the dissolution constant rates, indicating drug diffusion from the lipid matrices.

  4. Production and characterization of nanostructured lipid carriers and solid lipid nanoparticles containing lycopene for food fortification.

    Science.gov (United States)

    Akhoond Zardini, Ali; Mohebbi, Mohebbat; Farhoosh, Reza; Bolurian, Shadi

    2018-01-01

    In this study, lycopene, was loaded on nanostructured lipid carrier and solid lipid nanoparticles using combination of high shear homogenization and ultrasonication method. Effect of applied lipids types, nanocarrier's type and lycopene loading on physicochemical properties of developed nanocarriers were studied. Particle sizes of developed nanocarriers were between 74.93 and 183.40 nm. Encapsulation efficiency of nanostructured lipid carrier was significantly higher than solid lipid nanoparticles. Morphological study of developed nanocarriers using scanning electron microscopy showed spherical nanoparticles with smooth surface. Lycopene was entrapped in nanocarriers without any chemical interaction with coating material according to Fourier transform infrared spectroscopy spectrum and differential scanning calorimetry thermogram. Glycerol monostearate containing nanoparticles showed phase separation after 30 days in 6 and 25 °C, whereas this event was not observed in nanosuspensions that produced by glycerol distearate. Lycopene release in gastrointestinal condition was studied by the dialysis bag method. To evaluate nanocarrier's potential for food fortification, developed lycopene-loaded nanocarriers were added to orange drink. Results of sensory analysis indicated that nanoencapsulation could obviate the poor solubility and tomato after taste of lycopene. Fortified sample with lycopene nanocarriers didn't show significant difference with blank orange drink sample except in orange odor.

  5. Effect of ingested lipids on drug dissolution and release with concurrent digestion: a modeling approach

    Science.gov (United States)

    Buyukozturk, Fulden; Di Maio, Selena; Budil, David E.; Carrier, Rebecca L.

    2014-01-01

    Purpose To mechanistically study and model the effect of lipids, either from food or self-emulsifying drug delivery systems (SEDDS), on drug transport in the intestinal lumen. Methods Simultaneous lipid digestion, dissolution/release, and drug partitioning were experimentally studied and modeled for two dosing scenarios: solid drug with a food-associated lipid (soybean oil) and drug solubilized in a model SEDDS (soybean oil and Tween 80 at 1:1 ratio). Rate constants for digestion, permeability of emulsion droplets, and partition coefficients in micellar and oil phases were measured, and used to numerically solve the developed model. Results Strong influence of lipid digestion on drug release from SEDDS and solid drug dissolution into food-associated lipid emulsion were observed and predicted by the developed model. 90 minutes after introduction of SEDDS, there was 9% and 70% drug release in the absence and presence of digestion, respectively. However, overall drug dissolution in the presence of food-associated lipids occurred over a longer period than without digestion. Conclusion A systems-based mechanistic model incorporating simultaneous dynamic processes occurring upon dosing of drug with lipids enabled prediction of aqueous drug concentration profile. This model, once incorporated with a pharmacokinetic model considering processes of drug absorption and drug lymphatic transport in the presence of lipids, could be highly useful for quantitative prediction of impact of lipids on bioavailability of drugs. PMID:24234918

  6. Polymer Coated Echogenic Lipid Nanoparticles with Dual Release Triggers

    Science.gov (United States)

    Nahire, Rahul; Haldar, Manas K.; Paul, Shirshendu; Mergoum, Anaas; Ambre, Avinash H.; Katti, Kalpana S.; Gange, Kara N.; Srivastava, D. K.; Sarkar, Kausik; Mallik, Sanku

    2013-01-01

    Although lipid nanoparticles are promising drug delivery vehicles, passive release of encapsulated contents at the target site is often slow. Herein, we report contents release from targeted, polymer coated, echogenic lipid nanoparticles in the cell cytoplasm by redox trigger and simultaneously enhanced by diagnostic frequency ultrasound. The lipid nanoparticles were polymerized on the external leaflet using a disulfide cross-linker. In the presence of cytosolic concentrations of glutathione, the lipid nanoparticles released 76% of encapsulated contents. Plasma concentrations of glutathione failed to release the encapsulated contents. Application of 3 MHz ultrasound for 2 minutes simultaneously with the reducing agent enhanced the release to 96%. Folic acid conjugated, doxorubicin loaded nanoparticles showed enhanced uptake and higher cytotoxicity in cancer cells overexpressing the folate receptor (compared to the control). With further developments, these lipid nanoparticles have the potential to be used as multimodal nanocarriers for simultaneous targeted drug delivery and ultrasound imaging. PMID:23394107

  7. 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.

  8. 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

  9. Impact of change of matrix crystallinity and polymorphism on ovalbumin release from lipid-based implants.

    Science.gov (United States)

    Duque, Luisa; Körber, Martin; Bodmeier, Roland

    2018-05-30

    The objectives of this study were to prepare lipid-based implants by hot melt extrusion (HME) for the prolonged release of ovalbumin (OVA), and to relate protein release to crystallinity and polymorphic changes of the lipid matrix. Two lipids, glycerol tristearate and hydrogenated palm oil, with different composition and degree of crystallinity were studied. Solid OVA was dispersed within the lipid matrixes, which preserved its stability during extrusion. This was partially attributed to a protective effect of the lipidic matrix. The incorporation of OVA decreased the mechanical strength of the implants prepared with the more crystalline matrix, glycerol tristearate, whereas it remained comparable for the hydrogenated palm oil because of stronger physical and non-covalent interactions between the protein and this lipid. This was also the reason for the faster release of OVA from the glycerol tristearate matrix when compared to the hydrogenated palm oil (8 vs. 28 weeks). Curing induced and increased crystallinity, and changes in the release rate, especially for the more crystalline matrix. In this case, both an increase and a decrease in release, were observed depending on the tempering condition. Curing at higher temperatures induced a melt-mediated crystallization and solid state transformation of the glycerol tristearate matrix and led to rearrangements of the inner structure with the formation of larger pores, which accelerated the release. In contrast, changes in the hydrogenated palm oil under the same curing conditions were less noticeable leading to a more robust formulation, because of less polymorphic changes over time. This study helps to understand the effect of lipid matrix composition and crystallinity degree on the performance of protein-loaded implants, and to establish criteria for the selection of a lipid carrier depending on the release profile desired. Copyright © 2018. Published by Elsevier B.V.

  10. DNA release from lipoplexes by anionic lipids: correlation with lipid mesomorphism, interfacial curvature, and membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Tarahovsky, Yury S.; Koynova, Rumiana; MacDonald, Robert C. (Northwestern)

    2010-01-18

    DNA release from lipoplexes is an essential step during lipofection and is probably a result of charge neutralization by cellular anionic lipids. As a model system to test this possibility, fluorescence resonance energy transfer between DNA and lipid covalently labeled with Cy3 and BODIPY, respectively, was used to monitor the release of DNA from lipid surfaces induced by anionic liposomes. The separation of DNA from lipid measured this way was considerably slower and less complete than that estimated with noncovalently labeled DNA, and depends on the lipid composition of both lipoplexes and anionic liposomes. This result was confirmed by centrifugal separation of released DNA and lipid. X-ray diffraction revealed a clear correlation of the DNA release capacity of the anionic lipids with the interfacial curvature of the mesomorphic structures developed when the anionic and cationic liposomes were mixed. DNA release also correlated with the rate of fusion of anionic liposomes with lipoplexes. It is concluded that the tendency to fuse and the phase preference of the mixed lipid membranes are key factors for the rate and extent of DNA release. The approach presented emphasizes the importance of the lipid composition of both lipoplexes and target membranes and suggests optimal transfection may be obtained by tailoring lipoplex composition to the lipid composition of target cells.

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

    Science.gov (United States)

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

    2016-01-01

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

  12. Brain-targeted solid lipid nanoparticles containing riluzole: preparation, characterization and biodistribution.

    Science.gov (United States)

    Bondì, Maria Luisa; Craparo, Emanuela Fabiola; Giammona, Gaetano; Drago, Filippo

    2010-01-01

    Developments within nanomedicine have revealed a great potential for drug delivery to the brain. In this study nanoparticulate systems as drug carriers for riluzole, with sufficiently high loading capacity and small particle size, were prepared to a reach therapeutic drug level in the brain. Solid lipid nanoparticles containing riluzole have great potential as drug-delivery systems for amyotrophic lateral sclerosis and were produced by using the warm oil-in-water microemulsion technique. The resulting systems obtained were approximately 88 nm in size and negatively charged. Drug-release profiles demonstrated that a drug release was dependent on medium pH. Biodistribution of riluzole blended into solid lipid nanoparticles was carried out after administration to rats and the results were compared with those obtained by riluzole aqueous dispersion administration. Rats were sacrificed at time intervals of 8, 16 and 30 h, and the riluzole concentration in the blood and organs such as the brain, liver, spleen, heart and kidney was determined. It was demonstrated that these solid lipid nanoparticles were able to successfully carry riluzole into the CNS. Moreover, a low drug biodistribution in organs such as the liver, spleen, heart, kidneys and lung was found when riluzole was administered as drug-loaded solid lipid nanoparticles. Riluzole-loaded solid lipid nanoparticles showed colloidal size and high drug loading, a greater efficacy than free riluzole in rats, a higher capability to carry the drug into the brain and a lower indiscriminate biodistribution.

  13. Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) for pulmonary application: a review of the state of the art.

    Science.gov (United States)

    Weber, S; Zimmer, A; Pardeike, J

    2014-01-01

    Drug delivery by inhalation is a noninvasive means of administration that has following advantages for local treatment for airway diseases: reaching the epithelium directly, circumventing first pass metabolism and avoiding systemic toxicity. Moreover, from the physiological point of view, the lung provides advantages for systemic delivery of drugs including its large surface area, a thin alveolar epithelium and extensive vasculature which allow rapid and effective drug absorption. Therefore, pulmonary application is considered frequently for both, the local and the systemic delivery of drugs. Lipid nanoparticles - Solid Lipid Nanoparticles and Nanostructured Lipid Carriers - are nanosized carrier systems in which solid particles consisting of a lipid matrix are stabilized by surfactants in an aqueous phase. Advantages of lipid nanoparticles for the pulmonary application are the possibility of a deep lung deposition as they can be incorporated into respirables carriers due to their small size, prolonged release and low toxicity. This paper will give an overview of the existing literature about lipid nanoparticles for pulmonary application. Moreover, it will provide the reader with some background information for pulmonary drug delivery, i.e., anatomy and physiology of the respiratory system, formulation requirements, application forms, clearance from the lung, pharmacological benefits and nanotoxicity. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting

    Energy Technology Data Exchange (ETDEWEB)

    Kharya, Parul; Jain, Ashish; Gulbake, Arvind; Shilpi, Satish; Jain, Ankit; Hurkat, Pooja [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India); Majumdar, Subrata [Bose Institute, Division of Molecular Medicine (India); Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2013-11-15

    The purpose of this study is to investigate the targeting potential of amino acid (phenylalanine)-coupled solid lipid nanoparticles (SLN) loaded with ionically complexed doxorubicin HCl (Dox). Ionic complexation was used to enhance the loading efficiency and release characteristics of water soluble form of Dox. l-Type amino acid transporters (LAT1) are highly expressed on blood brain barrier as well as on many brain cancer cells, thus targeting LAT1 using phenylalanine improved anticancer activity of prepared nanocarrier. The phenylalanine-coupled SLN were characterized by fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy, particle size, zeta potential, entrapment efficiency and in vitro release. The particle size of the resulting SLN was found to be in the range of 163.3 ± 5.2 to 113.0 ± 2.6 nm, with a slightly negative surface charge. In ex vivo study on C6 glioma cell lines, the cellular cytotoxicity of the SLN was highly increased when coupled with phenylalanine. In addition, stealthing sheath of PEG present on the surface of the SLN enhanced the cellular uptake of the SLN on C6 glioma cell line. Results of biodistribution and fluorescence studies clearly revealed that phenylalanine-coupled SLN could deliver high amount of drug into the brain tumor cells and showed the brain-targeting potential.

  15. Release and diffusional modeling of metronidazole lipid matrices.

    Science.gov (United States)

    Ozyazici, Mine; Gökçe, Evren H; Ertan, Gökhan

    2006-07-01

    In this study, the first aim was to investigate the swelling and relaxation properties of lipid matrix on diffusional exponent (n). The second aim was to determine the desired release profile of metronidazole lipid matrix tablets. We prepared metronidazole lipid matrix granules using Carnauba wax, Beeswax, Stearic acid, Cutina HR, Precirol ATO 5, and Compritol ATO 888 by hot fusion method and pressed the tablets of these granules. In vitro release test was performed using a standard USP dissolution apparatus I (basket method) with a stirring rate of 100 rpm at 37 degrees C in 900 ml of 0.1 N hydrochloric acid, adjusted to pH 1.2, as medium for the formulations' screening. Hardness, diameter-height ratio, friability, and swelling ratio were determined. Target release profile of metronidazole was also drawn. Stearic acid showed the highest and Carnauba wax showed the lowest release rates in all formulations used. Swelling ratios were calculated after the dissolution of tablets as 9.24%, 6.03%, 1.74%, and 1.07% for Cutina HR, Beeswax, Precirol ATO 5, and Compritol ATO 888, respectively. There was erosion in Stearic acid, but neither erosion nor swelling in Carnauba wax, was detected. According to the power law analysis, the diffusion mechanism was expressed as pure Fickian for Stearic acid and Carnauba wax and the coupling of Fickian and relaxation contributions for other Cutina HR, Beeswax, Compritol ATO 888, and Precirol ATO 5 tablets. It was found that Beeswax (kd=2.13) has a very close drug release rate with the target profile (kt=1.95). Our results suggested that swelling and relaxation properties of lipid matrices should be examined together for a correct evaluation on drug diffusion mechanism of insoluble matrices.

  16. Fabrication, appraisal, and transdermal permeation of sildenafil citrate-loaded nanostructured lipid carriers versus solid lipid nanoparticles

    Science.gov (United States)

    Elnaggar, Yosra SR; El-Massik, Magda A; Abdallah, Ossama Y

    2011-01-01

    Although sildenafil citrate (SC) is used extensively for erectile dysfunction, oral delivery of SC encounters many obstacles. Furthermore, the physicochemical characteristics of this amphoteric drug are challenging for delivery system formulation and transdermal permeation. This article concerns the assessment of the potential of nanomedicine for improving SC delivery and transdermal permeation. SC-loaded nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) were fabricated using a modified high-shear homogenization technique. Nanoparticle optimization steps included particle size analysis, entrapment efficiency (EE) determination, freeze-drying and reconstitution, differential scanning calorimetry, in vitro release, stability study and high-performance liquid chromatography analysis. Transdermal permeation of the nanocarriers compared with SC suspension across human skin was assessed using a modified Franz diffusion cell assembly. Results revealed that SLNs and NLCs could be optimized in the nanometric range (180 and 100 nm, respectively) with excellent EE (96.7% and 97.5%, respectively). Nanoparticles have significantly enhanced in vitro release and transdermal permeation of SC compared with its suspensions. Furthermore, transdermal permeation of SC exhibited higher initial release from both SLN and NLC formulations followed by controlled release, with promising implications for faster onset and longer drug duration. Nanomedicines prepared exhibited excellent physical stability for the study period. Solid nanoparticles optimized in this study successfully improved SC characteristics, paving the way for an efficient topical Viagra® product. PMID:22238508

  17. Drug Release and Skin Permeation from Lipid Liquid Crystalline Phases

    Science.gov (United States)

    Costa-Balogh, F. O.; Sparr, E.; Sousa, J. J. S.; Pais, A. A. C. C.

    We have studied drug release and skin permeation from several different liquid crystalline lipid formulations that may be used to control the respective release rates. We have studied the release and permeation through human skin of a water-soluble and amphiphilic drug, propranolol hydrochloride, from several formulations prepared with monoolein and phytantriol as permeation enhancers and controlled release excipients. Diolein and cineol were added to selected formulations. We observed that viscosity decreases with drug load, wich is compatible with the occurrence of phase changes. Diolein stabilizes the bicontinuous cubic phases leading to an increase in viscosity and sustained release of the drug. The slowest release was found for the cubic phases with higher viscosity. Studies on skin permeation showed that these latter formulations also presented lower permeability than the less viscous monoolein lamellar phases. Formulations containing cineol originated higher permeability with higher enhancement ratios. Thus, the various formulations are adapted to different circumstances and delivery routes. While a slow release is usually desired for drug sustained delivery, the transdermal route may require a faster release. Lamellar phases, which are less viscous, are more adapted to transdermal applications. Thus, systems involving lamellar phases of monoolein and cineol are good candidates to be used as skin permeation enhancers for propranolol hydrochloride.

  18. Layered lipid microcapsules for mesalazine delayed-release in children.

    Science.gov (United States)

    Balducci, Anna Giulia; Colombo, Gaia; Corace, Giuseppe; Cavallari, Cristina; Rodriguez, Lorenzo; Buttini, Francesca; Colombo, Paolo; Rossi, Alessandra

    2011-12-15

    The goal was to make available a delayed-release dosage form of mesalazine to be dispersed in water to facilitate swallowing in adults and children. Mesalazine microparticles containing carnauba wax were prepared by spray-congealing technique. A second step of spray-congealing of carnauba microparticles dispersed in liquefied stearic acid gave rise to mesalazine lipid microcapsules in which several carnauba microparticles remained embedded as cores in a reservoir structure. In order to favor their water dispersion, the lipid microcapsules were dry coated by tumbling them with different ratios of mannitol/lecithin microparticles prepared by spray-drying. Release rate measurements showed a delayed-release behavior, in particular a pH-dependence with less than 10% of drug released in acidic medium and complete release in phosphate buffer pH 7.4 in 4-5h. The layering with hydrophilic excipient microparticles allowed manufacturing of a pH-dependent dosage form suitable for extemporaneous oral use in adults and children. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Photoresponsive lipid-polymer hybrid nanoparticles for controlled doxorubicin release

    Science.gov (United States)

    Yao, Cuiping; Wu, Ming; Zhang, Cecheng; Lin, Xinyi; Wei, Zuwu; Zheng, Youshi; Zhang, Da; Zhang, Zhenxi; Liu, Xiaolong

    2017-06-01

    Currently, photoresponsive nanomaterials are particularly attractive due to their spatial and temporal controlled drug release abilities. In this work, we report a photoresponsive lipid-polymer hybrid nanoparticle for remote controlled delivery of anticancer drugs. This hybrid nanoparticle comprises three distinct functional components: (i) a poly(D,L-lactide-co-glycolide) (PLGA) core to encapsulate doxorubicin; (ii) a soybean lecithin monolayer at the interface of the core and shell to act as a molecular fence to prevent drug leakage; (iii) a photoresponsive polymeric shell with anti-biofouling properties to enhance nanoparticle stability, which could be detached from the nanoparticle to trigger the drug release via a decrease in the nanoparticle’s stability under light irradiation. In vitro results revealed that this core-shell nanoparticle had excellent light-controlled drug release behavior (76% release with light irradiation versus 10% release without light irradiation). The confocal microscopy and flow cytometry results also further demonstrated the light-controlled drug release behavior inside the cancer cells. Furthermore, a CCK8 assay demonstrated that light irradiation could significantly improve the efficiency of killing cancer cells. Meanwhile, whole-animal fluorescence imaging of a tumor-bearing mouse also confirmed that light irradiation could trigger drug release in vivo. Taken together, our data suggested that a hybrid nanoparticle could be a novel light controlled drug delivery system for cancer therapy.

  20. Preparation and characterization of solid lipid nanoparticles-a review.

    Science.gov (United States)

    Parhi, Rabinarayan; Suresh, Padilama

    2012-03-01

    In the present scenario, most of the developed and new discovered drugs are posing real challenge to the formulation scientists due to their poor aqueous solubility which in turn is responsible for poor bioavailability. One of the approach to overcome above problem is the packaging of the drug in to particulate carrier system. Among various carriers, lipid emerged as very attractive candidate because of its unique property of enhancing the bioavailability of poorly water soluble drugs. Solid lipid, one of the physical forms of lipid, is used to formulate nanoparticles, popularly known as Solid lipid nanoparticles (SLNs), as an alternative carrier system to emulsions, liposomes and polymeric micro- and nano-particles. SLNs combine advantages of the traditional systems but avoid some of their major disadvantages. This paper reviews numerous production techniques for SLNs along with their advantages and disadvantages. Special attention is paid to the characterization of the SLNs by using various analytical tools. It also emphasizes on physical state of lipid (supercooled melts, different lipid modifications).

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

    African Journals Online (AJOL)

    system with several advantages, including enhanced physical stability, dual loading ability for lipophilic and .... where kp is the release rate constant at the elapsed time t, n is a constant, where the value of n ≤ 0.45 indicates .... CXB and the hydrocarbon chain of the esterified fatty acids in the lipids. Upon emulsification CXB.

  2. Transforming lipid-based oral drug delivery systems into solid dosage forms: an overview of solid carriers, physicochemical properties, and biopharmaceutical performance.

    Science.gov (United States)

    Tan, Angel; Rao, Shasha; Prestidge, Clive A

    2013-12-01

    The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.

  3. Polymer-Induced Swelling of Solid-Supported Lipid Membranes

    Directory of Open Access Journals (Sweden)

    Martin Kreuzer

    2015-12-01

    Full Text Available In this paper, we study the interaction of charged polymers with solid-supported 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC membranes by in-situ neutron reflectivity. We observe an enormous swelling of the oligolamellar lipid bilayer stacks after incubation in solutions of poly(allylamine hydrochloride (PAH in D2O. The positively charged polyelectrolyte molecules interact with the lipid bilayers and induce a drastic increase in their d-spacing by a factor of ~4. Temperature, time, and pH influence the swollen interfacial lipid linings. From our study, we conclude that electrostatic interactions introduced by the adsorbed PAH are the main cause for the drastic swelling of the lipid coatings. The DMPC membrane stacks do not detach from their solid support at T > Tm. Steric interactions, also introduced by the PAH molecules, are held responsible for the stabilizing effect. We believe that this novel system offers great potential for fundamental studies of biomembrane properties, keeping the membrane’s natural fluidity and freedom, decoupled from a solid support at physiological conditions.

  4. Single-component solid lipid nanocarriers prepared with ultra-long chain amphiphilic lipids

    DEFF Research Database (Denmark)

    Wei, Wei; Lu, Xiaonan; Wang, Zegao

    2017-01-01

    HYPOTHESIS: Synthetic sugar alcohol mono-behenates with high melting points, surface activity and resistance to enzymatic lipolysis, are expected to form stable single-component solid lipid nanocarriers (SC-SLNs). The preparation methods and the polar head group of the molecules should affect the......-probe sonication method had a micelle structure with fenofibrate incorporated into a lipid monolayer. This study provides an insight into the systematic development of novel amphiphilic lipids for solid lipid-based drug delivery system.......HYPOTHESIS: Synthetic sugar alcohol mono-behenates with high melting points, surface activity and resistance to enzymatic lipolysis, are expected to form stable single-component solid lipid nanocarriers (SC-SLNs). The preparation methods and the polar head group of the molecules should affect...... using the lipolysis model. The structure and drug distribution of the nanocarriers were studied using AFM and TEM. FINDINGS: Both the polar head group of the molecules and the preparation methods affect the particle size and size distribution. Nanocarriers prepared with sorbitol mono-behenates showed...

  5. Mathematical modeling of drug release from lipid dosage forms.

    Science.gov (United States)

    Siepmann, J; Siepmann, F

    2011-10-10

    Lipid dosage forms provide an interesting potential for controlled drug delivery. In contrast to frequently used poly(ester) based devices for parenteral administration, they do not lead to acidification upon degradation and potential drug inactivation, especially in the case of protein drugs and other acid-labile active agents. The aim of this article is to give an overview on the current state of the art of mathematical modeling of drug release from this type of advanced drug delivery systems. Empirical and semi-empirical models are described as well as mechanistic theories, considering diffusional mass transport, potentially limited drug solubility and the leaching of other, water-soluble excipients into the surrounding bulk fluid. Various practical examples are given, including lipid microparticles, beads and implants, which can successfully be used to control the release of an incorporated drug during periods ranging from a few hours up to several years. The great benefit of mechanistic mathematical theories is the possibility to quantitatively predict the effects of different formulation parameters and device dimensions on the resulting drug release kinetics. Thus, in silico simulations can significantly speed up product optimization. This is particularly useful if long release periods (e.g., several months) are targeted, since experimental trial-and-error studies are highly time-consuming in these cases. In the future it would be highly desirable to combine mechanistic theories with the quantitative description of the drug fate in vivo, ideally including the pharmacodynamic efficacy of the treatments. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. 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

  7. DEVELOPMENT OF SUSTAINED RELEASE TABLETS CONTAINING SOLID DISPERSIONS OF BACLOFEN

    Directory of Open Access Journals (Sweden)

    K. H. Janardhana

    2015-07-01

    Full Text Available Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier. Free flowing solid dispersion granules were prepared by adsorbing the melt of the drug and carriers onto the surface of an adsorbent, Carbopol 934P followed by direct compression with HPMC K4M and HPMC K100 to obtain an solid dispersion loaded sustained release tablets. FTIR studies confirmed that the compatibility of drug and carriers. Differential scanning calorimetry (DSC and X-ray diffraction (XRD revealed partially amorphous structures of the drug in solid dispersion granules. The solid dispersion granules dissolved completely within 30 min, which was much faster than that of pure drug baclofen. The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2 and for up to 10 h in intestinal fluid (pH 6.8. A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly water-soluble drugs.

  8. DEVELOPMENT OF SUSTAINED RELEASE TABLETS CONTAINING SOLID DISPERSIONS OF BACLOFEN

    Directory of Open Access Journals (Sweden)

    K. H. Janardhana

    2013-12-01

    Full Text Available Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier. Free flowing solid dispersion granules were prepared by adsorbing the melt of the drug and carriers onto the surface of an adsorbent, Carbopol 934P followed by direct compression with HPMC K4M and HPMC K100 to obtain an solid dispersion loaded sustained release tablets. FTIR studies confirmed that the compatibility of drug and carriers. Differential scanning calorimetry (DSC and X-ray diffraction (XRD revealed partially amorphous structures of the drug in solid dispersion granules. The solid dispersion granules dissolved completely within 30 min, which was much faster than that of pure drug baclofen. The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2 and for up to 10 h in intestinal fluid (pH 6.8. A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly water-soluble drugs.

  9. Sulfite induces release of lipid mediators by alveolar macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Beck-Speier, I.; Dayal, N.; Maier, L. [GSF - National Research Center for Environment and Health, Neuherberg (Germany). Inst. for Inhalation Biology; Denzlinger, C. [Tuebingen Univ. (Germany). Dept. II, Medical Clinic; Haberl, C. [Tuebingen Univ. (Germany). Dept. III, Medical Clinic

    1998-03-01

    Air pollutants are supposed to modulate physiological responses of alveolar macrophages (AM). This study was addressed to the question whether at neutral pH sulfur(IV) species in comparison to sulfur(VI) species cause AM to release proinflammatory mediators and which pathways are involved in their generation. Supernatants obtained from canine AM treated with sulfite (0.1 mM to 2 mM) enhanced the respiratory burst of canine neutrophils, measured by lucigenin-dependent chemiluminescence, whereas supernatants derived from AM treated with sulfate (1 mM) did not. The neutrophil-stimulating activity released by sulfite-treated AM consisted of platelet-activating factor (PAF) and leukotriene B{sub 4} (LTB{sub 4}) as shown by desensitization of the platelet-activating factor (PAF) and leukotriene B{sub 4} (LTB{sub 4}) as shown by desensitization of the corresponding receptors. Inhibitors of phospholipase A{sub 2} substantially suppressed release of neutrophil-stimulating activity by sulfite-treated AM. Inhibition of 5-lipoxygenase in sulfite-treated AM also reduced neutrophil-stimulating activity, while inhibition of cyclooxygenase had no effect. In conclusion, sulfite induces AM to release lipid mediators via phospholipase A{sub 2}- and 5-lipoxygenase-dependent pathways. These mediators activate neutrophils via the receptors for PAF and LTB{sub 4}. (orig.)

  10. Encapsulation of solid dispersion in solid lipid particles for dissolution enhancement of poorly water-soluble drug.

    Science.gov (United States)

    Tran, Khanh Thi My; Vo, Toi Van; Tran, Phuong Ha-Lien; Lee, Beom-Jin; Duan, Wei; Tran, Thao Truong-Dinh

    2017-06-05

    The aim of this research was to engineer solid dispersion lipid particles (SD-SLs) in which a solid dispersion (SD) was encapsulated to form the core of solid lipid particles (SLs), thereby achieving an efficient enhancement in the dissolution of a poorly water-soluble drug. Ultrasonication was introduced into the process to obtain micro/nanoscale SLs. The mechanism of dissolution enhancement was investigated by analysing the crystalline structure, molecular interactions, and particle size of the formulations. The drug release from the SD-SLs was significantly greater than that from the SD or SLs alone. This enhancement in drug release was dependent on the preparation method and the drug-to-polymer ratio of the SD. With an appropriate amount of polymer in the SD, the solidification method had the potential to alter the drug crystallinity to an amorphous state, resulting in particle uniformity and molecular interactions in the SD-SLs. The proposed system provides a new strategy for enhancing the dissolution rate of poorly water-soluble drugs and further improving their bioavailability. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Preparation and evaluation of carvedilol-loaded solid lipid ...

    African Journals Online (AJOL)

    The SLNs were characterized in terms of entrapment efficiency, particle size, zeta potential, polydispersity index, cytotoxicity, solid state characterization and drug release. The stability of the formulations was investigated by monitoring their properties for a period of 3 months. Results: The mean size of the nanoparticles was ...

  12. Solid Lipid Particles for Oral Delivery of Peptide and Protein Drugs II - The Digestion of Trilaurin Protects Desmopressin from Proteolytic Degradation

    DEFF Research Database (Denmark)

    Christophersen, Philip Carsten; Zhang, Long; Müllertz, Anette

    2014-01-01

    , which is the same rank order as the lipid degradation rate. A reverse rank order was found for the protection of desmopressin from enzymatic degradation due to spatial separation of desmopressin from the protease. TG12 accelerated the release of desmopressin from all lipid particles when added as either...... and protease was determined. Trilaurin (TG12), trimyristin (TG14), tripalmitin (TG16), and tristearin (TG18) were used as lipid excipients to produce solid lipid microparticles. RESULTS: In the presence of lipase, the rate of drug release from different lipid particles was in the order of TG14 > TG16 > TG18...... drug-free microparticles to the lipolysis medium or incorporated in TG16 particles. Additionally, TG12 particles protected desmopressin from degradation when present in the lipolysis medium with the other lipid microparticles. CONCLUSIONS: TG12 is a very interesting lipid for oral lipid formulations...

  13. 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.

  14. Solid lipid dispersions: potential delivery system for functional ingredients in foods.

    Science.gov (United States)

    Asumadu-Mensah, Aboagyewa; Smith, Kevin W; Ribeiro, Henelyta S

    2013-07-01

    Structured solid lipid (SL) systems have the advantages of long-term physical stability, low surfactant concentrations, and may exhibit controlled release of active ingredients. In this research work, the potential use of high-melting SLs for the production of the above structured SL carrier systems was investigated. Dispersions containing either SL or blend of solid lipid and oil (SL+O) were produced by a hot melt high-pressure homogenization method. Experiments involved the use of 3 different SLs for the disperse phase: stearic acid, candelilla wax and carnauba wax. Sunflower oil was incorporated in the disperse phase for the production of the dispersions containing lipid and oil. In order to evaluate the practical aspects of structured particles, analytical techniques were used including: static light scattering to measure particle sizes, transmission electron microscopy (TEM) for investigating particle morphology and differential scanning calorimetry (DSC) to investigate the crystallization behavior of lipids in bulk and in dispersions. Results showed different mean particle sizes depending on the type of lipid used in the disperse phase. Particle sizes for the 3 lipids were: stearic acid (SL: 195 ± 2.5 nm; SL+O: 138 ± 6.0 nm); candelilla wax (SL: 178 ± 1.7 nm; SL+O: 144 ± 0.6 nm); carnauba wax (SL: 303 ± 1.5 nm; SL+O: 295 ± 5.0 nm). TEM results gave an insight into the practical morphology, showing plate-like and needle-like structures. DSC investigations also revealed that SL dispersions melted and crystallized at lower temperatures than the bulk. This decrease can be explained by the small particle sizes of the dispersion, the high-specific surface area, and the presence of a surfactant. © 2013 Institute of Food Technologists®

  15. Solid lipid nanoparticles loaded with iron to overcome barriers for treatment of iron deficiency anemia

    Directory of Open Access Journals (Sweden)

    Hosny KM

    2015-01-01

    Full Text Available Khaled Mohamed Hosny,1,2 Zainy Mohammed Banjar,3 Amani H Hariri,4 Ali Habiballah Hassan5 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; 3Department of Clinical Biochemistry, Faculty of medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Consultant Obstetrics and Gynecology, Hera Genaral Hospital, Makkah, Saudi Arabia; 5Department of Orthodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: According to the World Health Organization, 46% of the world’s children suffer from anemia, which is usually treated with iron supplements such as ferrous sulfate. The aim of this study was to prepare iron as solid lipid nanoparticles, in order to find an innovative way for alleviating the disadvantages associated with commercially available tablets. These limitations include adverse effects on the digestive system resulting in constipation and blood in the stool. The second drawback is the high variability in the absorption of iron and thus in its bioavailability. Iron solid lipid nanoparticles (Fe-SLNs were prepared by hot homogenization/ultrasonication. Solubility of ferrous sulfate in different solid lipids was measured, and effects of process variables such as the surfactant type and concentration, homogenization and ultrasonication times, and charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release and in vivo pharmacokinetics were studied in rabbits. Results indicated that Fe-SLNs consisted of 3% Compritol 888 ATO, 1% Lecithin, 3% Poloxamer 188, and 0.2% dicetylphosphate, with an average particle size of 25 nm with 92.3% entrapment efficiency. In vivo pharmacokinetic study revealed more than fourfold enhanced bioavailability. In

  16. Edible solid lipid nanoparticles (SLN as carrier system for antioxidants of different lipophilicity.

    Directory of Open Access Journals (Sweden)

    Kathleen Oehlke

    Full Text Available Ferulic acid (FA and tocopherol (Toc loaded solid lipid nanoparticles (SLN were prepared by a hot homogenisation method. The particle size distribution, zeta potential and melting behaviour of the SLN as well as the stability, encapsulation efficiency and radical scavenging activity of FA and Toc in the SLN were analysed. The different formulations containing up to 2.8 mg g-1 of FA or Toc were stable during at least 15 weeks of storage at room temperature. Despite partial degradation and / or release of FA and Toc during storage, significant radical scavenging activity was maintained. DSC measurements and radical scavenging tests after different time periods revealed that the re-structuring of the lipid matrix was connected to the enhanced antioxidant activity of Toc but did not affect the activity of FA.

  17. Enhanced rifampicin delivery to alveolar macrophages by solid lipid nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Chuan Junlan [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China); Li Yanzhen [Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery Technology and Pharmacokinetics (China); Yang Likai; Sun Xun [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China); Zhang Qiang [Peking University, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences (China); Gong Tao, E-mail: gongtaoy@126.com; Zhang Zhirong, E-mail: zrzzl@vip.sina.com [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China)

    2013-05-15

    The present study aimed at developing a drug delivery system targeting the densest site of tuberculosis infection, the alveolar macrophages (AMs). Rifampicin (RFP)-loaded solid lipid nanoparticles (RFP-SLNs) with an average size of 829.6 {+-} 16.1 nm were prepared by a modified lipid film hydration method. The cytotoxicity of RFP-SLNs to AMs and alveolar epithelial type II cells (AECs) was examined using MTT assays. The viability of AMs and AECs was above 80 % after treatment with RFP-SLNs, which showed low toxicity to both AMs and AECs. Confocal Laser Scanning Microscopy was employed to observe the interaction between RFP-SLNs and both AMs and AECs. After incubating the cells with RFP-SLNs for 2 h, the fluorescent intensity in AMs was more and remained longer (from 0.5 to 12 h) when compared with that in AECs (from 0.5 to 8 h). In vitro uptake characteristics of RFP-SLNs in AMs and AECs were also investigated by detection of intracellular RFP by High performance liquid chromatography. Results showed that RFP-SLNs delivered markedly higher RFP into AMs (691.7 ng/mg in cultured AMs, 662.6 ng/mg in primary AMs) than that into AECs (319.2 ng/mg in cultured AECs, 287.2 ng/mg in primary AECs). Subsequently, in vivo delivery efficiency and the selectivity of RFP-SLNs were further verified in Sprague-Dawley rats. Under pulmonary administration of RFP-SLNs, the amount of RFP in AMs was significantly higher than that in AECs at each time point. Our results demonstrated that solid lipid nanoparticles are a promising strategy for the delivery of rifampicin to alveolar macrophages selectively.

  18. Sulfur Release from Cement Raw Materials during Solid Fuel Combustion

    DEFF Research Database (Denmark)

    Nielsen, Anders Rooma; Larsen, Morten B.; Glarborg, Peter

    2011-01-01

    During combustion of solid fuels in the material inlet end of cement rotary kilns, local reducing conditions can occur and cause decomposition of sulfates from cement raw materials. Decomposition of sulfates is problematic because it increases the gas-phase SO2 concentration, which may cause...... deposit formation in the kiln system. SO2 release from cement raw materials during combustion of solid fuels has been studied experimentally in a high temperature rotary drum. The fuels were tire rubber, pine wood, petcoke, sewage sludge, and polypropylene. The SO2 release from the raw materials...

  19. Preparation and characterization of solid lipid nanoparticles loaded with frankincense and myrrh oil

    Directory of Open Access Journals (Sweden)

    Shi F

    2012-04-01

    Full Text Available Feng Shi, Ji-Hui Zhao, Ying Liu, Zhi Wang, Yong-Tai Zhang, Nian-Ping FengSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of ChinaAbstract: The aim of the present study was to prepare solid lipid nanoparticles (SLNs for the oral delivery of frankincense and myrrh essential oils (FMO. Aqueous dispersions of SLNs were successfully prepared by a high-pressure homogenization method using Compritol 888 ATO as the solid lipid and soybean lecithin and Tween 80 as the surfactants. The properties of the SLNs such as particle size, zeta potential (ZP, and drug encapsulation efficiency (EE were investigated. The morphology of SLNs was observed by transmission electron microscopy (TEM. The crystallinity of the formulation was analyzed by differential scanning calorimetry (DSC and X-ray diffraction (XRD. In addition, drug evaporation release and antitumor activity were also studied. Round SLNs with a mean size of 113.3 ± 3.6 nm, a ZP of -16.8 ± 0.4 mV, and an EE of 80.60% ± 1.11% were obtained. DSC and XRD measurements revealed that less ordered structures were formed in the inner cores of the SLN particles. Evaporation loss of the active components in FMO could be reduced in the SLNs. Furthermore, the SLN formulation increased the antitumor efficacy of FMO in H22-bearing Kunming mice. Hence, the presented SLNs can be used as drug carriers for hydrophobic oil drugs extracted from traditional Chinese medicines.Keywords: solid lipid nanoparticles, frankincense oil, myrrh oil, evaporation release, antitumor activity, traditional Chinese medicine

  20. Alcohol dose dumping: The influence of ethanol on hot-melt extruded pellets comprising solid lipids.

    Science.gov (United States)

    Jedinger, N; Schrank, S; Mohr, S; Feichtinger, A; Khinast, J; Roblegg, E

    2015-05-01

    The objective of the present study was to investigate interactions between alcohol and hot-melt extruded pellets and the resulting drug release behavior. The pellets were composed of vegetable calcium stearate as matrix carrier and paracetamol or codeine phosphate as model drugs. Two solid lipids (Compritol® and Precirol®) were incorporated into the matrix to form robust/compact pellets. The drug release characteristics were a strong function of the API solubility, the addition of solid lipids, the dissolution media composition (i.e., alcohol concentration) and correspondingly, the pellet wettability. Pellets comprising paracetamol, which is highly soluble in ethanol, showed alcohol dose dumping regardless of the matrix composition. The wettability increased with increasing ethanol concentrations due to higher paracetamol solubilities yielding increased dissolution rates. For pellets containing codeine phosphate, which has a lower solubility in ethanol than in acidic media, the wettability was a function of the matrix composition. Dose dumping occurred for formulations comprising solid lipids as they showed increased wettabilities with increasing ethanol concentrations. In contrast, pellets comprising calcium stearate as single matrix component showed robustness in alcoholic media due to wettabilities that were not affected by the addition of ethanol. The results clearly indicate that the physico-chemical properties of the drug and the matrix systems are crucial for the design of ethanol-resistant dosage forms. Moreover, hydrophobic calcium stearate can be considered a suitable matrix system that minimizes the risk of ethanol-induced dose dumping for certain API's. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Novel sulpiride-loaded solid lipid nanoparticles with enhanced intestinal permeability

    Directory of Open Access Journals (Sweden)

    Ibrahim WM

    2013-12-01

    Full Text Available Waheed M Ibrahim,1 Abdullah H AlOmrani,2 Alaa Eldeen B Yassin31Drug Sector, Saudi Food and Drug Authority, 2Department of Pharmaceutics, College of Pharmacy, King Saud University, 3Department of Pharmaceutical Sciences, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, National Guard Health Affairs, Riyadh, Saudi ArabiaBackground: Solid lipid nanoparticles (SLN, novel drug delivery carriers, can be utilized in enhancing both intestinal permeability and dissolution of poorly absorbed drugs. The aim of this work was to enhance the intestinal permeability of sulpiride by loading into SLN.Methods: A unique ultrasonic melt-emulsification method with minimum stress conditions was used for the preparation of SLN. The mixture of the drug and the melted lipids was simply dispersed in an aqueous solution of a surfactant at a temperature that was 10°C higher than the melting points of the lipids using probe sonication, and was then simultaneously dispersed in cold water. Several formulation parameters were optimized, including the drug-to-lipid ratio, and the types of lipids and surfactants used. The produced SLN were evaluated for their particle size and shape, surface charge, entrapment efficiency, crystallinity of the drug and lipids, and the drug release profile. The rat everted sac intestine model was utilized to evaluate the change in intestinal permeability of sulpiride by loading into SLN.Results: The method adopted allowed successful preparation of SLN with a monodispersed particle size of 147.8–298.8 nm. Both scanning electron microscopic and atomic force microscopic images showed uniform spherical particles and confirmed the sizes determined by the light scattering technique. Combination of triglycerides with stearic acid resulted in a marked increase in zeta potential, entrapment efficiency, and drug loading; however, the particle size was increased. The type of surfactant used was critical for particle size

  2. Biowaiver monographs for immediate release solid oral dosage forms: cimetidine.

    NARCIS (Netherlands)

    Jantratid, E; Prakongpan, S; Dressman, J B; Amidon, G L; Junginger, H E; Midha, K K; Barends, D M

    2006-01-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing cimetidine are reviewed. According to the current Biopharmaceutics Classification System (BCS), cimetidine would be assigned

  3. Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a potential Anticancer Drug Delivery System

    Science.gov (United States)

    Patel, Meghavi

    Solid lipid nanoparticles (SLNs) consist of spherical solid lipid particles in the nanometer size range, which are dispersed in water or in an aqueous surfactant solution. SLN technology represents a promising new approach to deliver hydrophilic as well as lipophilic drugs. The commercialization of SLN technology remains limited despite numerous efforts from researchers. The purpose of this research was to advance SLN preparation methodology by investigating the feasibility of preparing glyceryl monostearate (GMS) nanoparticles by using three preparation methods namely microemulsion technique, magnetic stirring technique and temperature modulated solidification technique of which the latter two were developed in our laboratory. An anticancer drug 5-fluorouracil was incorporated in the SLNs prepared via the temperature modulated solidification process. Optimization of the magnetic stirring process was performed to evaluate how the physicochemical properties of the SLN was influenced by systematically varying process parameters including concentration of the lipid, concentration of the surfactant, type of surfactant, time of stirring and temperature of storage. The results demonstrated 1:2 GMS to tween 80 ratio, 150 ml dispersion medium and 45 min stirring at 4000 RPM speed provided an optimum formulation via the temperature modulated solidification process. SLN dispersions were lyophilized to stabilize the solid lipid nanoparticles and the lyophilizates exhibited good redispersibility. The SLNs were characterized by particle size analysis via dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), drug encapsulation efficiency and in vitro drug release studies. Particle size of SLN dispersion prepared via the three preparation techniques was approximately 66 nm and that of redispersed lyophilizates was below 500 nm. TEM images showed spherical to oval particles that were less dense in the core

  4. Orodispersible tablets containing taste-masked solid lipid pellets with metformin hydrochloride: Influence of process parameters on tablet properties.

    Science.gov (United States)

    Petrovick, Gustavo Freire; Kleinebudde, Peter; Breitkreutz, Jörg

    2018-01-01

    Compaction of multiparticulates into tablets, particularly into orodispersible tablets (ODTs), is challenging. The compression of pellets, made by solid lipid extrusion/spheronization processes, presents peculiar difficulties since solid lipids usually soften or melt at relatively low temperature ranges and due to applied mechanical forces. Until now, there are no reports in literature about the development of ODTs based on solid lipid pellets. To investigate the feasibility of producing such tablets, a design of experiment (DoE) approach was performed to elucidate the influence of compression force and amount of two co-processed excipients (Ludiflash ® and Parteck ® ODT) on properties of the tablets (friability, tensile strength, and disintegration time). ODTs (15 mm, flat-faced) with solid lipid pellets (250-1000 µm in diameter) containing 500 mg of metformin HCl, presenting immediate drug release profile and taste-masked properties, were targeted. During compression, a strong lamination of the tablets containing Parteck ® ODT was observed. This phenomenon was prominently observed when high compression forces (≥5 kN) and high excipient amounts (≥40%; w/w) were used. On the other hand, the DoE focused on tablets with Ludiflash ® showed better results regarding the production of ODTs. A positive influence of the compression force on the tensile strength and disintegration time of the tablets, regarding specifications of the Ph. Eur., was observed. The increase in the amount of this excipient resulted in fast disintegrating tablets, however, a negative influence on the tensile strength was noticed. After optimization of the parameters and formulation, based on the DoE results and considering the Ph. Eur. specifications for tablets, ODTs based on lipid pellets containing metformin HCl presenting immediate release profile (85% drug release in less than 30 min) and taste-masked properties (determined by an electronic tongue) were successfully

  5. Chitosan-coupled solid lipid nanoparticles: Tuning nanostructure and mucoadhesion.

    Science.gov (United States)

    Sandri, Giuseppina; Motta, Simona; Bonferoni, Maria Cristina; Brocca, Paola; Rossi, Silvia; Ferrari, Franca; Rondelli, Valeria; Cantù, Laura; Caramella, Carla; Del Favero, Elena

    2017-01-01

    Solid Lipid Nanoparticles (SLNs) composed of biodegradable physiological lipids have been widely proposed as efficient drug delivery systems, also for ophthalmic administration. Recently, chitosan-associated-SLNs have been developed to further improve the residence time of these colloidal systems in the precorneal area by means of mucoadhesive interaction. In the present study, a one-step preparation protocol was used aiming both at scale-up ease and at stronger coupling between chitosan and SLNs. The resulting particles were chitosan associated-SLNs (CS-SLNs). These nanoparticles were characterized, as compared to both the chitosan-free and the usual chitosan-coated ones, by applying a multi-technique approach: light, neutron and X-ray scattering, Zeta-potential, AFM, calorimetry. It was assessed that, while keeping the features of nano-size and surface-charge required for an efficient vector, these new nanoparticles display a strong and intimate interaction between chitosan and SLNs, far more settled than the usual simple coverage. Moreover, this one-step preparation method allows to obtain a strong and intimate interaction between chitosan and SLNs, firmer than the usual simple coating. This confers to the CS-SLNs an improved mucoadhesion, opening the way for a high-performing ophthalmic formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Cholesterylbutyrate Solid Lipid Nanoparticles as a Butyric Acid Prodrug

    Directory of Open Access Journals (Sweden)

    Alessandro Mauro

    2008-02-01

    Full Text Available Cholesterylbutyrate (Chol-but was chosen as a prodrug of butyric acid.Butyrate is not often used in vivo because its half-life is very short and therefore too largeamounts of the drug would be necessary for its efficacy. In the last few years butyric acid'santi-inflammatory properties and its inhibitory activity towards histone deacetylases havebeen widely studied, mainly in vitro. Solid Lipid Nanoparticles (SLNs, whose lipid matrixis Chol-but, were prepared to evaluate the delivery system of Chol-but as a prodrug and totest its efficacy in vitro and in vivo. Chol-but SLNs were prepared using the microemulsionmethod; their average diameter is on the order of 100-150 nm and their shape is spherical.The antineoplastic effects of Chol-but SLNs were assessed in vitro on different cancer celllines and in vivo on a rat intracerebral glioma model. The anti-inflammatory activity wasevaluated on adhesion of polymorphonuclear cells to vascular endothelial cells. In thereview we will present data on Chol-but SLNs in vitro and in vivo experiments, discussingthe possible utilisation of nanoparticles for the delivery of prodrugs for neoplastic andchronic inflammatory diseases.

  7. Enhanced photocytotoxicity of curcumin delivered by solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Jiang S

    2016-12-01

    Full Text Available Shan Jiang,1 Rongrong Zhu,1 Xiaolie He,1 Jiao Wang,1 Mei Wang,1 Yechang Qian,2 Shilong Wang1 1Tenth People’s Hospital, School of Life Science and Technology, Tongji University, 2Department of Respiratory Disease, Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, People’s Republic of China Abstract: Curcumin (Cur is a promising photosensitizer that could be used in photodynamic therapy. However, its poor solubility and hydrolytic instability limit its clinical use. The aim of the present study was to encapsulate Cur into solid lipid nanoparticles (SLNs in order to improve its therapeutic activity. The Cur-loaded SLNs (Cur-SLNs were prepared using an emulsification and low-temperature solidification method. The functions of Cur and Cur-SLNs were studied on the non-small cell lung cancer A549 cells for photodynamic therapy. The results revealed that Cur-SLNs induced ~2.27-fold toxicity higher than free Cur at a low concentration of 15 µM under light excitation, stocking more cell cycle at G2/M phase. Cur-SLNs could act as an efficient drug delivery system to increase the intracellular concentration of Cur and its accumulation in mitochondria; meanwhile, the hydrolytic stability of free Cur could be improved. Furthermore, Cur-SLNs exposed to 430 nm light could produce more reactive oxygen species to induce the disruption of mitochondrial membrane potential. Western blot analysis revealed that Cur-SLNs increased the expression of caspase-3, caspase-9 proteins and promoted the ratio of Bax/Bcl-2. Overall, the results from these studies demonstrated that the SLNs could enhance the phototoxic effects of Cur. Keywords: photodynamic therapy, curcumin, solid lipid nanoparticles, drug delivery, reactive oxygen species

  8. 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

  9. Mydriatics release from solid and semi-solid ophthalmic formulations using different in vitro methods.

    Science.gov (United States)

    Pescina, Silvia; Macaluso, Claudio; Gioia, Gloria Antonia; Padula, Cristina; Santi, Patrizia; Nicoli, Sara

    2017-09-01

    The aim of the present paper was the development of semi-solid (hydrogels) and solid (film) ophthalmic formulations for the controlled release of two mydriatics: phenylephrine and tropicamide. The formulations - based on polyvinylalcohol and hyaluronic acid - were characterized, and release studies were performed with three different in vitro set-ups, i.e. Franz-type diffusion cell, vial method and inclined plane; for comparison, a solution and a commercial insert, both clinically used to induce mydriasis, were evaluated. Both gels and film allowed for a controlled release of drugs, appearing a useful alternative for mydriatics administration. However, the release kinetic was significantly influenced by the method used, highlighting the need for optimization and standardization of in vitro models for the evaluation of drug release from ophthalmic dosage forms.

  10. Development of solid lipid nanoparticles for enhanced solubility of poorly soluble drugs

    DEFF Research Database (Denmark)

    Potta, Sriharsha Gupta; Minemi, Sriharsha; Nukala, Ravi Kumar

    2010-01-01

    Cyclosporine (CyA) solid lipid nanoparticles were prepared by using a solvent free high pressure homogenization process. CyA was incorporated into SLNs that consisted of stearic acid, trilaurin or tripalmitin lipid solid cores in order to enhance drug solubility. The process was conducted...

  11. Preparation, characterization and pharmacokinetics of enrofloxacin-loaded solid lipid nanoparticles: influences of fatty acids.

    Science.gov (United States)

    Xie, Shuyu; Zhu, Luyan; Dong, Zhao; Wang, Xiaofang; Wang, Yan; Li, Xihe; Zhou, WenZhong

    2011-04-01

    Enrofloxacin-loaded solid lipid nanoparticles (SLN) were prepared using fatty acids (tetradecanoic acid, palmitic acid, stearic acid) as lipid matrix by hot homogenization and ultrasonication method. The effect of fatty acids on the characteristics and pharmacokinetics of the SLN were investigated. The results showed that the encapsulation efficiency and loading capacity of nanoparticles varied with fatty acids in the order of stearic acid>palmitic acid>tetradecanoic acid. Furthermore, stearic acid-SLN had larger particle size, bigger polydispersity index (PDI) and higher zeta potential compared with the other two fatty acid formulated SLN. The SLN showed sustained releases in vitro and the released enrofloxacin had the same antibacterial activity as that of the native enrofloxacin. Although in vitro release exhibited similar patterns, within 24 h the releasing rates of the three formulations were significantly different (tetradecanoic acid-SLN>palmitic acid-SLN>stearic acid-SLN). Pharmacokinetic study after a single dose of intramuscular administration to mice demonstrated that tetradecanoic acid-SLN, palmitic acid-SLN, and stearic acid-SLN increased the bioavailability by 6.79, 3.56 and 2.39 folds, and extended the mean residence time (MRT) of the drug from 10.60 h to 180.36, 46.26 and 19.09 h, respectively. These results suggest that the enrofloxacin-fatty acid SLN are promising formulations for sustained release while fatty acids had significant influences on the characteristics and performances of the SLN. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. IVABRADINE LOADED SOLID LIPID MICROPARTICLES: FORMULATION, CHARACTERIZATION AND OPTIMIZATION BY CENTRAL COMPOSITE ROTATABLE DESIGN.

    Science.gov (United States)

    Hanif, Muhammad; Khan, Hafeez Ullah; Afzal, Samina; Sher, Muhammad

    2017-01-01

    The current research focused on improvement of oral bioavailability and decrease in dosing frequency of ivabradine (Iva) in order to enhance patient compliance by formulating novel sustained release Iva loaded solid lipid microparticles (SLMs) with the help of melt emulsification technique. SLMs formulations were designed with the help of three level central composite rotatable design (CCRD) to study the impact of independent variables like lipid concentration, surfactant concentration and stirring speed on responses - percentage yield (Y,) and entrapment efficiency (Y2). Compatibility between the drug and bees wax (BW) was checked by conducting Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). SLMs were further evaluated for rheological behavior, zeta potential, particle size and for morphology by scanning'electron microscope (SEM). The release of drug from SLMs was conducted by USP type-Il apparatus at pH 1.2, pH 6.8 and data were analyzed by different kinetic models like zero order, first order, Higuchi model, Korsmeyer-Peppas and Hixon-Crowell models. The rheo- logical studies approved the good flow behavior of SLMs and spherical smooth surface of SLMs was observed from SEM. DSC, FTIR and XRD studies concluded the lack of any possible interaction between formulation components. The size-of SLMs ranged from 300 to 500 pm and zeta potential study showed the presence of higher negative charge (-30 to -52 mV). Response Y, varied from 53 to 90% and response Y2 ranged from 29 to 78% indicating the effect of formulation variables. The obtained outcomes were analyzed by second order polynomial equation and suggested quadratic model was also validated. SLMs released Iva from 54 to 90% at pH 6.8 and was significantly (p 0.05) affected by BW concentration. The release mechanism followed the zero order and Korsmeyer-Peppas (n 0.85) kinetic models suggesting slow erosion along with diffusion

  13. PEG-stearate coated solid lipid nanoparticles as levothyroxine carriers for oral administration

    Science.gov (United States)

    Kashanian, Soheila; Rostami, Elham

    2014-03-01

    In this study, poly ethylene glycol 100 stearate (PEG 100-S) was used to prepare coated solid lipid nanoparticles with loading levothyroxine sodium (levo-loaded PEG 100-S-coated SLNs) by microemulsification technique. Evaluation of the release kinetic of prepared colloidal carriers was conducted. The particle size and zeta potential of levo-loaded PEG 100-S-coated SLNs have been measured to be 187.5 nm and -23.0 mV, respectively, using photon correlation spectroscopy (PCS). Drug entrapment efficiency (EE) was calculated to be 99 %. Differential scanning calorimetry indicated that the majority of drug loaded in PEG 100-S-coated SLNs were in amorphous state which could be considered desirable for drug delivery. The purpose of this study was to develop a new nanoparticle system, consisting lipid nanoparticles coated with PEG 100-S. The modification procedure led to a reduction in the zeta potential values, varying from -40.0 to -23.0 mV for the uncoated and PEG-coated SLNs, respectively. Stability results of the nanoparticles in gastric and intestinal media show that the low pH of the gastric medium is responsible for the critical aggregation and degradation of the uncoated lipid nanoparticles. PEG 100-S-coated SLNs were more stable due to their polymer coating layer which prevented aggregation of SLNs. Consequently, it is possible that the PEG surrounds the particles reducing the attachment of enzymes and further degradation of the triglyceride cores. Shape and surface morphology of particles were determined by transition electron microscopy and scanning electron microscopy that revealed spherical shape of nanoparticles. In vitro drug release of PEG 100-S-coated SLNs was characterized using diffusion cell which showed a controlled release for drug.

  14. Stability and antimicrobial effect of amikacin-loaded solid lipid nanoparticles

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    Solmaz Ghaffari

    2010-12-01

    Full Text Available Solmaz Ghaffari1, Jaleh Varshosaz1, Afrooz Saadat2, Fatemeh Atyabi21Department of Pharmaceutics, Faculty of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; 2Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranAbstract: Solid lipid nanoparticles (SLNs of amikacin were designed in this study for pulmonary delivery to reduce the dose or its administration intervals leading to reduction of its toxicities especially in long term treatment. Nanoparticles of amikacin were prepared from cholesterol by solvent diffusion technique and homogenization. The size, zeta potential, loading efficiency, and release profile of the nanoparticles were studied. The conventional broth macrodilution tube method was used to determine the minimum inhibitory concentration (MIC and minimum bacteriostatic concentration (MBC of amikacin SLNs with respect to Pseudomonas aeruginosa in vitro. To guarantee the stability of desired SLNs, they were lyophilized using cryoprotectants. Results showed that considering the release profile of amikacin from the studied nanocarrier, MIC and MBC of amikacin could be about two times less in SLNs of amikacin compared to the free drug. Therefore, fewer doses of amikacin in SLNs can clear the infection with less adverse effects and more safety. Particle size enlargement after lyophilization of desired SLNs after two months storage was limited in comparison with non-lyophilized particles, 996 and 194 nm, respectively. Zeta potential of lyophilized particles was increased to +17 mV from +4 mV before lyophilization. Storage of particles in higher temperature caused accelerated drug release.Keywords: amikacin, antimicrobial effects, Pseudomonas aeruginosa, solid lipid nanoparticles, stability

  15. Preparation and characterization of solid lipid nanoparticles containing cyclosporine by the emulsification-diffusion method

    Directory of Open Access Journals (Sweden)

    Zaida Urbán-Morlán

    2010-08-01

    Full Text Available Zaida Urbán-Morlán1, Adriana Ganem-Rondero1, Luz María Melgoza-Contreras2, José Juan Escobar-Chávez1,2, María Guadalupe Nava-Arzaluz1, David Quintanar-Guerrero11División de Estudios de Posgrado (Tecnología Farmacéutica, Facultad de Estudios Superiores Cuautitlán-Universidad Nacional Autónoma de México, Estado de México, México; 2Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso, Colonia Villa Quietud, MéxicoAbstract: Solid lipid nanoparticles (SLNs have been used for carrying different therapeutic agents because they improve absorption and bioavailability. The aim of the study was to prepare lipidic nanoparticles containing cyclosporine (CyA by the emulsification-diffusion method and to study their physicochemical stability. Glyceryl behenate (Compritol® ATO 888 and lauroyl macrogolglycerides (Gelucire® 44/14 were used as carrier materials. Nanoparticles with good stability were obtained with Gelucire®, while it was difficult to obtain stable systems with Compritol®. Systems with Gelucire® were characterized by particle size, Z-potential, differential scanning calorimetry (DSC, scanning electron microscopy (SEM, entrapment efficiency and in vitro release. Particle size and Z-potential were evaluated for at least three months. With a high CyA content (≥60 mg in Gelucire® SLNs, variations in size were greater and particle size also increased over time in all batches; this effect may have been caused by a probable expulsion of the drug due to the lipid’s partial rearrangement. While the Z-potential decreased 10 mV after three months, this effect may be explained by the superficial properties of the drug that make the molecules to be preferably oriented at the solid-liquid interface, causing a change in the net charge of the particle. SEM confirmed size and shape of the nanoparticles. DSC studies evidenced that CyA affects the lipid structure by a mechanism still unknown

  16. Solid lipid nanoparticles as insulin inhalation carriers for enhanced pulmonary delivery.

    Science.gov (United States)

    Bi, Ru; Shao, Wei; Wang, Qun; Zhang, Na

    2009-02-01

    Growing attentions have been paid to the pulmonary route for systemic delivery of peptide and protein drugs, such as insulin. Advantages of this non-injective route include rapid drug deposition in the target organ, fewer systemic side effects and avoiding first pass metabolism. However, sustained release formulations for pulmonary delivery have not been fully exploited till now. In our study, a novel dry powder inhalation (DPI) system of insulin loaded solid lipid nanoparticles (Ins-SLNs) was investigated for prolonged drug release, improved stability and effective inhalation. Firstly, the drug was incorporated into the lipid carriers for a maximum entrapment efficiency as high as 69.47 +/- 3.27% (n = 3). Secondly, DPI formulation was prepared by spray freeze drying of Ins-SLNs suspension, with optimized lyoprotectant and technique parameters in this procedure. The properties of DPI particles were characterized for their pulmonary delivery potency. Thirdly, the in vivo study of intratracheal instillation of Ins-SLNs to diabetic rats showed prolonged hypoglycemic effect and a relative pharmacological bioavailability of 44.40% could be achieved in the group of 8 IU/kg dosage. These results indicated that SLNs have shown increasing potential as an efficient and non-toxic lipophilic colloidal drug carrier for enhanced pulmonary delivery of insulin.

  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. Pharmacodynamics of piroxicam from novel solid lipid microparticles formulated with homolipids from Bos indicus.

    Science.gov (United States)

    Nnamani, Petra O; Attama, Anthony A; Kenechukwu, Franklin C; Ibezim, Emmanuel C; Adikwu, Michael U

    2013-12-01

    The dissolution of piroxicam is a limiting step in its bioavailability on account of its hydrophobicity. The objective of this research was to formulate novel solid lipid microparticles (SLMs) based on homolipids (admixtures of tallow fat (TF) and Softisan(®) 142 (SFT) templated with Phospholipon(®) 90G (P90G), a heterolipid for the delivery of piroxicam. Lipid matrices consisting of TF and SFT in ratios of 1:1, 1:2 and 2:1 were templated with the heterolipid, P90G and characterized by differential scanning calorimetry (DSC). The SLMs produced by hot homogenization technique using the matrices were characterized in terms of thermal properties, particle size, morphology, drug encapsulation efficiency, stability studies and in vitro diffusion studies. In vivo pharmacodynamic study was performed using egg albumin- induced pedal edema in rats. The results showed that addition of Softisan(®) 142 improved the drug holding capacity of the micellar solution of 2:1 mixture of TF and SFT. The in vitro diffusion of piroxicam from this SLM showed maximum release of 87.53 % and followed non-Fickian diffusion kinetic mechanism. At dose equivalence of 10 mg, piroxicamloaded SLMs showed superior in vivo anti-inflammatory properties at 3 h than Feldene(®) and the pure drug sample. This study has shown that surface-modified SLMs could confer favourable properties with respect to drug release and antiinflammatory activity on SLMs for the delivery of piroxicam, thus encouraging further development of the formulations.

  19. Lyophilized sponges loaded with curcumin solid lipid nanoparticles for buccal delivery: Development and characterization.

    Science.gov (United States)

    Hazzah, Heba A; Farid, Ragwa M; Nasra, Maha M A; El-Massik, Magda A; Abdallah, Ossama Y

    2015-08-15

    This study aimed to prepare and evaluate mucoadhesive sponges as dosage forms for delivering solid lipid nanoparticles. For this purpose curcumin (Cur) was formulated as solid nanoparticles (SLN) using Gelucire 50/13, and polaxomer 407. The prepared CurSLN dispersion was thickened with different mucoadhesive polymers. Different concentrations of glycerol, and mannitol of range (0.25-20%), and (0-1%), respectively were also examined. The formed gel was poured into oblong molds and freeze dried to form mucoadhesive sponge to be applied to the buccal mucosa. The prepared sponges were evaluated for their, in-vivo residence time, in-vitro and in-vivo drug release, and hydration capacity. Surface morphology for the different sponges were examined using SEM. TEM was also carried out for sponge fragments previously dispersed into water. Infrared spectroscopy was conducted to investigate interaction between used ingredients. The results showed that the CurSLN loaded HPMC, and Polycarbophil sponges showed 4, and 15 h in-vivo residence time, respectively, providing a considerable amount of curcumin into saliva. The incorporation of glycerol and mannitol at concentration of 1% provided elegant and flexible sponges. The SEM showed that the deposition of CurSLN differed according to the type of polymer used. TEM confirmed the integrity of liberated CurSLN from sponges. IR spectra showed an interaction between HPMC and poloxamer 407, which affected its behavior as a gelling agent. The obtained results provide an efficient approach for delivering solid lipid nanoparticles in a solid dosage form keeping the nanoparticle characters and integrity. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Buparvaquone loaded solid lipid nanoparticles for targeted delivery in theleriosis

    Directory of Open Access Journals (Sweden)

    Maheshkumar P Soni

    2014-01-01

    Full Text Available Background: Buparvaquone (BPQ, a hydroxynaphthoquinone derivative, has been investigated for the treatment of many infections and is recommended as the gold standard for the treatment of theileriosis. Theileriosis, an intramacrophage infection is localized mainly in reticuloendotheileial system (RES organs. The present study investigates development of solid lipid nanoparticles (SLN of BPQ for targeted delivery to the RES. Materials and Methods: BPQ SLN was prepared using melt method by adding a molten mixture into aqueous Lutrol F68 solution (80°C. Larger batches were prepared up to 6 g of BPQ with GMS: BPQ, 2:1. SLN of designed size were obtained using ultraturrax and high pressure homogenizer. A freeze and thaw study was used to optimize type and concentration of cryoprotectant with Sf: Mean particle size, Si: Initial particle size <1.3. Differential scanning calorimetry (DSC, powder X-ray diffraction (XRD and scanning electron microscope (SEM study was performed on optimized formulation. Formulation was investigated for in vitro serum stability, hemolysis and cell uptake study. Pharmacokinetic and biodistribution study was performed in Holtzman rat. Results: Based on solubility in lipid; glyceryl monostearate (GMS was selected for preparation of BPQ SLN. Batches of BPQ SLN were optimized for average particle size and entrapment efficiency at <100 mg solid content. A combination of Solutol HS-15 and Lutrol F68 at 2% w/v and greater enabled the desired Sf/Si < 1.3. Differential scanning calorimetry and powder X-ray diffraction revealed decrease in crystallinity of BPQ in BPQ SLN while, scanning electron microscope revealed spherical morphology. BPQ SLN revealed good stability at 4°C and 25°C. Low hemolytic potential (<8% and in vitro serum stability up to 5 h was observed. Cytotoxicity of SLN to the U937 cell was low. The macrophage cell line revealed high (52% uptake of BPQ SLN in 1 h suggesting the potential to RES uptake. SLN revealed

  1. Development of fast-release solid catchers for rare isotopes

    Science.gov (United States)

    Nolen, Jerry; Greene, John; Elam, Jeffrey; Mane, Anil; Sampathkumaran, Uma; Winter, Raymond; Hess, David; Mushfiq, Mohammad; Stracener, Daniel; Wiendenhoever, Ingo

    2015-04-01

    Porous solid catchers of rare isotopes are being developed for use at high power heavy ion accelerator facilities such as RIKEN, FRIB, and RISP. Compact solid catchers are complementary to helium gas catchers for parasitic harvesting of rare isotopes in the in-flight separators. They are useful for short lived isotopes for basic nuclear physics research and longer-lived isotopes for off-line applications. Solid catchers can operate effectively with high intensity secondary beams, e.g. >> 1E10 atoms/s with release times as short as 10-100 milliseconds. A new method using a very sensitive and efficient RGA has been commissioned off-line at Argonne and is currently being shipped to Florida State University for in-beam measurements of the release curves using stable beams. The same porous solid catcher technology is also being evaluated for use in targets for the production of medical isotopes such as 211-At. Research supported by the U.S. DOE Office of Nuclear Physics under the SBIR Program and Contract # DE-AC02-06CH11357 and a University of Chicago Comprehensive Cancer Center/ANL Pilot Project.

  2. Investigating the correlation between in vivo absorption and in vitro release of fenofibrate from lipid matrix particles in biorelevant medium.

    Science.gov (United States)

    Borkar, Nrupa; Xia, Dengning; Holm, René; Gan, Yong; Müllertz, Anette; Yang, Mingshi; Mu, Huiling

    2014-01-23

    Lipid matrix particles (LMP) may be used as better carriers for poorly water-soluble drugs than liquid lipid carriers because of reduced drug mobilization in the formulations. However, the digestion process of solid lipid particles and their effect on the absorption of poorly water-soluble drugs are not fully understood. This study aimed at investigating the effect of particle size of LMP on drug release in vitro as well as absorption in vivo in order to get a better understanding on the effect of degradation of lipid particles on drug solubilisation and absorption. Fenofibrate, a model poorly water-soluble drug, was incorporated into LMP in this study using probe ultrasound sonication. The resultant LMP were characterised in terms of particle size, size distribution, zeta potential, entrapment efficiency, in vitro lipolysis and in vivo absorption in rat model. LMP of three different particle sizes i.e. approximately 100 nm, 400 nm, and 10 μm (microparticles) were produced with high entrapment efficiencies. The in vitro lipolysis study showed that the recovery of fenofibrate in the aqueous phase for 100 nm and 400 nm LMP was significantly higher (pmicroparticles>control. In summary, the present study demonstrated the particle size dependence of bioavailability of fenofibrate loaded LMP in rat model which correlates well with the in vitro drug release performed in the biorelevant medium. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Controlled release systems containing solid dispersions: strategies and mechanisms.

    Science.gov (United States)

    Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Park, Jun Bom; Lee, Beom-Jin

    2011-10-01

    In addition to a number of highly soluble drugs, most new chemical entities under development are poorly water-soluble drugs generally characterized by an insufficient dissolution rate and a small absorption window, leading to the low bioavailability. Controlled-release (CR) formulations have several potential advantages over conventional dosage forms, such as providing a uniform and prolonged therapeutic effect to improve patient compliance, reducing the frequency of dosing, minimizing the number of side effects, and reducing the strength of the required dose while increasing the effectiveness of the drug. Solid dispersions (SD) can be used to enhance the dissolution rate of poorly water-soluble drugs and to sustain the drug release by choosing an appropriate carrier. Thus, a CR-SD comprises both functions of SD and CR for poorly water-soluble drugs. Such CR dosage forms containing SD provide an immediately available dose for an immediate action followed by a gradual and continuous release of subsequent doses to maintain the plasma concentration of poorly water-soluble drugs over an extended period of time. This review aims to summarize all currently known aspects of controlled release systems containing solid dispersions, focusing on the preparation methods, mechanisms of action and characterization of physicochemical properties of the system.

  4. Effect of liquid-to-solid lipid ratio on characterizations of flurbiprofen-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for transdermal administration.

    Science.gov (United States)

    Song, Aihua; Zhang, Xiaoshu; Li, Yanting; Mao, Xinjuan; Han, Fei

    2016-08-01

    The aim of this study is to evaluate the effect of liquid-to-solid lipid ratio on properties of flurbiprofen-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), and to clarify the superiority of NLCs over SLNs for transdermal administration. Particle size, zeta potential, drug encapsulation efficiency, in vitro occlusion factor, differential scanning calorimetry, X-ray diffractometry, in vitro percutaneous permeation profile, and stability of SLNs and NLCs were compared. Particle size, zeta potential, drug encapsulation efficiency, in vitro occlusion factor, and in vitro percutaneous permeation amount of the developed NLCs were all 78%, >35, and >240 μg/cm(2), respectively, however, for SLNs were 280 nm, -29.11 mV, 63.2%, 32.54, and 225.9 μg/cm(2), respectively. After 3 months storage at 4 °C and 25 °C, almost no significant differences between the evaluated parameters of NLCs were observed. However, for SLNs, particle size was increased to higher than 300 nm (4 °C and 25 °C), drug encapsulation efficiency was decreased to 51.2 (25 °C), in vitro occlusion factor was also decreased to lower than 25 (4 °C and 25 °C), and the cumulative amount was decreased to 148.9 μg/cm(2) (25 °C) and 184.4 μg/cm(2) (4 °C), respectively. And DSC and XRD studies indicated that not only the crystalline peaks of the encapsulated flurbiprofen disappeared but also obvious difference between samples and bulk Compritol® ATO 888 was seen. It could be concluded that liquid-to-solid lipid ratio has significant impact on the properties of SLNs and NLCs, and NLCs showed better stability than SLNs. Therefore, NLCs might be a better option than SLNs for transdermal administration.

  5. Solid lipid nanoparticles for pulmonary delivery of insulin.

    Science.gov (United States)

    Liu, Jie; Gong, Tao; Fu, Hualin; Wang, Changguang; Wang, Xiuli; Chen, Qian; Zhang, Qin; He, Qin; Zhang, Zhirong

    2008-05-22

    Growing attention has been given to the potential of pulmonary route as an alternative for non-invasive systemic delivery of therapeutic agents. In this study, novel nebulizer-compatible solid lipid nanoparticles (SLNs) for pulmonary drug delivery of insulin were developed by reverse micelle-double emulsion method. The influences of the amount of sodium cholate (SC) and soybean phosphatidylcholine (SPC) on the deposition properties of the nanoparticles were investigated. Under optimal conditions, the entrapment delivery (ED), respirable fraction (RF) and nebulization efficiency (NE) of SLNs could reach 96.53, 82.11 and 63.28%, respectively, and Ins-SLNs remained stable during nebulization. Fasting plasma glucose level was reduced to 39.41% and insulin level was increased to approximately 170 microIU/ml 4h after pulmonary administration of 20 IU/kg Ins-SLNs. A pharmacological bioavailability of 24.33% and a relative bioavailability of 22.33% were obtained using subcutaneous injection as a reference. Incorporating fluorescent-labelled insulin into SLNs, we found that the SLNs were effectively and homogeneously distributed in the lung alveoli. These findings suggested that SLNs could be used as a potential carrier for pulmonary delivery of insulin by improving both in vitro and in vivo stability as well as prolonging hypoglycemic effect, which inevitably resulted in enhanced bioavailability.

  6. Hypericin encapsulated in solid lipid nanoparticles: phototoxicity and photodynamic efficiency.

    Science.gov (United States)

    Lima, Adriel M; Pizzol, Carine Dal; Monteiro, Fabíola B F; Creczynski-Pasa, Tânia B; Andrade, Gislaine P; Ribeiro, Anderson O; Perussi, Janice R

    2013-08-05

    The hydrophobicity of some photosensitizers can induce aggregation in biological systems, which consequently reduces photodynamic activity. The conjugation of photosensitizers with nanocarrier systems can potentially be used to overcome this problem. The objective of this study was to prepare and characterise hypericin-loaded solid lipid nanoparticles (Hy-SLN) for use in photodynamic therapy (PDT). SLN were prepared using the ultrasonication technique, and their physicochemical properties were characterised. The mean particle size was found to be 153 nm, with a low polydispersity index of 0.28. One of the major advantages of the SLN formulation is its high entrapment efficiency (EE%). Hy-SLN showed greater than 80% EE and a drug loading capacity of 5.22% (w/w). To determine the photodynamic efficiency of Hy before and after encapsulation in SLN, the rate constants for the photodecomposition of two (1)O2 trapping reagents, DPBF and AU, were determined. These rate constants exhibited an increase of 60% and 50% for each method, respectively, which is most likely due to an increase in the lifetime of the triplet state caused by the increase in solubility. Hy-SLN presented a 30% increase in cell uptake and a correlated improvement of 26% in cytotoxicity. Thus, all these advantages suggest that Hy-loaded SLN has potential for use in PDT. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Solid lipid nanoparticles as attractive drug vehicles: Composition, properties and therapeutic strategies.

    Science.gov (United States)

    Geszke-Moritz, Małgorzata; Moritz, Michał

    2016-11-01

    This work briefly reviews up-to-date developments in solid lipid nanoparticles (SLNs) as effective nanocolloidal system for drug delivery. It summarizes SLNs in terms of their preparation, surface modification and properties. The application of SLNs as a carrier system enables to improve the therapeutic efficacy of drugs from various therapeutic groups. Present uses of SLNs include cancer therapy, dermatology, bacterial infections, brain targeting and eye disorders among others. The usage of SLNs provides enhanced pharmacokinetic properties and modulated release of drugs. SLN ubiquitous application results from their specific features such as possibility of surface modification, increased permeation through biological barriers, resistance to chemical degradation, possibility of co-delivery of various therapeutic agents or stimuli-responsiveness. This paper will be useful to the scientists working in the domain of SLN-based drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Alendronate Sodium as Enteric Coated Solid Lipid Nanoparticles; Preparation, Optimization, and In Vivo Evaluation to Enhance Its Oral Bioavailability.

    Directory of Open Access Journals (Sweden)

    Khaled Mohamed Hosny

    Full Text Available Treatment of osteoporosis with alendronate sodium has several challenges. The first challenge is the low bioavailability. The second main challenge is side effects, which include oesophageal ulceration. The aim of this research was to reformulate alendronate sodium as enteric coated solid lipid nanoparticles in order to enhance its bioavailability, and preventing the free alendronate sodium from coming into direct contact with the gastrointestinal mucosa, and thereby reducing the possibility of side effects. Enteric coated solid lipid nanoparticles were prepared according to the Box-Behnken design employing Design expert® software, and characterized for size, morphology, and entrapment efficiency. The optimized formula was coated with an Eudragit S100 and evaluated for drug release in acidic and basic media, stability studies and pharmacokinetic evaluations on rabbits. The results indicated that, using Derringer's desirability functional tool for optimization, the highest entrapment efficiency value of 74.3% and the smallest size value of 98 nm were predicted under optimum conditions with a desirability value of 0.917. The optimized nanoparticles released alendronate sodium only at an alkaline pH. The pharmacokinetic evaluation revealed that alendronate sodium bioavailability was enhanced by more than 7.4-fold in rabbits. In conclusion, enteric coated solid lipid nanoparticles is a promising formula for the delivery of alendronate sodium, eliminating its oesophageal side effects and enhancing its bioavailability.

  9. Formulation and characterization of hydrophilic drug diclofenac sodium-loaded solid lipid nanoparticles based on phospholipid complexes technology.

    Science.gov (United States)

    Liu, Dongfei; Chen, Li; Jiang, Sunmin; Zhu, Shuning; Qian, Yong; Wang, Fengzhen; Li, Rui; Xu, Qunwei

    2014-03-01

    To successfully prepare the diclofenac sodium (DS)-loaded solid lipid nanoparticles (SLNs), phospholipid complexes (PCs) technology was applied here to improve the liposolubility of DS. Solid lipid nanoparticles (SLNs) loaded with phospholipid complexes (PCs) were prepared by the modified emulsion/solvent evaporation method. DS could be solubilized effectively in the organic solvents with the existence of phospholipid and apparent partition coefficient of DS in PCs increased significantly. X-ray diffraction analysis suggested that DS in PCs was either molecularly dispersed or in an amorphous form. However, no significant difference was observed between the Fourier transform infrared spectroscopy (FT-IR) spectra of physical mixture and that of PCs. Particles with small sizes, narrow polydispersity indexes and high entrapment efficiencies could be obtained with the addition of PCs. Furthermore, according to the transmission electron microscopy, a core-shell structure was likely to be formed. The presence of PCs caused the change of zeta potential and retarded the drug release of SLNs, which indicated that phospholipid formed multilayers around the solid lipid core of SLNs. Both FT-IR and differential scanning calorimetry analysis also illustrated that some weak interactions between DS and lipid materials might take place during the preparation of SLNs. In conclusion, the model hydrophilic drug-DS can be formulated into the SLNs with the help of PCs.

  10. Lactoferrin bioconjugated solid lipid nanoparticles: a new drug delivery system for potential brain targeting.

    Science.gov (United States)

    Singh, Indu; Swami, Rajan; Pooja, Deep; Jeengar, Manish Kumar; Khan, Wahid; Sistla, Ramakrishna

    2016-01-01

    Delivery of drugs to brain is a subtle task in the therapy of many severe neurological disorders. Solid lipid nanoparticles (SLN) easily diffuse the blood-brain barrier (BBB) due to their lipophilic nature. Furthermore, ligand conjugation on SLN surface enhances the targeting efficiency. Lactoferin (Lf) conjugated SLN system is first time attempted for effective brain targeting in this study. Preparation of Lf-modified docetaxel (DTX)-loaded SLN for proficient delivery of DTX to brain. DTX-loaded SLN were prepared using emulsification and solvent evaporation method and conjugation of Lf on SLN surface (C-SLN) was attained through carbodiimide chemistry. These lipidic nanoparticles were evaluated by DLS, AFM, FTIR, XRD techniques and in vitro release studies. Colloidal stability study was performed in biologically simulated environment (normal saline and serum). These lipidic nanoparticles were further evaluated for its targeting mechanism for uptake in brain tumour cells and brain via receptor saturation studies and distribution studies in brain, respectively. Particle size of lipidic nanoparticles was found to be optimum. Surface morphology (zeta potential, AFM) and surface chemistry (FTIR) confirmed conjugation of Lf on SLN surface. Cytotoxicity studies revealed augmented apoptotic activity of C-SLN than SLN and DTX. Enhanced cytotoxicity was demonstrated by receptor saturation and uptake studies. Brain concentration of DTX was elevated significantly with C-SLN than marketed formulation. It is evident from the cytotoxicity, uptake that SLN has potential to deliver drug to brain than marketed formulation but conjugating Lf on SLN surface (C-SLN) further increased the targeting potential for brain tumour. Moreover, brain distribution studies corroborated the use of C-SLN as a viable vehicle to target drug to brain. Hence, C-SLN was demonstrated to be a promising DTX delivery system to brain as it possessed remarkable biocompatibility, stability and efficacy than

  11. Nanoscale science and engineering forum (706c) design of solid lipid particles with iron oxide quantum dots for the delivery of therapeutic agents

    Science.gov (United States)

    Solid lipid particles provide a method to encapsulate and control the release of drugs in vivo but lack the imaging capability provided by CdS quantum dots. This shortcoming was addressed by combining these two technologies into a model system that uses iron oxide as a non-toxic imaging component in...

  12. Fabrication of dendrimer-releasing lipidic nanoassembly for cancer drug delivery.

    Science.gov (United States)

    Sun, Qihang; Ma, Xinpeng; Zhang, Bo; Zhou, Zhuxian; Jin, Erlei; Shen, Youqing; Van Kirk, Edward A; Murdoch, William J; Radosz, Maciej; Sun, Weilin

    2016-06-24

    An inherent dilemma in the use of nanomedicines for cancer drug delivery is their limited penetration into tumors due to their large size. We have demonstrated that dendrimer/lipid nanoassemblies can solve this problem by means of tumor-triggered disassembly and the release of small (several nanometers) dendrimers to facilitate tumor penetration. Herein, we report a general strategy for the fabrication of nanoassemblies from hydrophobic and hydrophilic dendrimers with phospholipids. Hydrophobic dendrimers could assemble with lipids via hydrophobic interactions, whereas hydrophilic dendrimers could only assemble with lipids in the presence of anionic surfactants via both electrostatic and hydrophobic interactions. The nanoassemblies of hydrophobic dendrimers/lipids were found to be capable of stripping off their lipid layers via fusion with the cell membrane and then intracellular or extracellular release of dendrimers, whereas the nanoassemblies of hydrophilic dendrimers/lipids were internalized via endocytosis and then released their dendrimers inside the cells. Therefore, these dendrimer/lipid nanoassemblies could be used for the delivery of different cancer drugs.

  13. Formulation, characterization and pharmacokinetics of praziquantel-loaded hydrogenated castor oil solid lipid nanoparticles.

    Science.gov (United States)

    Xie, Shuyu; Pan, Baoliang; Wang, Ming; Zhu, Luyan; Wang, Fenghua; Dong, Zhao; Wang, Xiaofang; Zhou, WenZhong

    2010-07-01

    The purpose of this study was to formulate praziquantel (PZQ)-loaded hydrogenated castor oil (HCO) solid lipid nanoparticles (SLN) to enhance the bioavailability and prolong the systemic circulation of the drug. PZQ was encapsulated into HCO nanoparticles by a hot homogenization and ultrasonication method. The physicochemical characteristics of SLN were investigated by optical microscope, scanning electron microscopy and photon correlation spectroscopy. Pharmacokinetics were studied after oral, subcutaneous and intramuscular administration in mice. The diameter, polydispersivity index, zeta potential, encapsulation efficiency and loading capacity of the nanoparticles were 344.0 +/- 15.1 nm, 0.31 +/- 0.08, -16.7 +/- 0.5 mV, 62.17 +/- 6.53% and 12.43 +/- 1.31%, respectively. In vitro release of PZQ-loaded HCO-SLN exhibited an initial burst release followed by a sustained release. SLN increased the bioavailability of PZQ by 14.9-, 16.1- and 2.6-fold, and extended the mean residence time of the drug from 7.6, 6.6 and 8.2 to 95.9, 151.6 and 48.2 h after oral, subcutaneous and intramuscular administration, respectively. The PZQ-loaded HCO-SLN could be a promising formulation to enhance the pharmacological activity of PZQ.

  14. Encapsulation of naproxen in lipid-based matrix microspheres: characterization and release kinetics.

    Science.gov (United States)

    Bhoyar, P K; Morani, D O; Biyani, D M; Umekar, M J; Mahure, J G; Amgaonkar, Y M

    2011-04-01

    The objective of this study was to microencapsulate the anti-inflammatory drug (naproxen) to provide controlled release and minimizing or eliminating local side effect by avoiding the drug release in the upper gastrointestinal track. Naproxen was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using modified melt dispersion (modified congealable disperse phase encapsulation) technique. Effect of various formulation and process variables such as drug-lipid ratio, concentration of modifier, concentration of dispersant, stirring speed, stirring time, temperature of external phase, on evaluatory parameters such as size, entrapment efficiency, and in vitro release of naproxen were studied. The microspheres were characterized for particle size, scanning electron microscopy (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies, for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The drug entrapment efficiency of various batches of microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65% drug release. In vitro drug release from all the batches showed better fitting with the Korsmeyer-Peppas model, indicating the possible mechanism of drug release to be by diffusion and erosion of the lipid matrix.

  15. Influence of encapsulated functional lipids on crystal structure and chemical stability in solid lipid nanoparticles: Towards bioactive-based design of delivery systems.

    Science.gov (United States)

    Salminen, Hanna; Gömmel, Christina; Leuenberger, Bruno H; Weiss, Jochen

    2016-01-01

    We investigated the influence of physicochemical properties of encapsulated functional lipids--vitamin A, β-carotene and ω-3 fish oil--on the structural arrangement of solid lipid nanoparticles (SLN). The relationship between the crystal structure and chemical stability of the incorporated bioactive lipids was evaluated with different emulsifier compositions of a saponin-rich, food-grade Quillaja extract alone or combined with high-melting or low-melting lecithins. The major factors influencing the structural arrangement and chemical stability of functional lipids in solid lipid dispersions were their solubility in the aqueous phase and their crystallization temperature in relation to that of the carrier lipid. The results showed that the stabilization of the α-subcell crystals in the lattice of the carrier lipid is a key parameter for forming stable solid lipid dispersions. This study contributes to a better understanding of SLN as a function of the bioactive lipid. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. 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 

  17. Buparvaquone loaded solid lipid nanoparticles for targeted delivery in theleriosis

    Science.gov (United States)

    Soni, Maheshkumar P.; Shelkar, Nilakash; Gaikwad, Rajiv V.; Vanage, Geeta R.; Samad, Abdul; Devarajan, Padma V.

    2014-01-01

    Background: Buparvaquone (BPQ), a hydroxynaphthoquinone derivative, has been investigated for the treatment of many infections and is recommended as the gold standard for the treatment of theileriosis. Theileriosis, an intramacrophage infection is localized mainly in reticuloendotheileial system (RES) organs. The present study investigates development of solid lipid nanoparticles (SLN) of BPQ for targeted delivery to the RES. Materials and Methods: BPQ SLN was prepared using melt method by adding a molten mixture into aqueous Lutrol F68 solution (80°C). Larger batches were prepared up to 6 g of BPQ with GMS: BPQ, 2:1. SLN of designed size were obtained using ultraturrax and high pressure homogenizer. A freeze and thaw study was used to optimize type and concentration of cryoprotectant with Sf: Mean particle size, Si: Initial particle size Solutol HS-15 and Lutrol F68 at 2% w/v and greater enabled the desired Sf/Si < 1.3. Differential scanning calorimetry and powder X-ray diffraction revealed decrease in crystallinity of BPQ in BPQ SLN while, scanning electron microscope revealed spherical morphology. BPQ SLN revealed good stability at 4°C and 25°C. Low hemolytic potential (<8%) and in vitro serum stability up to 5 h was observed. Cytotoxicity of SLN to the U937 cell was low. The macrophage cell line revealed high (52%) uptake of BPQ SLN in 1 h suggesting the potential to RES uptake. SLN revealed longer circulation and biodistrbution study confirmed high RES uptake (75%) in RES organs like liver lung spleen etc. Conclusion: The high RES uptake suggests BPQ SLN as a promising approach for targeted and improved delivery in theileriosis. PMID:24459400

  18. Cationic solid-lipid nanoparticles can efficiently bind and transfect plasmid DNA

    NARCIS (Netherlands)

    Olbrich, C; Bakowsky, U; Muller, RH; Kneuer, C

    2001-01-01

    The suitability of cationically modified solid-lipid nanoparticles (SLN) as a novel transfection agent was investigated. SLN were produced by hot homogenisation using either Compritol ATO 888 or paraffin as matrix lipid, a mixture of Tween 80 and Span 85 as tenside and either EQ1

  19. Preparation and characterization of ketoprofen-loaded solid lipid nanoparticles made from beeswax and carnauba wax.

    Science.gov (United States)

    Kheradmandnia, Soheila; Vasheghani-Farahani, Ebrahim; Nosrati, Mohsen; Atyabi, Fatemeh

    2010-12-01

    Solid lipid nanoparticles (SLNs) have been proposed as suitable colloidal carriers for delivery of drugs with limited solubility. Ketoprofen as a model drug was incorporated into SLNs prepared from a mixture of beeswax and carnauba wax using Tween 80 and egg lecithin as emulsifiers. The characteristics of the SLNs with various lipid and surfactant composition were investigated. The mean particle size of drug-loaded SLNs decreased upon mixing with Tween 80 and egg lecithin as well as upon increasing total surfactant concentration. SLNs of 75 ± 4 nm with a polydispersity index of 0.2 ± 0.02 were obtained using 1% (vol/vol) mixed surfactant at a ratio of 60:40 Tween 80 to egg lecithin. The zeta potential of these SLNs varied in the range of -15 to -17 (mV), suggesting the presence of similar interface properties. High drug entrapment efficiency of 97% revealed the ability of SLNs to incorporate a poorly water-soluble drug such as ketoprofen. Differential scanning calorimetry thermograms and high-performance liquid chromatographic analysis indicated the stability of nanoparticles with negligible drug leakage after 45 days of storage. It was also found that nanoparticles with more beeswax content in their core exhibited faster drug release as compared with those containing more carnauba wax in their structure. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. New Approach to Solid Lipid Microparticles USING Biocompatible ...

    African Journals Online (AJOL)

    Tallowation refers to the modification of lipid molecules using tallow fat while P90Gylation is the modification of lipid molecules by one or more phospholipid chains. Phospholipon® 90G (P90G) contains about 94.0 % of phosphatidylcholine stabilized with 0.1 % ascorbyl palmitate and is parenterally safe (GRAS) FDA ...

  1. Solid-state fermentation of Mortierella isabellina for lipid production from soybean hull.

    Science.gov (United States)

    Zhang, Jianguo; Hu, Bo

    2012-02-01

    Soybean hull, generated from soybean processing, is a lignocellulosic material with limited industrial applications and little market value. This research is exploring a new application of soybean hull to be converted to fungal lipids for biodiesel production through solid-state fermentation. Mortierella isabellina was selected as the oil producer because of its high lipid content at low C/N ratio. Several cultivation factors were investigated, including moisture content, inoculums size, fungal spore age, and nutrient supplements, in an attempt to enhance the lipid production of the solid-state fermentation process. The results showed that lipid production with the increase of the moisture content and the spore age, while decreased as the size of inoculums increased. Nutrients addition (KH₂PO₄ 1.2 mg and MgSO₄ 0.6 mg/g soybean hull) improved the lipid production. The total final lipid reached 47.9 mg lipid from 1 g soybean hull after the conversion, 3.3-fold higher than initial lipid reserve in the soybean hull. The fatty acid profile analysis indicated that fatty acid content consisted of 30.0% of total lipid, and 80.4% of total fatty acid was C16 and C18. Therefore, lipid production from soybean hull is a possible option to enable soybean hull as a new resource for biodiesel production and to enhance the overall oil production from soybeans.

  2. Production of solid lipid submicron particles for protein delivery using a novel supercritical gas-assisted melting atomization process.

    Science.gov (United States)

    Salmaso, Stefano; Elvassore, Nicola; Bertucco, Alberto; Caliceti, Paolo

    2009-02-01

    A supercritical carbon dioxide micronization technique based on gas-assisted melting atomization has been designed to prepare protein-loaded solid lipid submicron particles. The supercritical process was applied to homogeneous dispersions of insulin in lipid mixtures: (1) tristearin, Tween-80, phosphatidylcholine and 5 kDa PEG (1:0.1:0.9:1 and 1:0.1:0.9:2 weight ratio); and (2) tristearin, dioctyl sulfosuccinate and phosphatidylcholine (1:1:0.5 weight ratio). Optimized process conditions yielded dry nonagglomerated powders with high product recovery (70%, w/w). Dynamic light scattering and transmission electron microscopy showed that two size fractions of particles, with 80-120 and 200-400 nm diameters, were produced. In all final products, dimethylsulfoxide used to prepare the insulin/lipid mixture was below 20 ppm. Protein encapsulation efficiency increased up to 80% as the DMSO content in the insulin/lipid mixture increased. Compared to the particles without PEG, the polymer-containing particles dispersed rapidly in water, and the dispersions were more stable under centrifugation as less than 20% of suspended particles precipitated after extensive centrifugation. In vitro, the protein was slowly released from the formulation without PEG, while a burst and faster release were obtained from the formulations containing PEG. Subcutaneous injection to diabetic mice of insulin extracted from the particles showed that the supercritical process did not impair the protein hypoglycemic activity.

  3. Evaluation of Gentamicin-Entrapped Solid Lipid Microparticles ...

    African Journals Online (AJOL)

    microbial infections, is limited by poor absorption, low bioavailability ... engineering of lipid drug delivery systems. (LBDDS) ... based SLMs), these problems could be surmounted. ..... addition to the burst effect, may also be related to high rate ...

  4. Solid lipid nanoparticles loaded with edaravone for inner ear protection after noise exposure.

    Science.gov (United States)

    Gao, Gang; Liu, Ya; Zhou, Chang-Hua; Jiang, Ping; Sun, Jian-Jun

    2015-01-20

    Antioxidants and the duration of treatment after noise exposure on hearing recovery are important. We investigated the protective effects of an antioxidant substance, edaravone, and its slow-release dosage form, edaravone solid lipid nanoparticles (SLNs), in steady noise-exposed guinea pigs. SLNs loaded with edaravone were produced by an ultrasound technique. Edaravone solution or edaravone SLNs were administered by intratympanic or intravenous injection after the 1 st day of noise exposure. Guinea pigs were exposed to 110 dB sound pressure level (SPL) noise, centered at 0.25-4.0 kHz, for 4 days at 2 h/d. After noise exposure, the guinea pigs underwent auditory brainstem response (ABR) threshold measurements, reactive oxygen species (ROS) were detected in their cochleas with electron spin resonance (ESR), and outer hair cells (OHCs) were counted with silvernitrate (AgNO 3 ) staining at 1, 4, and 6 days. The ultrasound technique was able to prepare adequate edaravone SLNs with a mean particle size of 93.6 nm and entrapment efficiency of 76.7%. Acoustic stress-induced ROS formation and edaravone exerted a protective effect on the cochlea. Comparisons of hearing thresholds and ROS changes in different animal groups showed that the threshold shift and ROS generation were significantly lower in treated animals than in those without treatment, especially in the edaravone SLN intratympanic injection group. Edaravone SLNs show noticeable slow-release effects and have certain protective effects against noise-induced hearing loss (NIHL).

  5. Microwave-assisted microemulsion technique for production of miconazole nitrate- and econazole nitrate-loaded solid lipid nanoparticles.

    Science.gov (United States)

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

    2017-08-01

    The microwave-assisted production of solid lipid nanoparticles (SLNs) is a novel technique reported recently by our group. The small particle size, solid nature and use of physiologically well-tolerated lipid materials make SLNs an interesting and potentially efficacious drug carrier. The main purpose of this research work was to investigate the suitability of microwave-assisted microemulsion technique to encapsulate selected ionic drug substances such as miconazole nitrate and econazole nitrate. The microwave-produced SLNs had a small size (250-300nm), low polydispersity (microwave-produced SLNs. Data fitting of drug release data revealed that the release of both drugs from microwave-produced SLNs was governed by non-Fickian diffusion indicating that drug release was both diffusion- and dissolution- controlled. Anti-fungal efficacy of drug-loaded SLNs was evaluated on C. albicans. The cell viability studies showed that cytotoxicity of SLNs was concentration-dependent. These encouraging results suggest that the microwave-assisted procedure is suitable for encapsulation of ionic drugs and that microwave-produced SLNs can act as potential carriers of antifungal drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Applications of lipid nanocarriers for solid tumors therapy: literature review; Aplicacoes das nanoparticulas lipidicas no tratamento de tumores solidos: revisao de literatura

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Lidiane Correia de; Souza, Leonardo Gomes; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephania Fleury [Universidade Federal de Goias (UFG), Goiania, GO (Brazil). Fac. de Farmacia; Taveira, Eliseu Jose Fleury, E-mail: stephaniafleury@gmail.com [Hospital Erasto Gaertner, Curitiba, PR (Brazil). Oncologia Clinica

    2012-07-01

    Introduction: Lipid nanocarriers are systems used to target drugs to its site of action and have attracted attention of the scientific community because they are biocompatible and biodegradable. These systems can target drugs to solid tumors, providing sustained drug release in the site of action, thus increasing the utility of the antineoplastic chemotherapy. Objective: To review the available literature on in vivo experiments with lipid nanocarriers containing cytotoxic drugs for solid tumors treatment. Method: A search study was carried out in Pubmed{sup R} database from 2007 to 2011, with subject descriptors: liposomes, lipid nanoparticles, cancer and in vivo, with the boolean operator 'and' among them, in English. Results: 1,595 papers related to the use of liposomes and 77 related to lipid nanoparticles were found. Few studies reported in vivo experiments with lipid nanoparticles (28 papers) compared to liposomes (472 papers), since liposomes were developed two decades before lipid nanoparticles. Four liposomal medicines have already been approved and are used in the clinic while only one medicine containing lipid nanoparticles is in phase I of clinical studies. Conclusion: The number of papers related to the use of nanotechnology for cancer treatment is increasing rapidly, making important to know the different kinds of nanocarriers and, especially, those which are already used in the clinic. There are only few clinical studies on lipid nanocarriers; however, these systems present an enormous potential to improve the clinical practice in oncology. (author)

  7. Preparation and characterization of etoricoxib solid dispersions using lipid carriers by spray drying technique

    OpenAIRE

    Chauhan, Bhaskar; Shimpi, Shyam; Paradkar, Anant

    2005-01-01

    The basic objectives of this study were to prepare and characterize solid dispersions of poorly water-soluble drug etoricoxib using lipid carriers by spray drying technique. The properties of solid dispersions were studied by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), differential scanning calorimetry (DSC), hotstage microscopy (HSM), radiograph powder diffraction (XRPD), and dissolution studies. The absence of etoricoxib peaks in XRPD profiles of solid dispersions ...

  8. Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Ji P

    2016-03-01

    Full Text Available Peng Ji, Tong Yu, Ying Liu, Jie Jiang, Jie Xu, Ying Zhao, Yanna Hao, Yang Qiu, Wenming Zhao, Chao WuCollege of Pharmacy, Liaoning Medical University, Jinzhou, Liaoning Province, People’s Republic of ChinaAbstract: Naringenin (NRG, a flavonoid compound, had been reported to exhibit extensive pharmacological effects, but its water solubility and oral bioavailability are only ~46±6 µg/mL and 5.8%, respectively. The purpose of this study is to design and develop NRG-loaded solid lipid nanoparticles (NRG-SLNs to provide prolonged and sustained drug release, with improved stability, involving nontoxic nanocarriers, and increase the bioavailability by means of pulmonary administration. Initially, a group contribution method was used to screen the best solid lipid matrix for the preparation of SLNs. NRG-SLNs were prepared by an emulsification and low-temperature solidification method and optimized using an orthogonal experiment approach. The morphology was examined by transmission electron microscopy, and the particle size and zeta potential were determined by photon correlation spectroscopy. The total drug content of NRG-SLNs was measured by high-performance liquid chromatography, and the encapsulation efficiency (EE was determined by Sephadex gel-50 chromatography and high-performance liquid chromatography. The in vitro NRG release studies were carried out using a dialysis bag. The best cryoprotectant to prepare NRG-SLN lyophilized powder for future structural characterization was selected using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The short-term stability, 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT assay, cellular uptake, and pharmacokinetics in rats were studied after pulmonary administration of NRG-SLN lyophilized powder. Glycerol monostearate was selected to prepare SLNs, and the optimal formulation of NRG-SLNs was spherical in shape, with a particle

  9. Biowaiver monographs for immediate release solid oral dosage forms: efavirenz.

    Science.gov (United States)

    Cristofoletti, Rodrigo; Nair, Anita; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Dressman, Jennifer B

    2013-02-01

    Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence testing for the approval of immediate-release (IR) solid oral dosage forms containing efavirenz as the only active pharmaceutical ingredient (API) are reviewed. Because of lack of conclusive data about efavirenz's permeability and its failure to comply with the "high solubility" criteria according to the Biopharmaceutics Classification System (BCS), the API can be classified as BCS Class II/IV. In line with the solubility characteristics, the innovator product does not meet the dissolution criteria for a "rapidly dissolving product." Furthermore, product variations containing commonly used excipients or in the manufacturing process have been reported to impact the rate and extent of efavirenz absorption. Despite its wide therapeutic index, subtherapeutic levels of efavirenz can lead to treatment failure and also facilitate the emergence of efavirenz-resistant mutants. For all these reasons, a biowaiver for IR solid oral dosage forms containing efavirenz as the sole API is not scientifically justified for reformulated or multisource drug products. Copyright © 2012 Wiley Periodicals, Inc.

  10. Iron release from ferritin and lipid peroxidation by radiolytically generated reducing radicals

    International Nuclear Information System (INIS)

    Reif, D.W.; Schubert, J.; Aust, S.D.

    1988-01-01

    Iron is involved in the formation of oxidants capable of damaging membranes, protein, and DNA. Using 137 Cs gamma radiation, we investigated the release of iron from ferritin and concomitant lipid peroxidation by radiolytically generated reducing radicals, superoxide and the carbon dioxide anion radical. Both radicals released iron from ferritin with similar efficiencies and iron mobilization from ferritin required an iron chelator. Radiolytically generated superoxide anion resulted in peroxidation of phospholipid liposomes as measured by malondialdehyde formation only when ferritin was included as an iron source and the released iron was found to be chelated by the phospholipid liposomes

  11. Temperature-controlled continuous production of all-trans retinoic acid-loaded solid lipid nanoparticles using static mixers

    Science.gov (United States)

    Shao, Wenyao; Yan, Mengwen; Chen, Tingting; Chen, Yuqing; Xiao, Zongyuan

    2017-04-01

    This work aims to develop a temperature-controlled continuous solvent emulsification-diffusion process to synthesize all-trans retinoic acid (ATRA)-loaded solid lipid nanoparticles (SLNs) using static mixers. ATRA-loaded SLNs of around 200 nm were obtained when the flow rates of the organic and aqueous phases were 50 ml min-1 and 500 ml min-1, respectively. It was found that the lipid concentration played a dominant role in the size of the obtained SLNs, and higher drug concentration resulted in relatively low entrapment efficiency. The encapsulation of ATRA in the SLNs was effective in improving its stability according to the photo-degradation test. The in vitro release of SLN was slow without an initial burst. This study demonstrates that the solvent emulsification-diffusion technique with static mixing is an effective method of producing SLNs, and could easily be scaled up for industrial applications. Highlights Higher lipid concentration leads to larger SLNs. SLN transformation occurs due to Ostwald ripening. The ATRA-loaded SLNs around 200 nm were successfully produced with static mixers. ATRA-loaded SLNs show better stability towards sunlight. ATRA in SLNs exhibited a relatively slow release rate without a significant initial burst.

  12. Effect of formulation variables on insulin localisation within solid lipid nanoparticles

    OpenAIRE

    Thong, Li Ming

    2016-01-01

    There has been a lot of interest on solid lipid nanoparticles (SLNs) as these colloidal submicron drug dosage forms present a promising frontier in drug delivery. It is possible to incorporate susceptible drugs such as protein intended for oral delivery. Here, we aim to develop an oral delivery system based on SLNs to deliver the peptide hormone, insulin using the double emulsion (W/O/W) solvent evaporation technique for formulating the SLNs. The choice of lipids was carefully selected to inc...

  13. [Preparation of Oenothera biennis Oil Solid Lipid Nanoparticles Based on Microemulsion Technique].

    Science.gov (United States)

    Piao, Lin-mei; Jin, Yong; Cui, Yan-lin; Yin, Shou-yu

    2015-06-01

    To study the preparation of Oenothera biennis oil solid lipid nanoparticles and its quality evaluation. The solid lipid nanoparticles were prepared by microemulsion technique. The optimum condition was performed based on the orthogonal design to examine the entrapment efficiency, the mean diameter of the particles and so on. The optimal preparation of Oenothera biennis oil solid lipid nanoparticles was as follows: Oenothera biennis dosage 300 mg, glycerol monostearate-Oenothera biennis (2: 3), Oenothera biennis -RH/40/PEG-400 (1: 2), RH-40/PEG-400 (1: 2). The resulting nanoparticles average encapsulation efficiency was (89.89 ± 0.71)%, the average particle size was 44.43 ± 0.08 nm, and the Zeta potential was 64.72 ± 1.24 mV. The preparation process is simple, stable and feasible.

  14. Biowaiver monographs for immediate release solid oral dosage forms: piroxicam.

    Science.gov (United States)

    Shohin, Igor E; Kulinich, Julia I; Ramenskaya, Galina V; Abrahamsson, Bertil; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Groot, D W; Barends, Dirk M; Dressman, Jennifer B

    2014-02-01

    Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing piroxicam in the free acid form are reviewed. Piroxicam solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA), and corresponding dissolution data are taken into consideration. The available data suggest that according to the current biopharmaceutics classification system (BCS) and all current guidances, piroxicam would be assigned to BCS Class II. The extent of piroxicam absorption seems not to depend on manufacturing conditions or excipients, so the risk of bioinequivalence in terms of area under the curve (AUC) is very low, but the rate of absorption (i.e., BE in terms of Cmax ) can be affected by the formulation. Current in vitro dissolution methods may not always reflect differences in terms of Cmax for BCS Class II weak acids; however, minor differences in absorption rate of piroxicam would not subject the patient to unacceptable risks: as piroxicam products may be taken before or after meals, the rate of absorption cannot be considered crucial to drug action. Therefore, a biowaiver for IR piroxicam solid oral dosage form is considered feasible, provided that (a) the test product contains only excipients, which are also present in IR solid oral drug products containing piroxicam, which have been approved in ICH or associated countries, for instance, those presented in Table 3 of this paper; (b) both the test and comparator drug products dissolve 85% in 30 min or less at pH 1.2, 4.5, and 6.8; and (c) the test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. When not all of these conditions can be fulfilled, BE of the products should be established in vivo. © 2013 Wiley Periodicals, Inc. and the

  15. Preparation, characterization, and optimization of altretamine-loaded solid lipid nanoparticles using Box-Behnken design and response surface methodology.

    Science.gov (United States)

    Gidwani, Bina; Vyas, Amber

    2016-01-01

    The objective of the present study was to prepare solid lipid nanoparticles (SLNs) of altretamine (ALT) by the hot homogenization and ultrasonication method. The study was conducted using the Box-Behnken design (BBD), with a 3(3) design and a total of 17 experimental runs, performed in combination with response surface methodology (RSM). The SLNs were evaluated for mean particle size, entrapment efficiency, and drug-loading. The optimized formulation, with a desirability factor of 0.92, was selected and characterized. In vitro release studies showed a biphasic release pattern from the SLNs for up to 24 h. The results of % EE (93.21 ± 1.5), %DL (1.15 ± 0.6), and mean diameter of (100.6 ± 2.1) nm, were very close to the predicted values.

  16. Square Wave Voltammetry: An Alternative Technique to Determinate Piroxicam Release Profiles from Nanostructured Lipid Carriers.

    Science.gov (United States)

    Otarola, Jessica; Garrido, Mariano; Correa, N Mariano; Molina, Patricia G

    2016-08-04

    A new, simple, and fast electrochemical (EC) method has been developed to determine the release profile of piroxicam, a nonsteroidal anti-inflammatory drug, loaded in a drug delivery system based on nanostructured lipid carriers (NLCs). For the first time, the samples were analyzed by using square wave voltammetry, a sensitive EC technique. The piroxicam EC responses allow us to propose a model that explains the experimental results and to subsequently determine the amount of drug loaded into the NLCs formulation as a function of time. In vitro drug release studies showed prolonged drug release (up to 5 days), releasing 60 % of the incorporated drug. The proposed method is a promising and stable alternative for the study of different drug delivery systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Solid Lipid Nanoparticles Loaded with Edaravone for Inner Ear Protection After Noise Exposure

    Directory of Open Access Journals (Sweden)

    Gang Gao

    2015-01-01

    Full Text Available Background: Antioxidants and the duration of treatment after noise exposure on hearing recovery are important. We investigated the protective effects of an antioxidant substance, edaravone, and its slow-release dosage form, edaravone solid lipid nanoparticles (SLNs, in steady noise-exposed guinea pigs. Methods: SLNs loaded with edaravone were produced by an ultrasound technique. Edaravone solution or edaravone SLNs were administered by intratympanic or intravenous injection after the 1 st day of noise exposure. Guinea pigs were exposed to 110 dB sound pressure level (SPL noise, centered at 0.25-4.0 kHz, for 4 days at 2 h/d. After noise exposure, the guinea pigs underwent auditory brainstem response (ABR threshold measurements, reactive oxygen species (ROS were detected in their cochleas with electron spin resonance (ESR, and outer hair cells (OHCs were counted with silvernitrate (AgNO 3 staining at 1, 4, and 6 days. Results: The ultrasound technique was able to prepare adequate edaravone SLNs with a mean particle size of 93.6 nm and entrapment efficiency of 76.7%. Acoustic stress-induced ROS formation and edaravone exerted a protective effect on the cochlea. Comparisons of hearing thresholds and ROS changes in different animal groups showed that the threshold shift and ROS generation were significantly lower in treated animals than in those without treatment, especially in the edaravone SLN intratympanic injection group. Conclusions: Edaravone SLNs show noticeable slow-release effects and have certain protective effects against noise-induced hearing loss (NIHL.

  18. Preliminary Studies on Solid Lipid Microparticles of Loratadine for ...

    African Journals Online (AJOL)

    HP

    side effects of drugs reported via oral administration can be ... emulsion obtained was kept under the water flowing from a tap for ... through S&S5893 blue ribbon paper (2 µm pore ..... r = correlation coefficient; n = diffusion exponent of release profile (slope). Best fits were .... physical stability and particle matrix structure. Int J.

  19. A novel and alternative approach to controlled release drug delivery system based on solid dispersion technique

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Giri

    2012-12-01

    Full Text Available The solid dispersion method was originally used to improve the dissolution properties and the bioavailability of poorly water soluble drugs by dispersing them into water soluble carriers. In addition to the above, dissolution retardation through solid dispersion technique using water insoluble and water swellable polymer for the development of controlled release dosage forms has become a field of interest in recent years. Development of controlled release solid dispersion has a great advantage for bypassing the risk of a burst release of drug; since the structure of the solid dispersion is monolithic where drug molecules homogeneously disperse. Despite the remarkable potential and extensive research being conducted on controlled release solid dispersion system, commercialization and large scale production are limited. The author expects that recent technological advances may overcome the existing limitations and facilitate the commercial utilization of the techniques for manufacture of controlled release solid dispersions. This article begins with an overview of the different carriers being used for the preparation of controlled release solid dispersion and also different techniques being used for the purpose. Kinetics of drug release from these controlled release solid dispersions and the relevant mathematical modeling have also been reviewed in this manuscript.

  20. Solid lipid nanoparticles loaded with insulin by sodium cholate-phosphatidylcholine-based mixed micelles: preparation and characterization.

    Science.gov (United States)

    Liu, Jie; Gong, Tao; Wang, Changguang; Zhong, Zhirong; Zhang, Zhirong

    2007-08-01

    Solid lipid nanoparticles (SLNs) loaded with insulin-mixed micelles (Ins-MMs) were prepared by a novel reverse micelle-double emulsion method, in which sodium cholate (SC) and soybean phosphatidylcholine (SPC) were employed to improve the liposolubility of insulin, and the mixture of stearic acid and palmitic acid were employed to prepare insulin loaded solid lipid nanoparticles (Ins-MM-SLNs). Some of the formulation parameters were optimized to obtain high quality nanoparticles. The particle size and zeta potential measured by photon correlation spectroscopy (PCS) were 114.7+/-4.68 nm and -51.36+/-2.04 mV, respectively. Nanospheres observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed extremely spherical shape. The entrapment efficiency (EE%) and drug loading capacity (DL%) determined with high performance liquid chromatogram (HPLC) by modified ultracentrifuge method were 97.78+/-0.37% and 18.92+/-0.07%, respectively. Differential scanning calorimetry (DSC) of Ins-MM-SLNs indicated no tendency of recrystallisation. The core-shell drug loading pattern of the SLNs was confirmed by fluorescence spectra and polyacrylamide gel electrophoresis (PAGE) which also proved the integrity of insulin after being incorporated into lipid carrier. The drug release behavior was studied by in situ and externally sink method and the release pattern of drug was found to follow Weibull and Higuchi equations. Results of stability evaluation showed a relatively long-term stability after storage at 4 degrees C for 6 months. In conclusion, SLNs with small particle size, excellent physical stability, high entrapment efficiency, good loading capacity for protein drug can be produced by this novel reverse micelle-double emulsion method in present study.

  1. Natural lipid extracts and biomembrane-mimicking lipid compositions are disposed to form nonlamellar phases, and they release DNA from lipoplexes most efficiently

    Energy Technology Data Exchange (ETDEWEB)

    Koynova, Rumiana; MacDonald, Robert C. (NWU)

    2010-01-18

    A viewpoint now emerging is that a critical factor in lipid-mediated transfection (lipofection) is the structural evolution of lipoplexes upon interacting and mixing with cellular lipids. Here we report our finding that lipid mixtures mimicking biomembrane lipid compositions are superior to pure anionic liposomes in their ability to release DNA from lipoplexes (cationic lipid/DNA complexes), even though they have a much lower negative charge density (and thus lower capacity to neutralize the positive charge of the lipoplex lipids). Flow fluorometry revealed that the portion of DNA released after a 30-min incubation of the cationic O-ethylphosphatidylcholine lipoplexes with the anionic phosphatidylserine or phosphatidylglycerol was 19% and 37%, respectively, whereas a mixture mimicking biomembranes (MM: phosphatidylcholine/phosphatidylethanolamine/phosphatidylserine /cholesterol 45:20:20:15 w/w) and polar lipid extract from bovine liver released 62% and 74%, respectively, of the DNA content. A possible reason for this superior power in releasing DNA by the natural lipid mixtures was suggested by structural experiments: while pure anionic lipids typically form lamellae, the natural lipid mixtures exhibited a surprising predilection to form nonlamellar phases. Thus, the MM mixture arranged into lamellar arrays at physiological temperature, but began to convert to the hexagonal phase at a slightly higher temperature, {approx} 40-45 C. A propensity to form nonlamellar phases (hexagonal, cubic, micellar) at close to physiological temperatures was also found with the lipid extracts from natural tissues (from bovine liver, brain, and heart). This result reveals that electrostatic interactions are only one of the factors involved in lipid-mediated DNA delivery. The tendency of lipid bilayers to form nonlamellar phases has been described in terms of bilayer 'frustration' which imposes a nonzero intrinsic curvature of the two opposing monolayers. Because the stored

  2. 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.

  3. Growth and lipid production of Umbelopsis isabellina on a solid substrate - Mechanistic modeling and validation

    NARCIS (Netherlands)

    Meeuwse, P.; Klok, A.J.; Haemers, S.; Tramper, J.; Rinzema, A.

    2012-01-01

    Microbial lipids are an interesting feedstock for biodiesel. Their production from agricultural waste streams by fungi cultivated in solid-state fermentation may be attractive, but the yield of this process is still quite low. In this article, a mechanistic model is presented that describes growth,

  4. Controlling Release of Integral Lipid Nanoparticles Based on Osmotic Pump Technology.

    Science.gov (United States)

    Tian, Zhiqiang; Yu, Qin; Xie, Yunchang; Li, Fengqian; Lu, Yi; Dong, Xiaochun; Zhao, Weili; Qi, Jianping; Wu, Wei

    2016-08-01

    To achieve controlled release of integral nanoparticles by the osmotic pump strategy using nanostructured lipid carriers (NLCs) as model nanoparticles. NLCs was prepared by a hot-homogenization method, transformed into powder by lyophilization, and formulated into osmotic pump tablets (OPTs). Release of integral NLCs was visualized by live imaging after labeling with a water-quenching fluorescent probe. Effects of formulation variables on in vitro release characteristics were evaluated by measuring the model drug fenofibrate. Pharmacokinetics were studied in beagle dogs using the core tablet and a micronized fenofibrate formulation as references. NLCs are released through the release orifices of the OPTs as integral nanoparticles. Near zero-order kinetics can be achieved by optimizing the influencing variables. After oral administration, decreased C max and steady drug levels for as long as over 24 h are observed. NLC-OPTs show an oral bioavailability of the model drug fenofibrate similar to that of the core tablets, which is about 1.75 folds that of a fast-release formulation. Controlled release of integral NLCs is achieved by the osmotic pump strategy.

  5. Preparation of ultra-fine powders from polysaccharide-coated solid lipid nanoparticles and nanostructured lipid carriers by innovative nano spray drying technology.

    Science.gov (United States)

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

    2016-09-10

    In this study, five polysaccharides were applied as natural polymeric coating materials to prepare solid lipid nanoparticles (SLN) and nanostructure lipid carriers (NLC), and then the obtained lipid colloidal particles were transformed to solid powders by the innovative nano spray drying technology. The feasibility and suitability of this new technology to generate ultra-fine lipid powder particles were evaluated and the formulation was optimized. The spray dried SLN powder exhibited the aggregated and irregular shape and dimension, but small, uniform, well-separated spherical powder particles of was obtained from NLC. The optimal formulation of NLC was prepared by a 20-30% oleic acid content with carrageenan or pectin as coating material. Therefore, nano spray drying technology has a potential application to produce uniform, spherical, and sub-microscale lipid powder particles when the formulation of lipid delivery system is appropriately designed. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. 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

  7. Solid lipid nanoparticles as promising tool for intraocular tobramycin delivery: Pharmacokinetic studies on rabbits.

    Science.gov (United States)

    Chetoni, Patrizia; Burgalassi, Susi; Monti, Daniela; Tampucci, Silvia; Tullio, Vivian; Cuffini, Anna Maria; Muntoni, Elisabetta; Spagnolo, Rita; Zara, Gian Paolo; Cavalli, Roberta

    2016-12-01

    Eye drops are widely accepted as formulations for targeting the anterior segment notwithstanding their limitations in terms of bioavailability. The unique structure of the eye requires specially-designed formulations able to favor the pharmacokinetic profile of administered drugs, mainly minimizing the influence of ocular barriers. Nanotechnology-based delivery systems lead to significant technological and therapeutical advantages in ophthalmic therapy. The aim of the present study was to determine whether tobramycin as ion-pair incorporated in mucoadhesive Solid Lipid Nanoparticles (SLN) reaches the inner parts of the eye favoring drug activity. After technological characterization of the tobramycin entrapped SLN formulation (Tobra-SLN), a pharmacokinetic study in rabbits after topical instillation and intravenous administration of the formulation has been carried out. In addition, the intracellular activity of Tobra-SLN formulation against phagocytosed Pseudomonas aeruginosa was investigated. The SLN were spherical in shape, and showed a hydrodynamic diameter of about 80nm, a negative zeta potential (-25.7mV) with a polydispersity index of 0.15, representative of a colloidal dispersion with high quality, characterized by an unimodal relatively narrow size distribution. As demonstrated by FTIR and DSC, tobramycin ion-pair could be concentrated into lipid inner core of SLN, without interaction with the stearic acid, thus promoting a slow and constant drug release profile in the dissolution medium. Surprisingly, the drug concentration was significantly higher in all ocular tissues after ocular and intravenous administration of Tobra-SLN formulation with respect to reference formulations and only Tobra-SLN allowed the penetration of drug into retina. Furthermore, the use of Tobra-SLN resulted in both higher intraphagocytic antibiotic concentrations in polymorphonuclear granulocytes and greater bactericidal activity against intracellular Pseudomonas aeruginosa

  8. Optimization of methazolamide-loaded solid lipid nanoparticles for ophthalmic delivery using Box-Behnken design.

    Science.gov (United States)

    Wang, Fengzhen; Chen, Li; Jiang, Sunmin; He, Jun; Zhang, Xiumei; Peng, Jin; Xu, Qunwei; Li, Rui

    2014-09-01

    The purpose of the present study was to optimize methazolamide (MTZ)-loaded solid lipid nanoparticles (SLNs) which were used as topical eye drops by evaluating the relationship between design factors and experimental data. A three factor, three-level Box-Behnken design (BBD) was used for the optimization procedure, choosing the amount of GMS, the amount of phospholipid, the concentration of surfactant as the independent variables. The chosen dependent variables were entrapment efficiency, dosage loading, and particle size. The generated polynomial equations and response surface plots were used to relate the dependent and independent variables. The optimal nanoparticles were formulated with 100 mg GMS, 150 mg phospholipid, and 1% Tween80 and PEG 400 (1:1, w/v). A new formulation was prepared according to these levels. The observed responses were close to the predicted values of the optimized formulation. The particle size was 197.8 ± 4.9 nm. The polydispersity index of particle size was 0.239 ± 0.01 and the zeta potential was 32.7 ± 2.6 mV. The entrapment efficiency and dosage loading were about 68.39% and 2.49%, respectively. Fourier transform infrared spectroscopy (FT-IR) study indicated that the drug was entrapped in nanoparticles. The optimized formulation showed a sustained release followed the Peppas model. MTZ-SLNs showed significant prolonged decreasing intraocular pressure effect comparing with MTZ solution in vivo pharmacodynamics studies. The results of acute eye irritation study indicated that MTZ-SLNs and AZOPT both had no eye irritation. Furthermore, the MTZ-SLNs were suitable to be stored at low temperature (4 °C).

  9. Effect of Lipid Composition on In Vitro Release and Skin Deposition of Curcumin Encapsulated Liposomes

    Directory of Open Access Journals (Sweden)

    Geethi Pamunuwa

    2016-01-01

    Full Text Available Liposomal encapsulation improves numerous physiochemical and biological properties of curcumin. The aim of this work was to impart slow release and skin delivery of curcumin via liposomal encapsulation. Liposomes were made using egg yolk phosphatidylcholine as the staple lipid while incorporating polysorbate 80 and stearylamine to prepare hybrid liposomes and positively charged liposomes, respectively. Negatively charged liposomes exhibited the highest encapsulation efficiencies (87.8±4.3% and loading capacities (3.4±0.2%. The sizes of all formulations were about 250 nm, while stearylamine increased the polydispersity index. Positively charged liposomes showed lower degradation temperatures than negatively charged liposomes by 10–15°C, attributable to the presence of stearylamine. The melting temperatures of positively charged liposomes (40–50°C were much higher than those of negatively charged liposomes (14-15°C, which may have affected release and skin deposition behavior of liposomes. The positively charged liposomes exhibited the slowest release of curcumin in phosphate buffered saline (pH 6.8 and the release profiles of all liposomal formulations conformed to the Gompertz model. The negatively charged liposomes facilitated the highest skin deposition of curcumin as revealed by studies conducted using excised pig ear skin. Concisely, positively and negatively charged liposomes were optimal for slow release and skin deposition of curcumin, respectively.

  10. Release of non-methane organic compounds during simulated landfilling of aerobically pretreated municipal solid waste.

    Science.gov (United States)

    Zhang, Yuanyuan; Yue, Dongbei; Liu, Jianguo; Lu, Peng; Wang, Ying; Liu, Jing; Nie, Yongfeng

    2012-06-30

    Characteristics of non-methane organic compounds (NMOCs) emissions during the anaerobic decomposition of untreated (APD-0) and four aerobically pretreated (APD-20, APD-39, APD-49, and APD-63) samples of municipal solid waste (MSW) were investigated in laboratory. The cumulative mass of the NMOCs of APD-20, APD-39, APD-49, and APD-63 accounted for 15%, 9%, 16%, and 15% of that of APD-0, respectively. The intensities of the NMOC emissions calculated by dividing the cumulative NMOC emissions by the quantities of organic matter removed (Q(VS)) decreased from 4.1 mg/kg Q(VS) for APD-0 to 0.8-3.4 mg/kg Q(VS) for aerobically pretreated MSW. The lipid and starch contents might have significant impact on the intensity of the NMOC emissions. Alkanes dominated the NMOCs released from the aerobically pretreated MSW, while oxygenated compounds were the chief component of the NMOCs generated from untreated MSW. Aerobic pretreatment of MSW prior to landfilling reduces the organic content of the waste and the intensity of the NMOC emissions, and increases the odor threshold, thereby reducing the environmental impact of landfills. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Solvent-Controlled Chemoselectivity in the Photolytic Release of Hydroxamic Acids and Carboxamides from Solid Support

    DEFF Research Database (Denmark)

    Qvortrup, Katrine; Petersen, Rico G; Dohn, Asmus Ougaard

    2017-01-01

    The synthetic utility and theoretical basis of a photolabile hydroxylamine-linker are presented. The developed protocols enable the efficient synthesis and chemoselective photolytic release of either hydroxamates or carboxamides from solid support. The bidetachable mode of the linker unit...

  12. Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride.

    NARCIS (Netherlands)

    Plöger, Gerlinde F; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D I R K W; Langguth, Peter; Mehta, Mehul U; Parr, Alan; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Dressman, Jennifer B

    2018-01-01

    Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To clarify the Biopharmaceutics Classification System (BCS) classification, experimental solubility and

  13. Pharmacological aspects of release from microcapsules - from polymeric multilayers to lipid membranes.

    Science.gov (United States)

    Wuytens, Pieter; Parakhonskiy, Bogdan; Yashchenok, Alexey; Winterhalter, Mathias; Skirtach, Andre

    2014-10-01

    This review is devoted to pharmacological applications of principles of release from capsules to overcome the membrane barrier. Many of these principles were developed in the context of polymeric multilayer capsule membrane modulation, but they are also pertinent to liposomes, polymersomes, capsosomes, particles, emulsion-based carriers and other carriers. We look at these methods from the physical, chemical or biological driving mechanisms point of view. In addition to applicability for carriers in drug delivery, these release methods are significant for another area directly related to pharmacology - modulation of the permeability of the membranes and thus promoting the action of drugs. Emerging technologies, including ionic current monitoring through a lipid membrane on a nanopore, are also highlighted. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Preparation, characterization, and optimization of primaquine-loaded solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Omwoyo WN

    2014-08-01

    Full Text Available Wesley Nyaigoti Omwoyo,1,2 Bernhards Ogutu,3,4 Florence Oloo,3,5 Hulda Swai,6 Lonji Kalombo,6 Paula Melariri,6 Geoffrey Maroa Mahanga,2 Jeremiah Waweru Gathirwa3,4 1Department of Chemistry, Maasai Mara University, Narok, Kenya; 2Department of Chemistry, Jaramogi Oginga Odinga University of Science and Technology, Bondo, Kenya; 3Center for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya; 4Kenya Medical Research Institute, Nairobi, Kenya; 5Department of Chemical Sciences and Technology, Technical University of Kenya, Nairobi, Kenya; 6Department of Polymers and Composites, Council for Scientific and Industrial Research, Pretoria, South Africa Abstract: Primaquine (PQ is one of the most widely used antimalarial drugs and is the only available drug that combats the relapsing form of malaria. PQ use in higher doses is limited by severe tissue toxicity including hematological- and gastrointestinal-related side effects. Nanoformulation of drugs in an appropriate drug carrier system has been extensively studied and shown to have the potential to improve bioavailability, thereby enhancing activity, reducing dose frequency, and subsequently reducing toxicity. The aim of this work was to design, synthesize, and characterize PQ-loaded solid lipid nanoparticles (SLNs (PQ-SLNs as a potential drug-delivery system. SLNs were prepared by a modified solvent emulsification evaporation method based on a water-in-oil-in-water (w/o/w double emulsion. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the PQ-SLNs were 236 nm, +23 mV, 14%, and 75%, respectively. The zeta potential of the SLNs changed dramatically, from -6.54 mV to +23.0 mV, by binding positively charged chitosan as surface modifier. A spherical morphology of PQ-SLNs was seen by scanning electron microscope. In vitro, release profile depicted a steady drug release over 72 hours. Differential scanning calorimeter thermograms demonstrated presence

  15. Solid lipid nanoparticle suspension enhanced the therapeutic efficacy of praziquantel against tapeworm

    Directory of Open Access Journals (Sweden)

    Xie S

    2011-10-01

    Full Text Available Shuyu Xie1,*, Baoliang Pan1,*, Baoxin Shi2, Zhuangzhi Zhang2, Xu Zhang2, Ming Wang1, Wenzhong Zhou11Department of Preventive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China; 2Veterinary Research Institute, Xinjiang Academy of Animal Science, Xinjiang, People’s Republic of China *These authors contributed equally to this study Abstract: Hydatid disease caused by tapeworm is an increasing public health and socioeconomic concern. In order to enhance the therapeutic efficacy of praziquantel (PZQ against tapeworm, PZQ-loaded hydrogenated castor oil solid lipid nanoparticle (PZQ-HCO-SLN suspension was prepared by a hot homogenization and ultrasonication method. The stability of the suspension at 4°C and room temperature was evaluated by the physicochemical characteristics of the nanoparticles and in-vitro release pattern of the suspension. Pharmacokinetics was studied after subcutaneous administration of the suspension in dogs. The therapeutic effect of the novel formulation was evaluated in dogs naturally infected with Echinococcus granulosus. The results showed that the drug recovery of the suspension was 97.59% ± 7.56%. Nanoparticle diameter, polydispersivity index, and zeta potential were 263.00 ± 11.15 nm, 0.34 ± 0.06, and -11.57 ± 1.12 mV, respectively and showed no significant changes after 4 months of storage at both 4°C and room temperature. The stored suspensions displayed similar in-vitro release patterns as that of the newly prepared one. SLNs increased the bioavailability of PZQ 5.67-fold and extended the mean residence time of the drug from 56.71 to 280.38 hours. Single subcutaneous administration of PZQ-HCO-SLN suspension obtained enhanced therapeutic efficacy against tapeworm in infected dogs. At the dose of 5 mg/kg, the stool-ova reduction and negative conversion rates and tapeworm removal rate of the suspension were 100%, while the native PZQ were 91

  16. Characterization and evaluation of 5-fluorouracil-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification technique.

    Science.gov (United States)

    Patel, Meghavi N; Lakkadwala, Sushant; Majrad, Mohamed S; Injeti, Elisha R; Gollmer, Steven M; Shah, Zahoor A; Boddu, Sai Hanuman Sagar; Nesamony, Jerry

    2014-12-01

    The aim of this research was to advance solid lipid nanoparticle (SLN) preparation methodology by preparing glyceryl monostearate (GMS) nanoparticles using a temperature-modulated solidification process. The technique was reproducible and prepared nanoparticles without the need of organic solvents. An anticancer agent, 5-fluorouracil (5-FU), was incorporated in the SLNs. The SLNs were characterized by particle size analysis, zeta potential analysis, differential scanning calorimetry (DSC), infrared spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), drug encapsulation efficiency, in vitro drug release, and in vitro cell viability studies. Particle size of the SLN dispersion was below 100 nm, and that of redispersed lyophilizates was ~500 nm. DSC and infrared spectroscopy suggested that the degree of crystallinity did not decrease appreciably when compared to GMS. TEM and AFM images showed well-defined spherical to oval particles. The drug encapsulation efficiency was found to be approximately 46%. In vitro drug release studies showed that 80% of the encapsulated drug was released within 1 h. In vitro cell cultures were biocompatible with blank SLNs but demonstrated concentration-dependent changes in cell viability to 5-FU-loaded SLNs. The 5-FU-loaded SLNs can potentially be utilized in an anticancer drug delivery system.

  17. Novel bio-active lipid nanocarriers for the stabilization and sustained release of sitosterol

    International Nuclear Information System (INIS)

    Lacatusu, I; Badea, N; Stan, R; Meghea, A

    2012-01-01

    In this work, new stable and efficiently bio-active lipid nanocarriers (NLCs) with antioxidant properties have been developed for the transport of active ingredients in food. The novel NLCs loaded with β-sitosterol/β-sitosterol and green tea extract (GTE) and prepared by a combination of natural oils (grape seed oil, fish oil and squalene) and biological lipids with food grade surfactants, were physico-chemically examined by DLS, TEM, electrokinetic potential, DSC and HPLC and found to have main diameters less than 200 nm, a spherical morphology, excellent physical stability, an imperfect crystalline lattice and high entrapment efficiency. The novel loaded-NLCs have demonstrated the potential to develop a high blocking action of chain reactions, trapping up to 92% of the free-oxygen radicals, as compared to the native β-sitosterol (AA%=36.5). Another advantage of this study is associated with the quality of bio-active NLCs based on grape seed oil and squalene to manifest a better sitosterol—sustained release behaviour as compared to their related nanoemulsions. By coupling both in vitro results, i.e. the enhanced antioxidant activity and superior release properties, this study emphasizes the sustainability of novel bio-active nanocarriers to gain specific bio-food features for development of functional foods with a high applicability spectrum. (paper)

  18. Formulation of Fast-Release Gastroretentive Solid Dispersion of ...

    African Journals Online (AJOL)

    Methods: Hot melt granulation technique was adopted to prepare solid dispersions (SDs) of glibenclamide in .... ml of 0.1M HCl (pH 1.2), stirred at 20 rpm in a water bath (25 ± 0.3 .... cm-1; and SO2 stretching vibration at 1340.43 and 1159.14 ...

  19. Development of free-flowing peppermint essential oil-loaded hollow solid lipid micro- and nanoparticles via atomization with carbon dioxide.

    Science.gov (United States)

    Yang, Junsi; Ciftci, Ozan Nazim

    2016-09-01

    The main objective of this study was to overcome the issues related to the volatility and strong smell that limit the efficient utilization of essential oils as "natural" antimicrobials in the food industry. Peppermint essential oil-loaded hollow solid lipid micro- and nanoparticles were successfully formed using a novel "green" method based on atomization of CO 2 -expanded lipid mixture. The highest essential oil loading efficiency (47.5%) was achieved at 50% initial essential oil concentration at 200bar expansion pressure and 50μm nozzle diameter, whereas there was no significant difference between the loading efficiencies (35%-39%) at 5%, 7%, 10%, and 20% initial essential oil concentrations (p>0.05). Particles generated at all initial essential oil concentrations were spherical but increasing the initial essential oil concentration to 20% and 50% generated a less smooth particle surface. After 4weeks of storage, 61.2%, 42.5%, 0.2%, and 2.0% of the loaded essential oil was released from the particles formed at 5%, 10%, 20%, and 50% initial essential oil concentrations, respectively. This innovative simple and clean process is able to form spherical hollow micro- and nanoparticles loaded with essential oil that can be used as food grade antimicrobials. These novel hollow solid lipid micro- and nanoparticles are alternatives to the solid lipid nanoparticles, and overcome the issues associated with the solid lipid nanoparticles. The dry free-flowing products make the handling and storage more convenient, and the simple and clean process makes the scaling up more feasible. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Solid Lipid Nanoparticle Formulations of Docetaxel Prepared with High Melting Point Triglycerides: In Vitro and in Vivo Evaluation

    Science.gov (United States)

    2015-01-01

    Docetaxel (DCX) is a second generation taxane. It is approved by the U.S. Food and Drug Administration for the treatment of various types of cancer, including breast, non-small cell lung, and head and neck cancers. However, side effects, including those related to Tween 80, an excipient in current DCX formulations, can be severe. In the present study, we developed a novel solid lipid nanoparticle (SLN) composition of DCX. Trimyristin was selected from a list of high melting point triglycerides as the core lipid component of the SLNs, based on the rate at which the DCX was released from the SLNs and the stability of the SLNs. The trimyristin-based, PEGylated DCX-incorporated SLNs (DCX-SLNs) showed significantly higher cytotoxicity against various human and murine cancer cells in culture, as compared to DCX solubilized in a Tween 80/ethanol solution. Moreover, in a mouse model with pre-established tumors, the new DCX-SLNs were significantly more effective than DCX solubilized in a Tween 80/ethanol solution in inhibiting tumor growth without toxicity, likely because the DCX-SLNs increased the concentration of DCX in tumor tissues, but decreased the levels of DCX in major organs such as liver, spleen, heart, lung, and kidney. DCX-incorporated SLNs prepared with one or more high-melting point triglycerides may represent an improved DCX formulation. PMID:24621456

  1. Application of Response Surface Methodology for the Technological Improvement of Solid Lipid Nanoparticles.

    Science.gov (United States)

    Dal Pizzol, Carine; O'Reilly, Andre; Winter, Evelyn; Sonaglio, Diva; de Campos, Angela Machado; Creczynski-Pasa, Tânia Beatriz

    2016-02-01

    Solid lipid nanoparticles (SLN) are colloidal particles consisting of a matrix composed of solid (at room and body temperatures) lipids dispersed in aqueous emulsifier solution. During manufacture, their physicochemical properties may be affected by several formulation parameters, such as type and concentration of lipid, proportion of emulsifiers and amount of solvent. Thus, the aim of this work was to study the influence of these variables on the preparation of SLN. A D-optimal Response Surface Methodology design was used to establish a mathematical model for the optimization of SLN. A total of 30 SLN formulations were prepared using the ultrasound method, and then characterized on the basis of their physicochemical properties, including particle size, polydispersity index (PI) and Zeta Potential (s). Particle sizes ranged between 107 and 240 nm. All SLN formulations showed negative sigma and PI values below 0.28. Prediction of the optimal conditions was performed using the desirability function targeting the reduction of all responses. The optimized SLN formulation showed similar theoretical and experimental values, confirming the sturdiness and predictive ability of the mathematical model for SLN optimization.

  2. Loading of praziquantel in the crystal lattice of solid lipid nanoparticles - studies by DSC and SAXS

    Energy Technology Data Exchange (ETDEWEB)

    Souza, A.L.R.; Cassimiro, D.L.; Almeida, A.E.; Ribeiro, C.A.; Gremiao, M.P.D. [UNESP, Araraquara, SP (Brazil); Sarmento, V.H.V. [Universidade Federal de Sergipe (UFS), Itabaiana, SE (Brazil); Andreani, T.; Silva, A.M.; Souto, E.B. [Universidade de Tras-os-Montes e Alto Douro, Vila Real (Portugal)

    2012-07-01

    Full text: Praziquantel (PZQ) is the drug of choice for oral treatment of schistosomiasis and other fluke infections that affect humans. Its low oral bioavailability demands the development of innovative strategies to overcome the first pass metabolism. In this work, solid lipid nanoparticles loaded with PZQ (PZQ-SLN) were prepared by a modified oil-in-water microemulsion method selecting stearic acid as lipid phase after solubility screening studies. The mean particle size (Z-Ave) and zeta potential (ZP) were 500 nm and -34.0 mV, respectively. Morphology and shape of PZQ-SLN were analysed by scanning electron microscopy revealing the presence of spherical particles with smooth surface. Differential scanning calorimetry suggested that SLN comprised a less ordered arrangement of crystals and the drug was molecularly dispersed in the lipid matrix. No supercooled melts were detected. The entrapment efficiency (EE) and loading capacity of PZQ, determined by high performance liquid chromatography, were 99.0 and 17.5, respectively. Effective incorporation of PZQ into the particles was confirmed by small angle X-ray scattering revealing the presence of a lipid lamellar structure. Stability parameters of PZQ-SLN stored at room temperature (25 deg C) and at 4 deg C were checked by analysing Z-Ave, ZP and the EE for a period of 60 days Results showed a relatively long-term physical stability after storage at 4 deg C, without drug expulsion. (author)

  3. Loading of praziquantel in the crystal lattice of solid lipid nanoparticles - studies by DSC and SAXS

    International Nuclear Information System (INIS)

    Souza, A.L.R.; Cassimiro, D.L.; Almeida, A.E.; Ribeiro, C.A.; Gremiao, M.P.D.; Sarmento, V.H.V.; Andreani, T.; Silva, A.M.; Souto, E.B.

    2012-01-01

    Full text: Praziquantel (PZQ) is the drug of choice for oral treatment of schistosomiasis and other fluke infections that affect humans. Its low oral bioavailability demands the development of innovative strategies to overcome the first pass metabolism. In this work, solid lipid nanoparticles loaded with PZQ (PZQ-SLN) were prepared by a modified oil-in-water microemulsion method selecting stearic acid as lipid phase after solubility screening studies. The mean particle size (Z-Ave) and zeta potential (ZP) were 500 nm and -34.0 mV, respectively. Morphology and shape of PZQ-SLN were analysed by scanning electron microscopy revealing the presence of spherical particles with smooth surface. Differential scanning calorimetry suggested that SLN comprised a less ordered arrangement of crystals and the drug was molecularly dispersed in the lipid matrix. No supercooled melts were detected. The entrapment efficiency (EE) and loading capacity of PZQ, determined by high performance liquid chromatography, were 99.0 and 17.5, respectively. Effective incorporation of PZQ into the particles was confirmed by small angle X-ray scattering revealing the presence of a lipid lamellar structure. Stability parameters of PZQ-SLN stored at room temperature (25 deg C) and at 4 deg C were checked by analysing Z-Ave, ZP and the EE for a period of 60 days Results showed a relatively long-term physical stability after storage at 4 deg C, without drug expulsion. (author)

  4. Cationic solid lipid nanoparticles enhance ocular hypotensive effect of melatonin in rabbit.

    Science.gov (United States)

    Leonardi, Antonio; Bucolo, Claudio; Drago, Filippo; Salomone, Salvatore; Pignatello, Rosario

    2015-01-15

    The study was aimed at evaluating whether the ocular hypotensive effect of melatonin (MEL) was enhanced by its encapsulation in cationic solid lipid nanoparticles (cSLN), as well as at determining the tolerability of these formulations on the ocular surface. MEL was loaded in cSLN that had already been shown to be suitable for ophthalmic use. The formulations were prepared using Softisan(®) 100 as the main lipid matrix, with the presence of either stearic (SA) or palmitic acid (PA) as lipid modifiers. A fixed positive charge was provided by the addition of a cationic lipid (didecyldimethylammonium bromide). The ocular hypotensive effect was evaluated by measuring the intraocular pressure (IOP) during 24h in albino rabbits. MEL elicited a significant (p<0.01) IOP reduction in rabbit eye. All the formulations tested in vivo demonstrated a good tolerability. The nanocarrier containing SA was the most effective in terms of IOP reduction (maximum IOP reduction: -7 mmHg), and its effect lasted approximately 24h. The experimental data indicate that the new formulations based on cSLN loaded with MEL represent a potent anti-glaucoma treatment with a safe profile, warranting further clinical evaluation of the proposed nanotechnological strategy. Copyright © 2014. Published by Elsevier B.V.

  5. Increased therapeutic efficacy of a newly synthesized tyrosinase inhibitor by solid lipid nanoparticles in the topical treatment of hyperpigmentation

    Directory of Open Access Journals (Sweden)

    Al-Amin M

    2016-12-01

    Full Text Available Md Al-Amin, Jiafu Cao, Muhammad Naeem, Hasanul Banna, Min-Soo Kim, Yunjin Jung, Hae Young Chung, Hyung Ryong Moon, Jin-Wook Yoo College of Pharmacy, Pusan National University, Busan, South Korea Abstract: Hyperpigmentation caused by melanin overproduction is a major skin disorder in humans. Inhibition of tyrosinase, a key regulator of melanin production, has been used as an effective strategy to treat hyperpigmentation. In this study, we investigated the use of solid lipid nanoparticles (SLNs as a highly effective and nontoxic means to deliver a newly synthesized potent tyrosinase inhibitor, MHY498, and to target melanocytes through the skin. MHY498-loaded SLNs (MHY-SLNs were prepared by an oil-in-water emulsion solvent-evaporation method, and their morphological and physicochemical properties were characterized. MHY-SLNs showed a prolonged drug-release profile and higher skin permeation than that of MHY solution. In an in vivo evaluation of antimelanogenic activity, MHY-SLNs showed a prominent inhibitory effect against ultraviolet B-induced melanogenesis, resulting in no change in the skin color of C57BL/6 mouse, compared with that observed in an MHY solution-treated group and an untreated control group. The antimelanogenic effect of MHY-SLNs was further confirmed through Fontana–Masson staining. Importantly, MHY-SLNs did not induce any toxic effects in the L929 cell line. Overall, these data indicate that MHY-SLNs show promise in the topical treatment of hyperpigmentation. Keywords: melanogenesis, hyperpigmentation, MHY498, solid lipid nanoparticles, skin delivery

  6. 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

  7. PEGylated lipid nanocapsules with improved drug encapsulation and controlled release properties.

    Science.gov (United States)

    Hervella, Pablo; Alonso-Sande, Maria; Ledo, Francisco; Lucero, Maria L; Alonso, Maria J; Garcia-Fuentes, Marcos

    2014-01-01

    Drugs with poor lipid and water solubility are some of the most challenging to formulate in nanocarriers, typically resulting in low encapsulation efficiencies and uncontrolled release profiles. PEGylated nanocapsules (PEG-NC) are known for their amenability to diverse modifications that allow the formation of domains with different physicochemical properties, an interesting feature to address a drug encapsulation problem. We explored this problem by encapsulating in PEG-NC the promising anticancer drug candidate F10320GD1, used herein as a model for compounds with such characteristics. The nanocarriers were prepared from Miglyol(®), lecithin and PEG-sterate through a solvent displacement technique. The resulting system was a homogeneous suspension of particles with size around 200 nm. F10320GD1 encapsulation was found to be very poor (<15%) if PEG-NC were prepared using water as continuous phase; but we were able to improve this value to 85% by fixing the pH of the continuous phase to 9. Interestingly, this modification also improved the controlled release properties and the chemical stability of the formulation during storage. These differences in pharmaceutical properties together with physicochemical data suggest that the pH of the continuous phase used for PEG-NC preparation can modify drug allocation, from the external shell towards the inner lipid core of the nanocapsules. Finally, we tested the bioactivity of the drug-loaded PEG-NC in several tumor cell lines, and also in endothelial cells. The results indicated that drug encapsulation led to an improvement on drug cytotoxicity in tumor cells, but not in non-tumor endothelial cells. Altogether, the data confirms that PEG-NC show adequate delivery properties for F10320GD1, and underlines its possible utility as an anticancer therapy.

  8. Preparation of oridonin-loaded solid lipid nanoparticles and studies on them in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Dianrui [College of Life Science and Technology, Beijing University of Chemical Technology, 15 Bei Sanhuan Donglu, Beijing 100029 (China); Tan Tianwei [College of Life Science and Technology, Beijing University of Chemical Technology, 15 Bei Sanhuan Donglu, Beijing 100029 (China); Gao Lei [Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012 (China)

    2006-12-14

    Oridonin, a lipophilic Chinese medicine, has very low oral bioavailability due to its poor solubility. Solid lipid nanoparticle (SLN) delivery systems of oridonin have been formed using stearic acid, soybean lecithin and pluronic F{sub 68} in our studies to overcome this problem. Emulsion evaporation-solidification at low temperature was used to prepare SLN dispersions. The particle size and morphology were examined by transmission electron microscopy (TEM), and the zeta potential was measured by a television micro-electrophoresis apparatus. Process and formulation variables have been studied and optimized on the basis of entrapment efficiency. Differential scanning calorimetry (DSC) and powder x-ray diffraction (PXRD) studies were performed to characterize the state of the drug. In vitro release studies were performed in phosphate-buffer solution (PBS) (pH 7.4). The tissue distribution in mice and the pharmacokinetics in rabbits were studied to evaluate the tissue targeted property of SLNs. Stable SLN formulations of oridonin having a mean size range of 15-35 nm and mean zeta potential -45.07 mV were developed. More than 40% oridonin was entrapped in SLNs. DSC and PXRD analysis showed that oridonin is dispersed in SLNs in an amorphous state. The release pattern of the drug was analysed and found to follow the Higuchi equations. In vivo studies demonstrated that oridonin-loaded SLNs obviously increased the concentration of oridonin in liver, lung and spleen, while its distribution in heart and kidney decreased.

  9. Development of terbinafine solid lipid nanoparticles as a topical delivery system

    Science.gov (United States)

    Chen, Ying-Chen; Liu, Der-Zen; Liu, Jun-Jen; Chang, Tsung-Wei; Ho, Hsiu-O; Sheu, Ming-Thau

    2012-01-01

    To resolve problems of long treatment durations and frequent administration of the antifungal agent terbinafine (TB), solid lipid nanoparticles (SLNs) with the ability to load lipophilic drugs and nanosize were developed. The SLNs were manufactured by a microemulsion technique in which glyceryl monostearate (GMS), glyceryl behenate (Compritol® 888; Gattefossé), and glyceryl palmitostearate (Precirol® ATO 5; Gattefossé) were used as the solid lipid phases, Tween® and Cremophor® series as the surfactants, and propylene glycol as the cosurfactant to construct ternary phase diagrams. The skin of nude mice was used as a barrier membrane, and penetration levels of TB of the designed formulations and a commercial product, Lamisil® Once™ (Novartis Pharmaceuticals), in the stratum corneum (SC), viable epidermis, and dermis were measured; particle sizes were determined as an indicator of stability. The optimal SLN system contained a 50% water phase. The addition of ethanol or etchants had no significant effect on enhancing the amount of TB that penetrated the skin layers, but it was enhanced by increasing the percentage of the lipid phase. Furthermore, the combination of GMS and Compritol® 888 was able to increase the stable amount of TB that penetrated all skin layers. For the ACP1-GM1 (4% lipid phase; Compritol® 888: GMS of 1:1) formulation, the amount of TB that penetrated the SC was similar to that of Lamisil® Once™, whereas the amount of TB of the dermis was higher than that of Lamisil® Once™ at 12 hours, and it was almost the same as that of Lamisil® Once™ at 24 hours. It was concluded that the application of ACP1-GM1 for 12 hours might have an efficacy comparable to that of Lamisil® Once™ for 24 hours, which would resolve the practical problem of the longer administration period that is necessary for Lamisil® Once™. PMID:22923986

  10. Mesophilic co-digestion of dairy manure and lipid rich solid slaughterhouse wastes: process efficiency, limitations and floating granules formation.

    Science.gov (United States)

    Pitk, Peep; Palatsi, Jordi; Kaparaju, Prasad; Fernández, Belén; Vilu, Raivo

    2014-08-01

    Lipid and protein rich solid slaughterhouse wastes are attractive co-substrates to increase volumetric biogas production in co-digestion with dairy manure. Addition of decanter sludge (DS), containing 42.2% of lipids and 35.8% of proteins (total solids basis), up to 5% of feed mixture resulted in a stable process without any indication of long chain fatty acids (LCFA) or free ammonia (NH3) inhibition and in 3.5-fold increase of volumetric biogas production. Contrary, only lipids addition as technical fat (TF) at over 2% of feed mixture resulted in formation of floating granules (FG) and process efficiency decrease. Formed FG had low biodegradability and its organic part was composed of lipids and calcium salts of LCFAs. Anaerobic digestion process intentionally directed to FG formation, could be a viable option for mitigation and control of lipids overload and derived LCFA inhibition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Solid Lipid Nanoparticles as Efficient Drug and Gene Delivery Systems: Recent Breakthroughs

    Directory of Open Access Journals (Sweden)

    Jafar Ezzati Nazhad Dolatabadi

    2015-06-01

    Full Text Available In recent years, nanomaterials have been widely applied as advanced drug and gene delivery nanosystems. Among them, solid lipid nanoparticles (SLNs have attracted great attention as colloidal drug delivery systems for incorporating hydrophilic or lipophilic drugs and various macromolecules as well as proteins and nucleic acids. Therefore, SLNs offer great promise for controlled and site specific drug and gene delivery. This article includes general information about SLN structures and properties, production procedures, characterization. In addition, recent progress on development of drug and gene delivery systems using SLNs was reviewed.

  12. In-vitro release of diclofenac diethylammonium from lipid-based formulations.

    Science.gov (United States)

    Parsaee, Siamak; Sarbolouki, Mohammad N; Parnianpour, Mohamad

    2002-07-08

    This article presents the preparation and topical performance of some new lipid-based formulations of diclofenac, namely (a) a diclofenac aqueous gel containing mixed micelles (sodium cholate:egg lecithin molar ratio 0.55); (b) diclofenac lotion that contains soya lecithin, ethanol and buffer; and (c) diclofenac lipogel containing egg lecithin, isopropyl myristate, propylene glycol and ethanol. Gel formulations were prepared using Carbomer 934. Release of diclofenac from all formulations was monitored via dialysis through Spectra/por membrane into phosphate buffer (0.2 M pH=7.4) using a Franz cell. Drug release profile and diffusion coefficients were compared with brand formulation (Geigy's Vlotaren Emulgel). Statistical analysis of data show that the diffusion coefficient of the drug from these formulations rank according to the following order: Diclofenac lotion (D=5.308x10(-7) cm(2)/s) >lipogel (D=2.102 x 10(-7) cm(2)/s) >Voltaren Emulgel (1.518 x 10(-7) cm(2)/s) >aqueous gel mixed micelle (0.966 x 10(-7) cm(2)/s). These results show that diclofenac lotion and lipogel maybe more suitable formulations than the conventional topical dosage form.

  13. Artificial Neural Networks in Evaluation and Optimization of Modified Release Solid Dosage Forms

    Directory of Open Access Journals (Sweden)

    Zorica Djurić

    2012-10-01

    Full Text Available Implementation of the Quality by Design (QbD approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms.

  14. An investigation into the use of lipid matrices for the controlled release of therapeutic agents

    International Nuclear Information System (INIS)

    Khan, Nurzalina Abdul Karim

    2001-01-01

    Gelucires are pharmaceutical excipients made from hydrogenated vegetable oils and polyglycolised fatty acids. The variety of components within the gelucire can result in complex carrier characteristics ranging from the polymorphic changes of the lipid components to the interaction of the incorporated drugs with one or more carrier components. The effects of adding two different model drugs on the structure of Gelucire 50/13 and the influence of the drug loading were established. Thermal analysis techniques such as Hot-Stage Microscopy (HSM) and Differential Scanning Calorimetry (DSC) were utilised for morphological and structural studies. These techniques showed that the addition of paracetamol caused a marked change to the DSC thermal profile by stabilising the lowest melting form of the gelucire whereas caffeine did not significantly affect it. Dissolution studies were performed and the mechanisms of release were determined from the fitting of mathematical models to the release data. Additionally, results from erosion and water uptake studies performed by physically measuring the extent of each process on the matrices were found to be related to those obtained by mathematical fitting. A difference in the contributions of erosion and diffusion to drug release arose due to the different drugs added. The loadings of drug did not greatly affect the parameters studied. The effects of ageing the matrices at two different temperatures and at various time intervals were also investigated. In addition to the techniques above, Scanning Electron Microscopy (SEM) was also performed and it was found that the addition of a sterically compatible emulsifier such as sorbitan monostearate inhibited the blooming of stable crystals on the surfaces of the matrices. It was also found that storage at a higher temperature tempered the matrices to a more stable form and the extent of the ageing effect was also influenced by the drug incorporated. (author)

  15. An investigation into the use of lipid matrices for the controlled release of therapeutic agents

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Nurzalina Abdul Karim

    2001-07-01

    Gelucires are pharmaceutical excipients made from hydrogenated vegetable oils and polyglycolised fatty acids. The variety of components within the gelucire can result in complex carrier characteristics ranging from the polymorphic changes of the lipid components to the interaction of the incorporated drugs with one or more carrier components. The effects of adding two different model drugs on the structure of Gelucire 50/13 and the influence of the drug loading were established. Thermal analysis techniques such as Hot-Stage Microscopy (HSM) and Differential Scanning Calorimetry (DSC) were utilised for morphological and structural studies. These techniques showed that the addition of paracetamol caused a marked change to the DSC thermal profile by stabilising the lowest melting form of the gelucire whereas caffeine did not significantly affect it. Dissolution studies were performed and the mechanisms of release were determined from the fitting of mathematical models to the release data. Additionally, results from erosion and water uptake studies performed by physically measuring the extent of each process on the matrices were found to be related to those obtained by mathematical fitting. A difference in the contributions of erosion and diffusion to drug release arose due to the different drugs added. The loadings of drug did not greatly affect the parameters studied. The effects of ageing the matrices at two different temperatures and at various time intervals were also investigated. In addition to the techniques above, Scanning Electron Microscopy (SEM) was also performed and it was found that the addition of a sterically compatible emulsifier such as sorbitan monostearate inhibited the blooming of stable crystals on the surfaces of the matrices. It was also found that storage at a higher temperature tempered the matrices to a more stable form and the extent of the ageing effect was also influenced by the drug incorporated. (author)

  16. Evaluation of hypericin-loaded solid lipid nanoparticles: physicochemical properties, photostability and phototoxicity.

    Science.gov (United States)

    Youssef, Tareq; Fadel, Maha; Fahmy, Rania; Kassab, Kawser

    2012-01-01

    Hypericin (HYP), a natural photosensitizer, has powerful photo-oxidizing ability, tumor-seeking characteristics, and minimal dark toxicity; nevertheless, it has proven high lipid solubility compared to its sparingly water soluble nature. Therefore, its formulation into solid lipid nanoparticles (SLNs) has attracted increasing attention as a potential drug-delivery carrier. Two HYP-loaded SLNs formulations were prepared utilizing microemulsion-based technique. Thereafter, the physicochemical properties of the formulations were investigated and evaluated. HYP-loaded SLNs showed spherical shape with mean particle size ranging from 200-300 nm for both formulations (FA and FB). The encapsulation efficiencies reached above 80% and FA showed significant higher encapsulation than FB (Phypericin and lipids forming the cores in both formulations. Spectroscopic measurements of the photostability study showed that hypericin encapsulation into SLNs improved its photostability, compared to free HYP in 0.1% ethanolic solution. However, photocytotoxicity studies on HepG2 cells revealed an evident inhibition of the photodynamic efficacy of HYP-loaded SLNs, compared to free HYP. In conclusion, although the elevated entrapment efficiency of HYP into SLNs increased its photostability, it decreased its phototoxicity which might be due to the quenching deactivation of HYP molecules resulting from SLN compactness and thickness structure. © 2012 Informa Healthcare USA, Inc.

  17. Physical-Chemical Characterization and Formulation Considerations for Solid Lipid Nanoparticles.

    Science.gov (United States)

    Chauhan, Harsh; Mohapatra, Sarat; Munt, Daniel J; Chandratre, Shantanu; Dash, Alekha

    2016-06-01

    Pure glyceryl mono-oleate (GMO) (lipid) and different batches of GMO commonly used for the preparation of GMO-chitosan nanoparticles were characterized by modulated differential scanning calorimetry (MDSC), cryo-microscopy, and cryo-X-ray powder diffraction techniques. GMO-chitosan nanoparticles containing poloxamer 407 as a stabilizer in the absence and presence of polymers as crystallization inhibitors were prepared by ultrasonication. The effect of polymers (polyvinyl pyrrolidone (PVP), Eudragits, hydroxyl propyl methyl cellulose (HPMC), polyethylene glycol (PEG)), surfactants (poloxamer), and oils (mineral oil and olive oil) on the crystallization of GMO was investigated. GMO showed an exothermic peak at around -10°C while cooling and another exothermic peak at around -12°C while heating. It was followed by two endothermic peaks between 15 and 30 C, indicative of GMO melting. The results are corroborated by cryo-microscopy and cryo-X-ray. Significant differences in exothermic and endothermic transition were observed between different grades of GMO and pure GMO. GMO-chitosan nanoparticles resulted in a significant increase in particle size after lyophilization. MDSC confirmed that nanoparticles showed similar exothermic crystallization behavior of lipid GMO. MDSC experiments showed that PVP inhibits GMO crystallization and addition of PVP showed no significant increase in particle size of solid lipid nanoparticle (SLN) during lyophilization. The research highlights the importance of extensive physical-chemical characterization for successful formulation of SLN.

  18. Encapsulation of fish oil into hollow solid lipid micro- and nanoparticles using carbon dioxide.

    Science.gov (United States)

    Yang, Junsi; Ciftci, Ozan Nazim

    2017-09-15

    Fish oil was encapsulated in hollow solid lipid micro- and nanoparticles formed from fully hydrogenated soybean oil (FHSO) using a novel green method based on atomization of supercritical carbon dioxide (SC-CO 2 )-expanded lipid. The highest fish oil loading efficiency (97.5%, w/w) was achieved at 50%, w/w, initial fish oil concentration. All particles were spherical and in the dry free-flowing form; however, less smooth surface with wrinkles was observed when the initial fish oil concentration was increased up to 50%. With increasing initial fish oil concentration, melting point of the fish oil-loaded particles shifted to lower onset melting temperatures, and major polymorphic form transformed from α to β and/or β'. Oxidative stability of the loaded fish oil was significantly increased compared to the free fish oil (p<0.05). This innovative method forms free-flowing powder products that are easy-to-use solid fish oil formulation, which makes the handling and storage feasible and convenient. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Xue M

    2013-12-01

    Full Text Available Mei Xue, Ming-xing Yang, Wei Zhang, Xiu-min Li, De-hong Gao, Zhi-min Ou, Zhi-peng Li, Su-huan Liu, Xue-jun Li, Shu-yu Yang Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China Abstract: The high aqueous solubility, poor permeability, and absorption of berberine (BBR result in its low plasma level after oral administration, which greatly limits its clinical application. BBR solid lipid nanoparticles (SLNs were prepared to achieve improved bioavailability and prolonged effect. Developed SLNs showed homogeneous spherical shapes, small size (76.8 nm, zeta potential (7.87 mV, encapsulation efficiency (58%, and drug loading (4.2%. The power of X-ray diffraction combined with 1H nuclear magnetic resonance spectroscopy was employed to analyze chemical functional groups and the microstructure of BBR-SLNs, and indicated that the drug was wrapped in a lipid carrier. Single dose (50 mg/kg oral pharmacokinetic studies in rats showed significant improvement (P<0.05 in the peak plasma concentration, area under the curve, and variance of mean residence time of BBR-SLNs when compared to BBR alone (P<0.05, suggesting improved bioavailability. Furthermore, oral administration of both BBR and BBR-SLNs significantly suppressed body weight gain, fasting blood glucose levels, and homeostasis assessment of insulin resistance, and ameliorated impaired glucose tolerance and insulin tolerance in db/db diabetic mice. BBR-SLNs at high dose (100 mg/kg showed more potent effects when compared to an equivalent dose of BBR. Morphologic analysis demonstrated that BBR-SLNs potentially promoted islet function and protected the islet from regeneration. In conclusion, our study demonstrates that by entrapping BBR into SLNs the absorption of BBR and its anti-diabetic action were effectively enhanced. Keywords: berberine, solid lipid nanoparticles, pharmacokinetic, hypoglycemic effect

  20. The effect of a lipid composition and a surfactant on the characteristics of the solid lipid microspheres and nanospheres (SLM and SLN).

    Science.gov (United States)

    Sznitowska, Malgorzata; Wolska, Eliza; Baranska, Helena; Cal, Krzysztof; Pietkiewicz, Justyna

    2017-01-01

    Solid lipid microparticles (SLM) were produced by a two-step process that, firstly, involved the emulsification of the molten lipid phase in a heated aqueous phase and, secondly, the system cooling. Compritol 888 ATO and Precirol ATO 5, including their mixtures with Miglyol 812 or Witepsol H15 were used as lipid components (10-30% w/w). The average size of the SLM prepared with Compritol and Tween 80 as an emulsifier was 3-7μm and the influence of lipid concentration and thermal sterilization was not large. Dispersions of SLM with Precirol (10-20% w/w) gellified upon storage. SLM stabilized with another surfactant, Tego Care 450, were larger in size and measured 40μm on average. The use of the sonication step (5-15min) in hot formulations containing 5% w/w of Compritol resulted in the formation of the solid lipid nanoparticles (SLN) with average size 200-300nm. The smallest SLN size (below 100nm on average) was obtained in SLN that contained Tego Care and an antimicrobial agent Euxyl PE 9010; such combination evoked synergism between the surfactant and Euxyl components. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Lipids bearing extruded-spheronized pellets for extended release of poorly soluble antiemetic agent-Meclizine HCl.

    Science.gov (United States)

    Qazi, Faaiza; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Nasiri, Muhammad Iqbal; Ahmed, Kamran; Ahmad, Mansoor

    2017-04-12

    Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated. Thirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol ® ), Glyceryl palmitostearate (Precirol ® ), Glyceryl behenate (Compritol ® ) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found. Sphericity indicated by shape factor (e R ) varied with type and concentration of lipids: Geleol ® (e R  = 0.891-0.997), Precirol ® (e R  = 0.611-0.743), Compritol ® (e R  = 0.665-0.729) and Carnauba wax (e R  = 0.499-0.551). Highly spherical pellets were obtained with Geleol ® (Aspect ratio = 1.005-1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153-1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol ® and Compritol ® , (ii) Geleol ® and Carnauba wax and (iii) Geleol ® , Compritol ® and Carnauba wax. Scanning electron microscopy of Compritol ® pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol ® and Compritol ® pellets, explained by Korsmeyer-Peppas (R 2  = 0.978-0.993) indicated

  2. Floating solid cellulose nanofibre nanofoams for sustained release of the poorly soluble model drug furosemide

    DEFF Research Database (Denmark)

    Svagan, Anna Justina; Müllertz, Anette; Löbmann, Korbinian

    2017-01-01

    OBJECTIVES: This study aimed to prepare a furosemide-loaded sustained release cellulose nanofibre (CNF)-based nanofoams with buoyancy. METHODS: Dry foams consisting of CNF and the model drug furosemide at concentrations of 21% and 50% (w/w) have been prepared by simply foaming a CNF-drug suspension...... followed by drying. The resulting foams were characterized towards their morphology, solid state properties and dissolution kinetics. KEY FINDINGS: Solid state analysis of the resulting drug-loaded foams revealed that the drug was present as an amorphous sodium furosemide salt and in form of furosemide...... form I crystals embedded in the CNF foam cell walls. The foams could easily be shaped and were flexible, and during the drug release study, the foam pieces remained intact and were floating on the surface due to their positive buoyancy. Both foams showed a sustained furosemide release compared...

  3. A novel method to produce solid lipid nanoparticles using n-butanol as an additional co-surfactant according to the o/w microemulsion quenching technique.

    Science.gov (United States)

    Mojahedian, Mohammad M; Daneshamouz, Saeid; Samani, Soliman Mohammadi; Zargaran, Arman

    2013-09-01

    Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are novel medicinal carriers for controlled drug release and drug targeting in different roots of administration such as parenteral, oral, ophthalmic and topical. These carriers have some benefits such as increased drug stability, high drug payload, the incorporation of lipophilic and hydrophilic drugs, and no biotoxicity. Therefore, due to the cost-efficient, proportionally increasable, and reproducible preparation of SLN/NLC and the avoidance of organic solvents used, the warm microemulsion quenching method was selected from among several preparation methods for development in this research. To prepare the warm O/W microemulsion, lipids (distearin, stearic acid, beeswax, triolein alone or in combination with others) were melted at a temperature of 65°C. After that, different ratios of Tween60 (10-22.5%) and glyceryl monostearate (surfactant and co-surfactant) and water were added, and the combination was stirred. Then, 1-butanol (co-surfactant) was added dropwise until a clear microemulsion was formed and titration continued to achieve cloudiness (to obtain the microemulsion zone). The warm o/w microemulsions were added dropwise into 4°C water (1:5 volume ratio) while being stirred at 400 or 600 rpm. Lipid nanosuspensions were created upon the addition of the warm o/w microemulsion to the cold water. The SLN were obtained over a range of concentrations of co-surfactants and lipids and observed for microemulsion stability (clearness). For selected preparations, characterization involved also determination of mean particle size, polydispersity and shape. According to the aim of this study, the optimum formulations requiring the minimum amounts of 1-butanol (1.2%) and lower temperatures for creation were selected. Mono-disperse lipid nanoparticles were prepared in the size range 77 ± 1 nm to 124 ± 21 nm according to a laser diffraction particle size analyzer and transmission electron

  4. Microstructural effects in drug release by solid and cellular polymeric dosage forms: A comparative study.

    Science.gov (United States)

    Blaesi, Aron H; Saka, Nannaji

    2017-11-01

    In recent studies, we have introduced melt-processed polymeric cellular dosage forms to achieve both immediate drug release and predictable manufacture. Dosage forms ranging from minimally-porous solids to highly porous, open-cell and thin-walled structures were prepared, and the drug release characteristics investigated as the volume fraction of cells and the excipient molecular weight were varied. In the present study, both minimally-porous solid and cellular dosage forms consisting of various weight fractions of Acetaminophen drug and polyethylene glycol (PEG) excipient are prepared and analyzed. Microstructures of the solid forms and the cell walls range from single-phase solid solutions of the excipient and a small amount of drug molecules to two-phase composites of the excipient and tightly packed drug particles. Results of dissolution experiments show that the minimally-porous solid forms disintegrate and release drug by slow surface erosion. The erosion rate decreases as the drug weight fraction is increased. By contrast, the open-cell structures disintegrate rapidly by viscous exfoliation, and the disintegration time is independent of drug weight fraction. Drug release models suggest that the solid forms erode by convective mass transfer of the faster-eroding excipient if the drug volume fraction is small. At larger drug volume fractions, however, the slower-eroding drug particles hinder access of the free-flowing fluid to the excipient, thus slowing down erosion of the composite. Conversely, the disintegration rate of the cellular forms is limited by diffusion of the dissolution fluid into the excipient phase of the thin cell walls. Because the wall thickness is of the order of the drug particle size, and the particles are enveloped by the excipient during melt-processing, the drug particles cannot hinder diffusion through the excipient across the walls. Thus the disintegration time of the cellular forms is mostly unaffected by the volume fraction of drug

  5. Physico-chemical characterisation, cytotoxic activity, and biocompatibility studies of tamoxifen-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification method.

    Science.gov (United States)

    Lakkadwala, Sushant; Nguyen, Sanko; Lawrence, Joseph; Nauli, Surya M; Nesamony, Jerry

    2014-01-01

    Solid lipid nanoparticles (SLNs) can efficiently and efficaciously incorporate anti-cancer agents. To prepare and characterise tamoxifen (TAM)-loaded SLNs. Glyceryl monostearate, Tween-80, and trehalose were used in SLNs. SLNs were tested via dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Characterisation studies revealed SLNs of about 540 nm with a negative surface charge and confirmed the entrapment of TAM in the SLNs. The entrapment efficiency was estimated to be 60%. The in vitro drug release profile demonstrated a gradual increase followed by a release plateau for several days. A drug concentration-dependent increase in cytotoxic activity was observed when the SLNs were evaluated in cell cultures. Biocompatible and stable lyophilised SLNs were successfully prepared and found to possess properties that may be utilised in an anti-cancer drug delivery system.

  6. Transferrin-tailored solid lipid nanoparticles as vectors for site-specific delivery of temozolomide to brain

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Aviral, E-mail: draviraljain@gmail.com; Singhai, Priyanka; Gurnany, Ekta; Updhayay, Satish; Mody, Nishi [Adina Institute of Pharmaceutical Sciences, Pharmaceutics Research Laboratory, Department of Pharmaceutics (India)

    2013-03-15

    Blood-brain barrier restricts the uptake of many important hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms. In the present project, transferrin (Tf)-conjugated solid lipid nanoparticles (Tf-SLNs) were investigated for their ability to deliver temozolomide (TMZ) to the brain. SLNs were prepared by an ethanol injection method using hydrogenated soya phosphatidylcholine, triolein, cholesterol and distearoylphosphatidylethanolamine. Conjugation of SLNs with Tf was achieved by incubation of Tf with TMZ-loaded SLNs in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in phosphate buffered saline (pH 7.4) as a cross linker. SLNs preparation were characterized for particle size, polydispersity index, zeta potential, surface morphology, percent drug entrapment efficiency, in vitro drug release, and hemolytic toxicity studies. In vitro cytotoxicity studies were performed on human cancer cell lines. The average size was found to be 221 {+-} 3.22 nm with entrapment efficiency of 69.83 {+-} 2.52 and 249 {+-} 2.61 nm with entrapment efficiency decreased to 64.21 {+-} 2.27 % for unconjugated SLNs and Tf-SLNs, respectively. Fluorescence studies revealed the enhanced uptake of Tf-SLNs in brain tissue compared with unconjugated SLNs.

  7. Transferrin-tailored solid lipid nanoparticles as vectors for site-specific delivery of temozolomide to brain

    Science.gov (United States)

    Jain, Aviral; Singhai, Priyanka; Gurnany, Ekta; Updhayay, Satish; Mody, Nishi

    2013-03-01

    Blood-brain barrier restricts the uptake of many important hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms. In the present project, transferrin (Tf)-conjugated solid lipid nanoparticles (Tf-SLNs) were investigated for their ability to deliver temozolomide (TMZ) to the brain. SLNs were prepared by an ethanol injection method using hydrogenated soya phosphatidylcholine, triolein, cholesterol and distearoylphosphatidylethanolamine. Conjugation of SLNs with Tf was achieved by incubation of Tf with TMZ-loaded SLNs in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in phosphate buffered saline (pH 7.4) as a cross linker. SLNs preparation were characterized for particle size, polydispersity index, zeta potential, surface morphology, percent drug entrapment efficiency, in vitro drug release, and hemolytic toxicity studies. In vitro cytotoxicity studies were performed on human cancer cell lines. The average size was found to be 221 ± 3.22 nm with entrapment efficiency of 69.83 ± 2.52 and 249 ± 2.61 nm with entrapment efficiency decreased to 64.21 ± 2.27 % for unconjugated SLNs and Tf-SLNs, respectively. Fluorescence studies revealed the enhanced uptake of Tf-SLNs in brain tissue compared with unconjugated SLNs.

  8. Solid Lipid Nanoparticles Carrying Temozolomide for Melanoma Treatment. Preliminary In Vitro and In Vivo Studies

    Directory of Open Access Journals (Sweden)

    Nausicaa Clemente

    2018-01-01

    Full Text Available Aim: To develop an innovative delivery system for temozolomide (TMZ in solid lipid nanoparticles (SLN, which has been preliminarily investigated for the treatment of melanoma. Materials and Methods: SLN-TMZ was obtained through fatty acid coacervation. Its pharmacological effects were assessed and compared with free TMZ in in vitro and in vivo models of melanoma and glioblastoma. Results: Compared to the standard free TMZ, SLN-TMZ exerted larger effects, when cell proliferation of melanoma cells, and neoangiogeneis were evaluated. SLN-TMZ also inhibited growth and vascularization of B16-F10 melanoma in C57/BL6 mice, without apparent toxic effects. Conclusion: SLN could be a promising strategy for the delivery of TMZ, allowing an increased stability of the drug and thereby its employment in the treatment of aggressive malignacies.

  9. Solid Lipid Nanoparticles Carrying Temozolomide for Melanoma Treatment. Preliminary In Vitro and In Vivo Studies

    Science.gov (United States)

    Ferrara, Benedetta; Biasibetti, Elena; Schiffer, Davide; Mellai, Marta; Annovazzi, Laura; Cangemi, Luigi; Muntoni, Elisabetta; Dianzani, Umberto

    2018-01-01

    Aim: To develop an innovative delivery system for temozolomide (TMZ) in solid lipid nanoparticles (SLN), which has been preliminarily investigated for the treatment of melanoma. Materials and Methods: SLN-TMZ was obtained through fatty acid coacervation. Its pharmacological effects were assessed and compared with free TMZ in in vitro and in vivo models of melanoma and glioblastoma. Results: Compared to the standard free TMZ, SLN-TMZ exerted larger effects, when cell proliferation of melanoma cells, and neoangiogeneis were evaluated. SLN-TMZ also inhibited growth and vascularization of B16-F10 melanoma in C57/BL6 mice, without apparent toxic effects. Conclusion: SLN could be a promising strategy for the delivery of TMZ, allowing an increased stability of the drug and thereby its employment in the treatment of aggressive malignacies. PMID:29364157

  10. Investigating the correlation between in vivo absorption and in vitro release of fenofibrate from lipid matrix particles in biorelevant medium

    DEFF Research Database (Denmark)

    Borkar, Nrupa Nitin; Xia, Dengning; Holm, René

    2014-01-01

    Lipid matrix particles (LMP) may be used as better carriers for poorly water-soluble drugs than liquid lipid carriers because of reduced drug mobilization in the formulations. However, the digestion process of solid lipid particles and their effect on the absorption of poorly water-soluble drugs......-soluble drug, was incorporated into LMP in this study using probe ultrasound sonication. The resultant LMP were characterised in terms of particle size, size distribution, zeta potential, entrapment efficiency, in vitro lipolysis and in vivo absorption in rat model. LMP of three different particle sizes i.......e. approximately 100 nm, 400 nm, and 10 μm (microparticles) were produced with high entrapment efficiencies. The in vitro lipolysis study showed that the recovery of fenofibrate in the aqueous phase for 100 nm and 400 nm LMP was significantly higher (p

  11. Anti-Inflammatory Effects of Novel Standardized Solid Lipid Curcumin Formulations.

    Science.gov (United States)

    Nahar, Pragati P; Slitt, Angela L; Seeram, Navindra P

    2015-07-01

    Inflammation and the presence of pro-inflammatory cytokines are associated with numerous chronic diseases such as type-2 diabetes mellitus, cardiovascular disease, Alzheimer's disease, and cancer. An overwhelming amount of data indicates that curcumin, a polyphenol obtained from the Indian spice turmeric, Curcuma longa, is a potential chemopreventive agent for treating certain cancers and other chronic inflammatory diseases. However, the low bioavailability of curcumin, partly due to its low solubility and stability in the digestive tract, limits its therapeutic applications. Recent studies have demonstrated increased bioavailability and health-promoting effects of a novel solid lipid particle formulation of curcumin (Curcumin SLCP, Longvida(®)). The goal of this study was to evaluate the aqueous solubility and in vitro anti-inflammatory effects of solid lipid curcumin particle (SLCP) formulations using lipopolysaccharide (LPS)-stimulated RAW 264.7 cultured murine macrophages. SLCPs treatment significantly decreased nitric oxide (NO) and prostaglandin-E2 (PGE2) levels at concentrations ranging from 10 to 50 μg/mL, and reduced interleukin-6 (IL-6) levels in a concentration-dependent manner. Transient transfection experiments using a nuclear factor-kappa B (NF-κB) reporter construct indicate that SLCPs significantly inhibit the transcriptional activity of NF-κB in macrophages. Taken together, these results show that in RAW 264.7 murine macrophages, SLCPs have improved solubility over unformulated curcumin, and significantly decrease the LPS-induced pro-inflammatory mediators NO, PGE2, and IL-6 by inhibiting the activation of NF-κB.

  12. Statistical analysis of solid lipid nanoparticles produced by high-pressure homogenization: a practical prediction approach

    Energy Technology Data Exchange (ETDEWEB)

    Duran-Lobato, Matilde, E-mail: mduran@us.es [Universidad de Sevilla, Dpto. Farmacia y Tecnologia Farmaceutica, Facultad de Farmacia (Espana) (Spain); Enguix-Gonzalez, Alicia [Universidad de Sevilla, Dpto. Estadistica e Investigacion Operativa, Facultad de Matematicas (Espana) (Spain); Fernandez-Arevalo, Mercedes; Martin-Banderas, Lucia [Universidad de Sevilla, Dpto. Farmacia y Tecnologia Farmaceutica, Facultad de Farmacia (Espana) (Spain)

    2013-02-15

    Lipid nanoparticles (LNPs) are a promising carrier for all administration routes due to their safety, small size, and high loading of lipophilic compounds. Among the LNP production techniques, the easy scale-up, lack of organic solvents, and short production times of the high-pressure homogenization technique (HPH) make this method stand out. In this study, a statistical analysis was applied to the production of LNP by HPH. Spherical LNPs with mean size ranging from 65 nm to 11.623 {mu}m, negative zeta potential under -30 mV, and smooth surface were produced. Manageable equations based on commonly used parameters in the pharmaceutical field were obtained. The lipid to emulsifier ratio (R{sub L/S}) was proved to statistically explain the influence of oil phase and surfactant concentration on final nanoparticles size. Besides, the homogenization pressure was found to ultimately determine LNP size for a given R{sub L/S}, while the number of passes applied mainly determined polydispersion. {alpha}-Tocopherol was used as a model drug to illustrate release properties of LNP as a function of particle size, which was optimized by the regression models. This study is intended as a first step to optimize production conditions prior to LNP production at both laboratory and industrial scale from an eminently practical approach, based on parameters extensively used in formulation.

  13. Statistical analysis of solid lipid nanoparticles produced by high-pressure homogenization: a practical prediction approach

    International Nuclear Information System (INIS)

    Durán-Lobato, Matilde; Enguix-González, Alicia; Fernández-Arévalo, Mercedes; Martín-Banderas, Lucía

    2013-01-01

    Lipid nanoparticles (LNPs) are a promising carrier for all administration routes due to their safety, small size, and high loading of lipophilic compounds. Among the LNP production techniques, the easy scale-up, lack of organic solvents, and short production times of the high-pressure homogenization technique (HPH) make this method stand out. In this study, a statistical analysis was applied to the production of LNP by HPH. Spherical LNPs with mean size ranging from 65 nm to 11.623 μm, negative zeta potential under –30 mV, and smooth surface were produced. Manageable equations based on commonly used parameters in the pharmaceutical field were obtained. The lipid to emulsifier ratio (R L/S ) was proved to statistically explain the influence of oil phase and surfactant concentration on final nanoparticles size. Besides, the homogenization pressure was found to ultimately determine LNP size for a given R L/S , while the number of passes applied mainly determined polydispersion. α-Tocopherol was used as a model drug to illustrate release properties of LNP as a function of particle size, which was optimized by the regression models. This study is intended as a first step to optimize production conditions prior to LNP production at both laboratory and industrial scale from an eminently practical approach, based on parameters extensively used in formulation.

  14. Long-acting lipidated analogue of human pancreatic polypeptide is slowly released into circulation

    DEFF Research Database (Denmark)

    Bellmann-Sickert, Kathrin; Elling, Christian E; Madsen, Andreas N

    2011-01-01

    The main disadvantages of peptide pharmaceuticals are their rapid degradation and excretion, their low hydrophilicity, and low shelf lifes. These bottlenecks can be circumvented by acylation with fatty acids (lipidation) or polyethylene glycol (PEGylation). Here, we describe the modification....... Lipidation resulted in prolonged action of the hPP analogue in respect of reducing food intake in mice after subcutaneous administration. Therefore, the lipidated hPP analogue could constitute a potential new therapeutic agent against obesity....

  15. Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies

    DEFF Research Database (Denmark)

    Gomes, M. J.; Martins, S.; Ferreira, D.

    2014-01-01

    with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil...... less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded...... with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics indicating their suitability for dermal delivery of anti-alopecia active compounds....

  16. A review and perspective of existing research on the release of nanomaterials from solid nanocomposites.

    Science.gov (United States)

    Froggett, Stephan J; Clancy, Shaun F; Boverhof, Darrell R; Canady, Richard A

    2014-04-07

    Advances in adding nanomaterials to various matrices have occurred in tandem with the identification of potential hazards associated with exposure to pure forms of nanomaterials. We searched multiple research publication databases and found that, relative to data generated on potential nanomaterial hazards or exposures, very little attention has focused on understanding the potential and conditions for release of nanomaterials from nanocomposites. However, as a prerequisite to exposure studying release is necessary to inform risk assessments. We identified fifty-four studies that specifically investigated the release of nanomaterials, and review them in the following release scenario groupings: machining, weathering, washing, contact and incineration. While all of the identified studies provided useful information, only half were controlled experiments. Based on these data, the debris released from solid, non-food nanocomposites contains in varying frequencies, a mixture of four types of debris. Most frequently identified are (1) particles of matrix alone, and slightly less often, the (2) matrix particles exhibit the nanomaterial partially or fully embedded; far less frequently is (3) the added nanomaterial entirely dissociated from the matrix identified: and most rare are (4) dissolved ionic forms of the added nanomaterial. The occurrence of specific debris types appeared to be dependent on the specific release scenario and environment. These data highlight that release from nanocomposites can take multiple forms and that additional research and guidance would be beneficial, allowing for more consistent characterization of the release potential of nanomaterials. In addition, these data support calls for method validation and standardization, as well as understanding how laboratory release scenarios relate to real-world conditions. Importantly, as risk is considered to be a function of the inherent hazards of a substance and the actual potential for exposure, data

  17. Pharmacological characterization of lipidized analogs of prolactin-releasing peptide with a modified C-terminal aromatic ring

    Czech Academy of Sciences Publication Activity Database

    Pražienková, Veronika; Tichá, Anežka; Blechová, Miroslava; Špolcová, Andrea; Železná, Blanka; Maletínská, Lenka

    2016-01-01

    Roč. 67, č. 1 (2016), s. 121-128 ISSN 0867-5910 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * blood-brain barrier * food intake * lipidization * phenylalanine derivatives Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.883, year: 2016 http://www.jpp.krakow.pl/journal/archive/02_16/articles/11_article.html

  18. Preparation, characterization and evaluation of moisturizing and UV protecting effects of topical solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Shiva Golmohammadzadeh

    2012-12-01

    Full Text Available Solid lipid nanoparticles (SLN were recently proposed as carriers for various pharmaceutical and cosmetic actives. These lipid nanoparticles can act as moisturizers and physical sunscreens on their own. Therefore, the full potential of these carriers has yet to be determined. The present study was aimed to determine and compare moisturizing and UV-protecting effects of different solid lipid nanoparticles (SLN prepared by different solid lipids including Glyceryl monostearate (GMS, Precirol® (P and cetyl palmitate (CP as carrier systems of moisturizers and sunscreens. The influence of the size and matrix crystallinity of the solid lipids on the occlusive factor, skin hydration and UV-protection were evaluated by in vitro and in vivo methods. The SLN were prepared by high-shear homogenization and ultrasound methods. Size, zeta potential and morphological characteristics of the samples were assessed by transmission electron microscopy (TEM and thermotropic properties with differential scanning calorimetry (DSC technique. Results of the assessments showed that SLN-CP significantly increases skin hydration and UV-protection, compared to SLN-GMS and SLN-P. It was demonstrated that the size of SLN, crystallinity index of solid lipid in SLN and probably other mechanisms besides the occlusive factor can influence skin hydration and UV-protection indices. Furthermore, findings of the assessments demonstrated significant difference between in vitro and in vivo assessments regarding occlusive factor and moisturizing effects. Findings of the present study indicate that the SLN-CP could be a promising carrier for sunscreens and moisturizers.Nanopartículas lipídicas sólidas (NLS foram, recentemente, propostas como carreadores de vários ativos cosméticos e farmacêuticos. Essas nanopartículas lipídicas podem atuar como hidratantes e protetores solares físicos por si só. Assim sendo, determinou-se o potencial desses carreadores. Os objetivos do

  19. Docetaxel-loaded solid lipid nanoparticles suppress breast cancer cells growth with reduced myelosuppression toxicity

    Directory of Open Access Journals (Sweden)

    Yuan Q

    2014-10-01

    Full Text Available Qing Yuan,1 Jing Han,1,2 Wenshu Cong,1 Ying Ge,3 Dandan Ma,1,3,4 Zhaoxia Dai,3,4 Yaping Li,5 Xiaolin Bi1,3,4 1CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 2School of Life Sciences, Anhui University, Hefei, 3Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 4Graduate School, Dalian Medical University, Dalian, 5Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: Docetaxel is an adjuvant chemotherapy drug widely used to treat multiple solid tumors; however, its toxicity and side effects limit its clinical efficacy. Herein, docetaxel-loaded solid lipid nanoparticles (DSNs were developed to reduce systemic toxicity of docetaxel while still keeping its anticancer activity. To evaluate its anticancer activity and toxicity, and to understand the molecular mechanisms of DSNs, different cellular, molecular, and whole genome transcription analysis approaches were utilized. The DSNs showed lower cytotoxicity compared with the commercial formulation of docetaxel (Taxotere® and induced more apoptosis at 24 hours after treatment in vitro. DSNs can cause the treated cancer cells to arrest in the G2/M phase in a dose-dependent manner similar to Taxotere. They can also suppress tumor growth very effectively in a mice model with human xenograft breast cancer. Systemic analysis of gene expression profiles by microarray and subsequent verification experiments suggested that both DSNs and Taxotere regulate gene expression and gene function, including DNA replication, DNA damage response, cell proliferation, apoptosis, and cell cycle regulation. Some of these genes expressed differentially at the protein level although their messenger RNA expression level was similar under Taxotere and DSN treatment. Moreover, DSNs improved the main side effect of Taxotere by greatly

  20. 3He release characteristics of metal tritides and scandium--tritium solid solutions

    International Nuclear Information System (INIS)

    Perkins, W.G.; Kass, W.J.; Beavis, L.C.

    1976-01-01

    Tritides of such metals as Sc, Ti, and Er are useful materials for determining the effects of He accumulation in metallic solids, for example, CTR first wall materials. Such effects include lattice strain and gross deformation which are related to 3 He retention and ultimate release. Long term gas release studies have indicated that, during the early life of a metal ditritide, a large fraction of the 3 He is retained in the solid. At more advanced ages, the 3 He release rate becomes comparable to the generation rate. Statistical analysis of the data indicates that the acceleration in 3 He release rate depends on accumulated 3 He concentration rather than strictly on age. 3 He outgassing results are presented for thin films of ScT 2 , TiT 2 , and ErT 2 , and the critical 3 He concentrations are discussed in terms of a percolation model. Phase transformations which occur on tritide formation cast some doubt on the validity of extrapolating results obtained for metal tritides to predictions regarding the accumulation of helium in metals. Sc is unique among the early transition and rare-earth metals in that the metal exhibits a very high room temperature T solubility (T/Sc = 0.4) with no phase transformation. Indeed, even the lattice parameters of the hcp Sc lattice are only minimally changed by T solution. Single crystal ScT/sub 0.3/ samples in two crystallographic orientations were obtained. Using a very sensitive technique, 3 He emission was measured from both these samples, as well as from fine-grained thin film Sc--T solid solution samples (ScT/sub 0.3-0.4/). The fine-grained film samples release 3 He at 2-3 percent of the generation rate, while the emission rate from the single-crystal samples is approximately 0.05 percent of the generation rate, indicating a strong grain size effect

  1. The mechanisms of drug release from solid dispersions in water-soluble polymers.

    Science.gov (United States)

    Craig, Duncan Q M

    2002-01-14

    Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. However, despite the publication of numerous original papers and reviews on the subject, the mechanisms underpinning the observed improvements in dissolution rate are not yet understood. In this review the current consensus with regard to the solid-state structure and dissolution properties of solid dispersions is critically assessed. In particular the theories of carrier- and drug-controlled dissolution are highlighted. A model is proposed whereby the release behaviour from the dispersions may be understood in terms of the dissolution or otherwise of the drug into the concentrated aqueous polymer layer adjacent to the solid surface, including a derivation of an expression to describe the release of intact particles from the dispersions. The implications of a deeper understanding of the dissolution mechanisms are discussed, with particular emphasis on optimising the choice of carrier and manufacturing method and the prediction of stability problems.

  2. Loss of covalently linked lipid as the mechanism for radiation-induced release of membrane-bound polysaccharide and exonuclease from Micrococcus radiodurans

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.

    1981-01-01

    The mechanism of γ-radiation-induced release of polysaccharide and exonuclease from the midwall membrane of Micrococcus radiodurans has been examined. These two components appear to be released independently, but by very similar processes. Direct analysis of radiation-released polysaccharide indicated the absence of an alkali-labile neutral lipid normally present in the native material. Radiation-induced release therefore probably results from the radiolytic cleavage of a covalently linked lipid which normally serves to anchor these substances to the membrane. The absence of a natural membrane-bound carotenoid had no effect on the rate of release of these components. Likewise, the absence of exonuclease in an exonuclease minus mutant did not influence the release of polysaccharide. It is suggested that the major pathway of radical transfer from the initiating .OH and culminating in the cleavage of the neutral lipid anchor may not be via the membrane

  3. Targeting the Endocannabinoid/CB1 Receptor System For Treating Major Depression Through Antidepressant Activities of Curcumin and Dexanabinol-Loaded Solid Lipid Nanoparticles

    Directory of Open Access Journals (Sweden)

    Xiaolie He

    2017-08-01

    Full Text Available Background/Aims: This study investigated the underlying mechanisms of the antidepressant effects of curcumin and dexanabinol-loaded solid lipid nanoparticles in corticosterone-induced cell and mice depression models. Methods: Curcumin and dexanabinol-loaded solid lipid nanoparticles (Cur/SLNs-HU-211 were synthesized via an emulsifcation and low-temperature solidification method. Antidepressant activities of nanoparticles in a corticosterone-induced major depression model were investigated by MTT assay, cellular uptake by flow cytometry, behaviour by Forced Swimming Test and rotarod test, neurotransmitters by High Performance Liquid Chromatography, Western blotting, qPCR and immunofluorescence. Results: Treatment with Cur/SLNs-HU-211 induced greater dopamine (DA/5-hydroxytryptamine (5-HT release with reduced corticosterone-induced apoptotic cell death in PC12 cells. Additionally, in vivo Cur/SLNs-HU-211 significantly induced recovery from depressive behaviour with increased DA/5-HT levels, CB1 mRNA levels and CB1, p-MEK1 and p-ERK1/2 protein expression levels in the hippocampus and striatum. Cur/SLNs-HU-211 improved CB1 expression and inspired the proliferation of astrocytes in the hippocampus and striatum, exerted neuroprotective effects by preventing corticosterone -induced BDNF/NeuN expression reduction. Conclusion: Our study implies that Cur/SLNs-HU-211 may be a useful approach for treatment of major depression.

  4. Surface modification of solid lipid nanoparticles for oral delivery of curcumin: Improvement of bioavailability through enhanced cellular uptake, and lymphatic uptake.

    Science.gov (United States)

    Baek, Jong-Suep; Cho, Cheong-Weon

    2017-08-01

    Curcumin has been reported to exhibit potent anticancer effects. However, poor solubility, bioavailability and stability of curcumin limit its in vivo efficacy for the cancer treatment. Solid lipid nanoparticles (SLN) are a promising delivery system for the enhancement of bioavailability of hydrophobic drugs. However, burst release of drug from SLN in acidic environment limits its usage as oral delivery system. Hence, we prepared N-carboxymethyl chitosan (NCC) coated curcumin-loaded SLN (NCC-SLN) to inhibit the rapid release of curcumin in acidic environment and enhance the bioavailability. The NCC-SLN exhibited suppressed burst release in simulated gastric fluid while sustained release was observed in simulated intestinal fluid. Furthermore, NCC-SLN exhibited increased cytotoxicity and cellular uptake on MCF-7 cells. The lymphatic uptake and oral bioavailability of NCC-SLN were found to be 6.3-fold and 9.5-fold higher than that of curcumin solution, respectively. These results suggest that NCC-SLN could be an efficient oral delivery system for curcumin. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

    Energy Technology Data Exchange (ETDEWEB)

    Anantachaisilp, Suranan; Smith, Siwaporn Meejoo [Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400 (Thailand); Treetong, Alongkot; Ruktanonchai, Uracha Rungsardthong [National Nanotechnology Center, National Science and Technology Development Agency, 111 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, Pathumthani 12120 (Thailand); Pratontep, Sirapat [College of KMITL Nanotechnology, King Mongkut' s Institute of Technology Ladkrabang, Bangkok (Thailand); Puttipipatkhachorn, Satit, E-mail: uracha@nanotec.or.th [Department of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400 (Thailand)

    2010-03-26

    Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of {gamma}-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812 as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the {gamma}-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance ({sup 1}H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the {sup 1}H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of {gamma}-oryzanol inside the lipid nanoparticles, the {sup 1}H-NMR revealed that the chemical shifts of the liquid lipid in {gamma}-oryzanol loaded systems were found at rather higher field than those in {gamma}-oryzanol free systems, suggesting incorporation of {gamma}-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of {gamma}-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models

  6. Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

    Science.gov (United States)

    Anantachaisilp, Suranan; Meejoo Smith, Siwaporn; Treetong, Alongkot; Pratontep, Sirapat; Puttipipatkhachorn, Satit; Rungsardthong Ruktanonchai, Uracha

    2010-03-01

    Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of γ-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812® as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the γ-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance (1H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the 1H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of γ-oryzanol inside the lipid nanoparticles, the 1H-NMR revealed that the chemical shifts of the liquid lipid in γ-oryzanol loaded systems were found at rather higher field than those in γ-oryzanol free systems, suggesting incorporation of γ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of γ-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of γ-oryzanol and

  7. Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

    International Nuclear Information System (INIS)

    Anantachaisilp, Suranan; Smith, Siwaporn Meejoo; Treetong, Alongkot; Ruktanonchai, Uracha Rungsardthong; Pratontep, Sirapat; Puttipipatkhachorn, Satit

    2010-01-01

    Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of γ-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812 as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the γ-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance ( 1 H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the 1 H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of γ-oryzanol inside the lipid nanoparticles, the 1 H-NMR revealed that the chemical shifts of the liquid lipid in γ-oryzanol loaded systems were found at rather higher field than those in γ-oryzanol free systems, suggesting incorporation of γ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of γ-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of γ-oryzanol and

  8. Extended-release niacin/laropiprant significantly improves lipid levels in type 2 diabetes mellitus irrespective of baseline glycemic control

    Directory of Open Access Journals (Sweden)

    Bays HE

    2015-02-01

    Full Text Available Harold E Bays,1 Eliot A Brinton,2 Joseph Triscari,3 Erluo Chen,3 Darbie Maccubbin,3 Alexandra A MacLean,3 Kendra L Gibson,3 Rae Ann Ruck,3 Amy O Johnson-Levonas,3 Edward A O’Neill,3 Yale B Mitchel3 1Louisville Metabolic & Atherosclerosis Research Center (L-MARC, Louisville, KY, USA; 2Utah Foundation for Biomedical Research, Salt Lake City, UT, USA; 3Merck & Co, Inc., Whitehouse Station, NJ, USA Background: The degree of glycemic control in patients with type 2 diabetes mellitus (T2DM may alter lipid levels and may alter the efficacy of lipid-modifying agents. Objective: Evaluate the lipid-modifying efficacy of extended-release niacin/laropiprant (ERN/LRPT in subgroups of patients with T2DM with better or poorer glycemic control. Methods: Post hoc analysis of clinical trial data from patients with T2DM who were randomized 4:3 to double-blind ERN/LRPT or placebo (n=796, examining the lipid-modifying effects of ERN/LRPT in patients with glycosylated hemoglobin or fasting plasma glucose levels above and below median baseline levels. Results: At Week 12 of treatment, ERN/LRPT significantly improved low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C, non-high-density lipoprotein cholesterol, triglycerides, and lipoprotein (a, compared with placebo, with equal efficacy in patients above or below median baseline glycemic control. Compared with placebo, over 36 weeks of treatment more patients treated with ERN/LRPT had worsening of their diabetes and required intensification of antihyperglycemic medication, irrespective of baseline glycemic control. Incidences of other adverse experiences were generally low in all treatment groups. Conclusion: The lipid-modifying effects of ERN/LRPT are independent of the degree of baseline glycemic control in patients with T2DM (NCT00485758. Keywords: lipid-modifying agents, hyperglycemia, LDL, HDL, triglycerides

  9. The effect of cetyl palmitate crystallinity on physical properties of gamma-oryzanol encapsulated in solid lipid nanoparticles.

    Science.gov (United States)

    Ruktanonchai, Uracha; Limpakdee, Surachai; Meejoo, Siwaporn; Sakulkhu, Usawadee; Bunyapraphatsara, Nuntavan; Junyaprasert, Varaporn; Puttipipatkhachorn, Satit

    2008-03-05

    This present study was aimed at investigating the effect of the crystallinity of cetyl palmitate based solid lipid nanoparticles (SLNs) on the physical properties of γ-oryzanol-loaded SLNs. SLNs consisting of varying ratios of cetyl palmitate and γ-oryzanol were prepared. Their hydrodynamic diameters were in the range 210-280 nm and the zeta potentials were in the range -27 to -35 mV. The size of SLNs increased as the amount of cetyl palmitate decreased whereas no significant change of zeta potentials was found. Atomic force microscopy pictures indicated the presence of disc-like particles. The crystallinity of SLNs, determined by differential scanning calorimetry and powder x-ray diffraction, was directly dependent on the ratio of cetyl palmitate to γ-oryzanol and decreased with decreasing cetyl palmitate content in the lipid matrix. Varying this ratio in the lipid mix resulted in a shift in the melting temperature and enthalpy, although the SLN structure remained unchanged as an orthorhombic lamellar lattice. This has been attributed to a potential inhibition by γ-oryzanol during lipid crystal growth as well as a less ordered structure of the SLNs. The results revealed that the crystallinity of the SLNs was mainly dependent on the solid lipid, and that the crystallinity has an important impact on the physical characteristics of active-loaded SLNs.

  10. The effect of cetyl palmitate crystallinity on physical properties of gamma-oryzanol encapsulated in solid lipid nanoparticles

    International Nuclear Information System (INIS)

    Ruktanonchai, Uracha; Sakulkhu, Usawadee; Limpakdee, Surachai; Meejoo, Siwaporn; Bunyapraphatsara, Nuntavan; Junyaprasert, Varaporn; Puttipipatkhachorn, Satit

    2008-01-01

    This present study was aimed at investigating the effect of the crystallinity of cetyl palmitate based solid lipid nanoparticles (SLNs) on the physical properties of γ-oryzanol-loaded SLNs. SLNs consisting of varying ratios of cetyl palmitate and γ-oryzanol were prepared. Their hydrodynamic diameters were in the range 210-280 nm and the zeta potentials were in the range -27 to -35 mV. The size of SLNs increased as the amount of cetyl palmitate decreased whereas no significant change of zeta potentials was found. Atomic force microscopy pictures indicated the presence of disc-like particles. The crystallinity of SLNs, determined by differential scanning calorimetry and powder x-ray diffraction, was directly dependent on the ratio of cetyl palmitate to γ-oryzanol and decreased with decreasing cetyl palmitate content in the lipid matrix. Varying this ratio in the lipid mix resulted in a shift in the melting temperature and enthalpy, although the SLN structure remained unchanged as an orthorhombic lamellar lattice. This has been attributed to a potential inhibition by γ-oryzanol during lipid crystal growth as well as a less ordered structure of the SLNs. The results revealed that the crystallinity of the SLNs was mainly dependent on the solid lipid, and that the crystallinity has an important impact on the physical characteristics of active-loaded SLNs

  11. Histological assessment of follicular delivery of flutamide by solid lipid nanoparticles: potential tool for the treatment of androgenic alopecia.

    Science.gov (United States)

    Hamishehkar, Hamed; Ghanbarzadeh, Saeed; Sepehran, Sasan; Javadzadeh, Yousef; Adib, Zahra Mardhiah; Kouhsoltani, Maryam

    2016-01-01

    Flutamide is a potent anti-androgen with the several unwanted side effects in systemic administration, therefore, it has attracted special interest in the development of topically applied formulations for the treatment of androgenic alopecia. The purpose of this study was to prepare and characterize the solid lipid nanoparticles (SLNs) of Flutamide for follicular targeting in the treatment of the androgenic alopecia. Flutamide-loaded SLNs, promising drug carriers for topical application were prepared by hot melt homogenization method. Drug permeation and accumulation in the exercised rat skin and histological study on the male hamsters were performed to assess drug delivery efficiency in vitro and in vivo, respectively. The optimized Flutamide-loaded SLNs (size 198 nm, encapsulation efficiency percentage 65% and loading efficiency percentage 3.27%) exhibited a good stability during the period of at least 2 months. The results of X-ray diffraction showed Flutamide amorphous state confirming uniform drug dispersion in the SLNs structure. Higher skin drug deposition (1.75 times) of SLN formulation compared to Flutamide hydroalcoholic solution represented better localization of the drug in the skin. The in vivo studies showed more new hair follicle growth by utilizing Flutamide-loaded SLNs than Flutamide hydroalcoholic solution which could be due to the higher accumulation of SLNs in the hair follicles as well as slowly and continues release of the Flutamide through the SLNs maximizing hair follicle exposure by antiandrogenic drug. It was concluded Flutamide-loaded SLN formulation can be used as a promising colloidal drug carriers for topical administration of Flutamide in the treatment of androgenic alopecia.

  12. Preparation, characterization, and pharmacokinetics of tilmicosin- and florfenicol-loaded hydrogenated castor oil-solid lipid nanoparticles.

    Science.gov (United States)

    Ling, Z; Yonghong, L; Changqing, S; Junfeng, L; Li, Z; Chunyu, J; Xianqiang, L

    2017-06-01

    To effectively control bovine mastitis, tilmicosin (TIL)- and florfenicol (FF)-loaded solid lipid nanoparticles (SLN) with hydrogenated castor oil (HCO) were prepared by a hot homogenization and ultrasonication method. In vitro antibacterial activity, properties, and pharmacokinetics of the TIL-FF-SLN were studied. The results demonstrated that TIL and FF had a synergistic or additive antibacterial activity against Streptococcus dysgalactiae, Streptococcus uberis, and Streptococcus agalactiae. The size, polydispersity index, and zeta potential of nanoparticles were 289.1 ± 13.7 nm, 0.31 ± 0.05, and -26.7 ± 1.3 mV, respectively. The encapsulation efficiencies for TIL and FF were 62.3 ± 5.9% and 85.1 ± 5.2%, and the loading capacities for TIL and FF were 8.2 ± 0.6% and 3.3 ± 0.2%, respectively. The TIL-FF-SLN showed no irritation in the injection site and sustained release in vitro. After medication, TIL and FF could maintain about 0.1 μg/mL for 122 and 6 h. Compared to the control solution, the SLN increased the area under the concentration-time curve (AUC 0-t ), elimination half-life (T ½ke ), and mean residence time (MRT) of TIL by 33.09-, 23.29-, and 37.53-fold, and 1.69-, 5.00-, and 3.83-fold for FF, respectively. These results of this exploratory study suggest that the HCO-SLN could be a useful system for the delivery of TIL and FF for bovine mastitis therapy. © 2016 John Wiley & Sons Ltd.

  13. Chitosan-solid lipid nanoparticles as carriers for topical delivery of tretinoin.

    Science.gov (United States)

    Ridolfi, Daniela M; Marcato, Priscyla D; Justo, Giselle Z; Cordi, Lívia; Machado, Daisy; Durán, Nelson

    2012-05-01

    Tretinoin (TRE) or all-trans retinoic acid is employed in the topical treatment of various skin diseases including acne and psoriasis. However, its use is strongly limited by side effects and high chemical instability. TRE encapsulation in nanostructured systems reduces these problems. Chitosan is a biopolymer that exhibits a number of interesting properties such as bioadhesion and antibacterial activity. The aim of this work was to prepare and characterize solid lipid nanoparticles (SLN) containing TRE, with and without addition of chitosan, to assess their in vitro cytotoxicity in keratinocytes and to evaluate their antibacterial activity against bacteria related to acne. SLN without (SLN-TRE) and with (SLN-chitosan-TRE) chitosan were prepared by hot high pressure homogenization. The hydrodynamic mean diameter and zeta potential were 162.7±1.4 nm and -31.9±2.0 mV for SLN-TRE, and 284.8±15.0 nm and 55.9±3.1 mV for SLN-chitosan-TRE. The SLN-chitosan-TRE exhibited high encapsulation efficiency, high physical stability in the tested period (one year), were not cytotoxic to keratinocytes and showed high antibacterial activity against P. acnes and S. aureus. Therefore chitosan-SLN can be good candidates to encapsulate TRE and to increase its therapeutic efficacy in the topical treatment of acne. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Solid Lipid Nanoparticles: A Potential Multifunctional Approach towards Rheumatoid Arthritis Theranostics

    Directory of Open Access Journals (Sweden)

    João Albuquerque

    2015-06-01

    Full Text Available Rheumatoid arthritis (RA is the most common joint-related autoimmune disease and one of the most severe. Despite intensive investigation, the RA inflammatory process remains largely unknown and finding effective and long lasting therapies that specifically target RA is a challenging task. This study proposes a different approach for RA therapy, taking advantage of the new emerging field of nanomedicine to develop a targeted theranostic system for intravenous administration, using solid lipid nanoparticles (SLN, a biocompatible and biodegradable colloidal delivery system, surface-functionalized with an anti-CD64 antibody that specifically targets macrophages in RA. Methotrexate (MTX and superparamagnetic iron oxide nanoparticles (SPIONs were co-encapsulated inside the SLNs to be used as therapeutic and imaging agents, respectively. All the formulations presented sizes under 250 nm and zeta potential values lower than −16 mV, suitable characteristics for intravenous administration. Transmission electron microscopy (TEM photographs indicated that the SPIONs were encapsulated inside the SLN matrix and MTX association efficiency values were higher than 98%. In vitro studies, using THP-1 cells, demonstrated that all formulations presented low cytotoxicity at concentrations lower than 500 μg/mL. It was proven that the proposed NPs were not cytotoxic, that both a therapeutic and imaging agent could be co-encapsulated and that the SLN could be functionalized for a potential future application such as anti-body specific targeting. The proposed formulations are, therefore, promising candidates for future theranostic applications.

  15. Solid lipid nanoparticles mediate non-viral delivery of plasmid DNA to dendritic cells

    Science.gov (United States)

    Penumarthi, Alekhya; Parashar, Deepti; Abraham, Amanda N.; Dekiwadia, Chaitali; Macreadie, Ian; Shukla, Ravi; Smooker, Peter M.

    2017-06-01

    There is an increasing demand for novel DNA vaccine delivery systems, mainly for the non-viral type as they are considered relatively safe. Therefore, solid lipid nanoparticles (SLNs) were investigated for their suitability as a non-viral DNA vaccine delivery system. SLNs were synthesised by a modified solvent-emulsification method in order to study their potential to conjugate with plasmid DNA and deliver them in vitro to dendritic cells using eGFP as the reporter plasmid. The DNA-SLN complexes were characterised by electron microscopy, gel retardation assays and dynamic light scattering. The cytotoxicity assay data supported their biocompatibility and was used to estimate safe threshold concentration resulting in high transfection rate. The transfection efficiency of these complexes in a dendritic cell line was shown to increase significantly compared to plasmid alone, and was comparable to that mediated by lipofectamine. Transmission electron microscopy studies delineated the pathway of cellular uptake. Endosomal escape was observed supporting the mechanism of transfection.

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

    Science.gov (United States)

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

    2017-06-13

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

  17. Myricetin solid lipid nanoparticles: Stability assurance from system preparation to site of action.

    Science.gov (United States)

    Gaber, Dina M; Nafee, Noha; Abdallah, Osama Y

    2017-11-15

    Myricetin - a natural flavonoid - has attracted a great interest due to its antioxidant and free-radical scavenging potential. However, its physicochemical instability critically impairs its dosage form design, evaluation and administration. In an attempt to protect from degradation, MYR was encapsulated into Gelucire-based solid lipid nanoparticles (SLNs). The impact of medium pH, processing temperature and different additives on the drug degradation either in free or nanoencapsulated form was assessed. MYR stability was further monitored in essential biorelevant fluids. Investigations have led to the recommendation that the presence of fat-soluble antioxidant is necessary during SLN preparation to protect the drug at high temperature. Meanwhile, physiological buffers as well as simulated fluids should be supplemented with stabilizers as tween 80 and Poloxamer 407, in addition to water-soluble antioxidant such as sodium sulfite. Interestingly, mucin-containing fluids are suggested to provide better protection to MYR, in contrast, cell culture media do not guarantee MYR stability. The degradation kinetics changed from 1st to 2nd order mechanism after MYR nanoencapsulation. In presence of the aforementioned additives, MYR-SLNs significantly reduced the drug degradation rate constant up to 300-folds and prolonged the half-life time up to 4500-folds compared to free MYR in physiological buffers (One-way ANOVA, p8h with no signs of degradation. The study emphasizes virtuous guidance regarding appropriate nanoencapsulation conditions and evaluation attributes ensuing MYR physicochemical stability. Copyright © 2017. Published by Elsevier B.V.

  18. Evaluating Cytotoxicity of Hyaluronate Targeted Solid Lipid Nanoparticles of Etoposide on SK-OV-3 Cells

    Directory of Open Access Journals (Sweden)

    Parviz Mohammadi Ghalaei

    2014-01-01

    Full Text Available The epithelial ovarian carcinoma is one of the most fatal gynecological cancers. Etoposide is used in treating platinum-resistant ovarian cancer. Sodium hyaluronate is a substance that binds to the CD44 receptors overexpressed in SK-OV-3 cells of epithelial ovarian carcinoma. The aim of the present work was to study the cytotoxicity effect of hyaluronate targeted solid lipid nanoparticles (SLNs of etoposide on SK-OV-3 cells. The cytotoxicity of the targeted and nontargeted SLNs of etoposide was compared to free drug on the SK-OV-3 cells by MTT assay method. The cellular uptake of the targeted and nontargeted nanoparticles containing sodium fluorescein was also studied. The difference of cell vitality between nontargeted nanoparticles and also targeted nanoparticles with free drug was significant. Targeted nanoparticles also caused more toxicity than nontargeted nanoparticles (P<0.05. After 4 hours of incubating, the fluorescence was remarkably higher in the cells treated by targeted SLNs rather than nontargeted ones, and there was no observable fluorescence in cells incubated with pure sodium fluorescein. Hyaluronate targeted SLNs containing etoposide increased the cytotoxicity of etoposide on SK-OV-3 cells which may be a worthwhile potential method for reducing the prescribed dose and systemic side effects of this drug in epithelial ovarian carcinoma.

  19. Oridonin Loaded Solid Lipid Nanoparticles Enhanced Antitumor Activity in MCF-7 Cells

    Directory of Open Access Journals (Sweden)

    Lu Wang

    2014-01-01

    Full Text Available Oridonin (ORI, a famous diterpenoid from Chinese herbal medicine, has drawn rising attention for its remarkable apoptosis and autophagy-inducing activity in human cancer therapy, while clinical application of ORI is limited by its strong hydrophobicity and rapid plasma clearance. The purpose of this study was to evaluate whether the antitumor activity of ORI could be enhanced by loading into solid lipid nanoparticles (SLNs. ORI-loaded SLNs were prepared by hot high pressure homogenization with narrow size distribution and good entrapment efficacy. MTT assay indicated that ORI-loaded SLNs enhanced the inhibition of proliferation against several human cancer cell lines including breast cancer MCF-7 cells, hepatocellular carcinoma HepG 2 cells, and lung carcinoma A549 cells compared with free ORI, while no significant enhancement of toxicity to human mammary epithelial MCF-10A cells was shown. Meanwhile, flow cytometric analysis demonstrated that ORI-SLNs induced more significant cell cycle arrest at S and decreased cell cycle arrest at G1/G0 phase in MCF-7 cells than bulk ORI solution. Hoechst 33342 staining and Annexin V/PI assay indicated that apoptotic rates of cells treated with ORI-loaded SLNs were higher compared with free ORI. In summary, our data indicated that SLNs may be a potential carrier for enhancing the antitumor effect of hydrophobic drug ORI.

  20. Bevacizumab loaded solid lipid nanoparticles prepared by the coacervation technique: preliminary in vitro studies

    Science.gov (United States)

    Battaglia, Luigi; Gallarate, Marina; Peira, Elena; Chirio, Daniela; Solazzi, Ilaria; Giordano, Susanna Marzia Adele; Gigliotti, Casimiro Luca; Riganti, Chiara; Dianzani, Chiara

    2015-06-01

    Glioblastoma, the most common primary brain tumor in adults, has an inauspicious prognosis, given that overcoming the blood-brain barrier is the major obstacle to the pharmacological treatment of brain tumors. As neoangiogenesis plays a key role in glioblastoma growth, the US Food and Drug Administration approved bevacizumab (BVZ), an antivascular endothelial growth factor antibody for the treatment of recurrent glioblastoma in patients whose the initial therapy has failed. In this experimental work, BVZ was entrapped in solid lipid nanoparticles (SLNs) prepared by the fatty-acid coacervation technique, thanks to the formation of a hydrophobic ion pair. BVZ activity, which was evaluated by means of four different in vitro tests on HUVEC cells, increased by 100- to 200-fold when delivered in SLNs. Moreover, SLNs can enhance the permeation of fluorescently labelled BVZ through an hCMEC/D3 cell monolayer—an in vitro model of the blood brain barrier. These results are promising, even if further in vivo studies are required to evaluate the effective potential of BVZ-loaded SLNs in glioblastoma treatment.

  1. Diclofenac sodium-loaded solid lipid nanoparticles prepared by emulsion/solvent evaporation method

    Energy Technology Data Exchange (ETDEWEB)

    Liu Dongfei; Jiang Sunmin [Nanjing Medical University, School of Pharmacy (China); Shen Hong [Nanjing Brain Hospital Affiliated to Nanjing Medical University, Neuro-Psychiatric Institute (China); Qin Shan; Liu Juanjuan; Zhang Qing; Li Rui, E-mail: chongloutougao@gmail.com; Xu Qunwei, E-mail: qunweixu@163.com [Nanjing Medical University, School of Pharmacy (China)

    2011-06-15

    The preparation of solid lipid nanoparticles (SLNs) suffers from the drawback of poor incorporation of water-soluble drugs. The aim of this study was therefore to assess various formulation and process parameters to enhance the incorporation of a water-soluble drug (diclofenac sodium, DS) into SLNs prepared by the emulsion/solvent evaporation method. Results showed that the entrapment efficiency (EE) of DS was increased to approximately 100% by lowering the pH of dispersed phase. The EE of DS-loaded SLNs (DS-SLNs) had been improved by the existence of cosurfactants and increment of PVA concentration. Stabilizers and their combination with PEG 400 in the dispersed phase also resulted in higher EE and drug loading (DL). EE increased and DL decreased as the phospholipid/DS ratio became greater, while the amount of DS had an opposite effect. Ethanol turned out to be the ideal solvent making DS-SLNs. EE and DL of DS-SLNs were not affected by either the stirring speed or the viscosity of aqueous and dispersed phase. According to the investigations, drug solubility in dispersion medium played the most important role in improving EE.

  2. Influence of additives and impurities in sweep gas and solid tritium release behaviour from lithium ceramics (review)

    International Nuclear Information System (INIS)

    Tanaka, Satoru

    1991-01-01

    Tritium release from solid breeding material is affected by small amounts of additives or impurities in the sweep gas or solid itself. Addition of hydrogen or water vapor to the sweep gas is reported to enhance the surface reaction of tritium release. Doping to solid breeder with elements of different valence from lithium has a possibility to improve tritium diffusion in the solid. Surface reaction and migration behavior in bulk are believed to be also affected by impurities in the sweep gas and in the solid. In order to model tritium release behavior in the blanket of fusion reactor, the mechanism of interaction with these additives or impurities must be quantitatively formulated. However, the mechanism of these remains to be elucidated. In this paper effects of these additives and impurities on tritium migration are reviewed. The mechanism of surface reaction for He+H 2 sweep gas is also discussed. (orig.)

  3. Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies

    Directory of Open Access Journals (Sweden)

    Gomes MJ

    2014-03-01

    achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics indicating their suitability for dermal delivery of anti-alopecia active compounds. Keywords: nanostructured lipid carriers (NLC, alopecia, anti-alopecia therapy, minoxidil, finasteride

  4. Mercury speciation in environmental solid samples using thermal release technique with atomic absorption detection

    Energy Technology Data Exchange (ETDEWEB)

    Shuvaeva, Olga V. [Institute of Inorganic Chemistry, Academician Lavrent' ev Prospect 3, 630090 Novosbirsk (Russian Federation)], E-mail: olga@che.nsk.su; Gustaytis, Maria A.; Anoshin, Gennadii N. [Institute of Geology and Mineralogy, Siberian Branch of Russian Academy of Sciences, Koptyug Prospect 3, 630090 Novosibirsk (Russian Federation)

    2008-07-28

    A sensitive and very simple method for determination of mercury species in solid samples has been developed involving thermal release analysis in combination with atomic absorption (AAS) detection. The method allows determination of mercury(II) chloride, methylmercury and mercury sulfide at the level of 0.70, 0.35 and 0.20 ng with a reproducibility of the results of 14, 25 and 18%, respectively. The accuracy of the developed assay has been estimated using certified reference materials and by comparison of the results with those of an independent method. The method has been applied for Hg species determination in original samples of lake sediments and plankton.

  5. Amorphous Solid Dispersion of Epigallocatechin Gallate for Enhanced Physical Stability and Controlled Release.

    Science.gov (United States)

    Cao, Yizheng; Teng, Jing; Selbo, Jon

    2017-11-09

    Epigallocatechin gallate (EGCG) has been recognized as the most prominent green tea extract due to its healthy influences. The high instability and low bioavailability, however, strongly limit its utilization in food and drug industries. This work, for the first time, develops amorphous solid dispersion of EGCG to enhance its bioavailability and physical stability. Four commonly used polymeric excipients are found to be compatible with EGCG in water-dioxane mixtures via a stepwise mixing method aided by vigorous mechanical interference. The dispersions are successfully generated by lyophilization. The physical stability of the dispersions is significantly improved compared to pure amorphous EGCG in stress condition (elevated temperature and relative humidity) and simulated gastrointestinal tract environment. From the drug release tests, one of the dispersions, EGCG-Soluplus ® 50:50 ( w / w ) shows a dissolution profile that only 50% EGCG is released in the first 20 min, and the remains are slowly released in 24 h. This sustained release profile may open up new possibilities to increase EGCG bioavailability via extending its elimination time in plasma.

  6. Amorphous Solid Dispersion of Epigallocatechin Gallate for Enhanced Physical Stability and Controlled Release

    Directory of Open Access Journals (Sweden)

    Yizheng Cao

    2017-11-01

    Full Text Available Epigallocatechin gallate (EGCG has been recognized as the most prominent green tea extract due to its healthy influences. The high instability and low bioavailability, however, strongly limit its utilization in food and drug industries. This work, for the first time, develops amorphous solid dispersion of EGCG to enhance its bioavailability and physical stability. Four commonly used polymeric excipients are found to be compatible with EGCG in water-dioxane mixtures via a stepwise mixing method aided by vigorous mechanical interference. The dispersions are successfully generated by lyophilization. The physical stability of the dispersions is significantly improved compared to pure amorphous EGCG in stress condition (elevated temperature and relative humidity and simulated gastrointestinal tract environment. From the drug release tests, one of the dispersions, EGCG-Soluplus® 50:50 (w/w shows a dissolution profile that only 50% EGCG is released in the first 20 min, and the remains are slowly released in 24 h. This sustained release profile may open up new possibilities to increase EGCG bioavailability via extending its elimination time in plasma.

  7. 3He release characteristics of metal tritides and scandium--tritium solid solutions

    International Nuclear Information System (INIS)

    Perkins, W.G.; Kass, W.J.; Beavis, L.C.

    1975-01-01

    Tritides of such metals as scandium, titanium, and erbium are useful materials for determining the effects of helium accumulation in metallic solids, for example, CTR first wall materials. Such effects include lattice strain and gross deformation, as reported elsewhere, which are related to 3 He retention and ultimate release. Long term gas release studies have indicated that, during the early life of a metal ditritide, a large fraction of the 3 He is retained in the solid. At more advanced ages (2 to 4 years, depending on the parent metal), the 3 He release rate becomes comparable to the generation rate. Statistical analysis of the data indicates that the acceleration in 3 He release rate depends on accumulated 3 He concentration rather than strictly on age. 3 He outgassing results are presented for thin films of ScT 2 , TiT 2 , and ErT 2 , and the critical 3 He concentrations are discussed in terms of a percolation model. Phase transformations which occur on tritide formation cast some doubt on the validity of extrapolating results obtained for metal tritides to predictions regarding the accumulation of helium in metals. Scandium is unique among the early transition and rare-earth metals in that the metal exhibits a very high room temperature tritium solubility (T/Sc = 0.4) with no phase transformation. Indeed, even the lattice parameters of the hcp scandium lattice are only minimally changed by tritium solution, and we have succeeded in obtaining single crystal ScT 0 . 3 samples in two crystallographic orientations. Using a very sensitive technique, we have measured 3 He emission from both these samples, as well as from fine-grained thin film scandium-tritium solid solution samples (ScT 0 . 3 - 0 . 4 ). The fine-grained film samples release 3 He at 2 to 3 percent of the generation rate, while the emission rate from the single-crystal samples is approximately 0.05 percent of the generation rate, indicating a strong grain size effect

  8. Thermo-responsive mesoporous silica/lipid bilayer hybrid nanoparticles for doxorubicin on-demand delivery and reduced premature release.

    Science.gov (United States)

    Zhang, Qing; Chen, Xuanxuan; Shi, Huihui; Dong, Gaoqiu; Zhou, Meiling; Wang, Tianji; Xin, Hongliang

    2017-12-01

    Hybrid nanocarriers based on mesoporous silica nanoparticles (MSNs) and supported lipid bilayer (SLB) have been studied as drug delivery system. It still remains challenges to develop these nanocarriers (SLB-MSNs) with on-demand drug release profile for chemotherapy. Here, we reported the biocompatible SLB-MSNs with high drug loading, which could release doxorubicin (DOX) in response to hyperthermia and reduce premature release. After synthesis of MSNs via a sol-gel procedure, the thermo-responsive SLB was deposited on the MSNs by sonication to completely seal the mesopores. The obtained SLB-MSNs consisted of 50 nm-sized MSN cores and 6.3 nm-thick SLB shells. Due to the big surface and pore volume of MSNs, the high drug loading content (7.30±0.02%) and encapsulation efficiency (91.16±0.28%) were achieved. The SLB blocking the mesopores reduced 50% of premature release and achieved on-demand release in a thermo-responsive manner. Moreover, SLB-MSNs showed good hemocompatibility at any tested concentration (25-700μg/mL), while bare MSNs caused 100% of hemolysis at concentration larger than 325μg/mL. In addition, in vitro U251 cell uptake experiment demonstrated that compared with uncapped MSNs, SLB-MSNs could prevent untargeted cellular uptake of DOX owing to reduced premature release and steric hindrance of PEG, which would be beneficial to minimize toxicity for healthy tissues. These results indicated that SLB-MSNs with thermo-responsive release capacity possessed great potential in future synergistic thermo-chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Evaluation of radiolabeled curcumin-loaded solid lipid nanoparticles usage as an imaging agent in liver-spleen scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Ayan, Arif Kursad [Department of Nuclear Medicine, Ataturk University, 25240 Erzurum (Turkey); Yenilmez, Ayse, E-mail: yenilmez2014@gmail.com [Department of Nanoscience and Nanoengineering, Ataturk University, 25240 Erzurum (Turkey); Department of Molecular Biology and Genetics, Erzurum Technical University, 25240 Erzurum (Turkey); Eroglu, Hayrettin [Department of Biomedical Engineering, Ataturk University, 25240 Erzurum (Turkey)

    2017-06-01

    Curcumin-loaded solid lipid nanoparticles (C-SLNs) were prepared using micro emulsion and ultrasonication methods in the first stage of this study to determine the role of C-SLN on liver-spleen scintigraphy. It was concluded that the curcumin that was encapsulated in solid lipid nanoparticles had a β′ polymorph structure according to the X-ray diffraction (XRD) analysis. İt was concluded that these particles were at nano scale according to the laser diffraction (LD) analysis. Fourier transform infrared spectroscopy (FT-IR) analysis suggested an interaction between the curcumin and the solid lipid matrix, and the curcumin was loaded on the solid lipid nanoparticles. Moreover, the particles were concluded to be spherical and at nanoscale according to the scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images. On the other hand, thermogravimetric analysis (TGA) suggested that the curcumin loaded solid nanoparticles were stable against the temperature. C-SLNs were labeled with Technetium-99 m ({sup 99m}Tc) radioisotope in the second stage of the study, then using scintigraphic methods in-vivo studies were performed on New Zealand rabbit and made a comparison with Phytate colloid, routinely used in liver-spleen scintigraphy. After analyzing the images and the biological distributions obtained from the experiments, uptake was observed in the liver and the spleen. Following from the experiment results, {sup 99m}Tc-labeled C-SLNs was concluded to be a possible imaging agent. In particular, it could be a new radiopharmaceutical alternative to {sup 99m}Tc-labeled compounds that are used in liver and spleen imaging in colloid scintigraphy. - Graphıcal abstract: Display Omitted - Hıghlıghts: • Curcumin-loaded solid lipid nanoparticles (C-SLNs) were prepared and examined characterization studies. • The C-SLNs were labeled with {sup 99m}Tc and made a comparison with Phytate colloid, routinely used in liver-spleen scintigraphy. • In vivo

  10. Releasing Stored Solar Energy within Pond Scum: Biodiesel from Algal Lipids

    Science.gov (United States)

    Blatti, Jillian L.; Burkart, Michael D.

    2012-01-01

    Microalgae have emerged as an attractive feedstock for the mass production of renewable transportation fuels due to their fast growth rate, flexible habitat preferences, and substantial oil yields. As an educational tool, a laboratory was developed that mimics emerging algal biofuel technology, including the extraction of algal lipids and…

  11. Analysis of Solid and Aqueous Phase Products from Hydrothermal Carbonization of Whole and Lipid-Extracted Algae

    Directory of Open Access Journals (Sweden)

    Amber Broch

    2013-12-01

    Full Text Available Microalgae have tremendous potential as a feedstock for production of liquid biofuels, particularly biodiesel fuel via transesterification of algal lipids. However, biodiesel production results in significant amounts of algal residues, or “lipid extracted algae” (LEA. Suitable utilization of the LEA residue will improve the economics of algal biodiesel. In the present study, we evaluate the hydrothermal carbonization (HTC of whole and lipid extracted algal (Spirulina maxima feedstocks in order to produce a solid biofuel (hydrochar and value-added co-products in the aqueous phase. HTC experiments were performed using a 2-L Parr reactor (batch type at 175–215 °C with a 30-min holding time. Solid, aqueous and gaseous products were analyzed using various laboratory methods to evaluate the mass and carbon balances, and investigate the existence of high value chemicals in the aqueous phase. The HTC method is effective in creating an energy dense, solid hydrochar from both whole algae and LEA at lower temperatures as compared to lignocellulosic feedstocks, and is effective at reducing the ash content in the resulting hydrochar. However, under the treatment temperatures investigated, less than 1% of the starting dry algae mass was recovered as an identified high-value chemical in the aqueous phase.

  12. Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Amoxicillin Trihydrate.

    Science.gov (United States)

    Thambavita, Dhanusha; Galappatthy, Priyadarshani; Mannapperuma, Uthpali; Jayakody, Lal; Cristofoletti, Rodrigo; Abrahamsson, Bertil; Groot, Dirk W; Langguth, Peter; Mehta, Mehul; Parr, Alan; Polli, James E; Shah, Vinod P; Dressman, Jennifer

    2017-10-01

    Literature and experimental data relevant to waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release solid oral dosage forms containing amoxicillin trihydrate are reviewed. Solubility and permeability characteristics according to the Biopharmaceutics Classification System (BCS), therapeutic uses, therapeutic index, excipient interactions, as well as dissolution and BE and bioavailability studies were taken into consideration. Solubility and permeability studies indicate that amoxicillin doses up to 875 mg belong to BCS class I, whereas 1000 mg belongs to BCS class II and doses of more than 1000 mg belong to BCS class IV. Considering all aspects, the biowaiver procedure can be recommended for solid oral products of amoxicillin trihydrate immediate-release preparations containing amoxicillin as the single active pharmaceutical ingredient at dose strengths of 875 mg or less, provided (a) only the excipients listed in this monograph are used, and only in their usual amounts, (b) the biowaiver study is performed according to the World Health Organization-, U.S. Food and Drug Administration-, or European Medicines Agency-recommended method using the innovator as the comparator, and (c) results comply with criteria for "very rapidly dissolving" or "similarly rapidly dissolving." Products containing other excipients and those containing more than 875 mg amoxicillin per unit should be subjected to an in vivo BE study. Copyright © 2017 American Pharmacists Association®. All rights reserved.

  13. Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Folic Acid.

    Science.gov (United States)

    Hofsäss, Martin A; Souza, Jacqueline de; Silva-Barcellos, Neila M; Bellavinha, Karime R; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Parr, Alan; Langguth, Peter; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Mehta, Mehul U; Dressman, Jennifer B

    2017-12-01

    This work presents a review of literature and experimental data relevant to the possibility of waiving pharmacokinetic bioequivalence studies in human volunteers for approval of immediate-release solid oral pharmaceutical forms containing folic acid as the single active pharmaceutical ingredient. For dosage forms containing 5 mg folic acid, the highest dose strength on the World Health Organization Essential Medicines List, the dose/solubility ratio calculated from solubility studies was higher than 250 mL, corresponding to a classification as "not highly soluble." Small, physiological doses of folic acid (≤320 μg) seem to be absorbed completely via active transport, but permeability data for higher doses of 1-5 mg are inconclusive. Following a conservative approach, folic acid is classified as a Biopharmaceutics Classification System class IV compound until more reliable data become available. Commensurate with its solubility characteristics, the results of dissolution studies indicated that none of the folic acid products evaluated showed rapid dissolution in media at pH 1.2 or 4.5. Therefore, according to the current criteria of the Biopharmaceutics Classification System, the biowaiver approval procedure cannot be recommended for immediate-release solid oral dosage forms containing folic acid. Copyright © 2017 American Pharmacists Association®. All rights reserved.

  14. Metal releases from a municipal solid waste incineration air pollution control residue mixed with compost.

    Science.gov (United States)

    Van Praagh, M; Persson, K M

    2008-08-01

    The influence of 10 wt.% mature compost was tested on the heavy metal leachate emissions from a calcium-rich municipal solid waste incineration air pollution control residue (MSWI APC). Apart from elongated columns (500 and 1250 mm), an otherwise norm compliant European percolation test setup was used. More than 99% of the metals Al, As, Cd, Cr, Cu, Fe and Ni were left in the APC residue after leaching to a liquid-to-solid ratio (L/S) of 10. Apparent short-term effects of elevated leachate DOC concentrations on heavy metal releases were not detected. Zn and Pb leachate concentrations were one order of magnitude lower for L/S 5 and 10 from the pure APC residue column, which suggests a possible long-term effect of compost on the release of these elements. Prolonging the contact time between the pore water and the material resulted in elevated leachate concentrations at L/S 0.1 to L/S 1 by a factor of 2. Only Cr and Pb concentrations were at their maxima in the first leachates at L/S 0.1. Equilibrium speciation modelling with the PHREEQC code suggested portlandite (Ca(OH)2) to control Ca solubility and pH.

  15. Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride.

    Science.gov (United States)

    Plöger, Gerlinde F; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, Dirk W; Langguth, Peter; Mehta, Mehul U; Parr, Alan; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Dressman, Jennifer B

    2018-07-01

    Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To elucidate the Biopharmaceutics Classification System (BCS) classification, experimental solubility and dissolution studies were also carried out. The antimalarial proguanil hydrochloride, effective via the parent compound proguanil and the metabolite cycloguanil, is not considered to be a narrow therapeutic index drug. Proguanil hydrochloride salt was shown to be highly soluble according to the U.S. Food and Drug Administration, World Health Organization, and European Medicines Agency guidelines, but data for permeability are inconclusive. Therefore, proguanil hydrochloride is conservatively classified as a BCS class 3 substance. In view of this information and the assessment of risks associated with a false positive decision, a BCS-based biowaiver approval procedure can be recommended for orally administered solid immediate release products containing proguanil hydrochloride, provided well-known excipients are used in usual amounts and provided the in vitro dissolution of the test and reference products is very rapid (85% or more are dissolved in 15 min at pH 1.2, 4.5, and 6.8) and is performed according to the current requirements for BCS-based biowaivers. Copyright © 2018 American Pharmacists Association®. All rights reserved.

  16. Curcumin loaded solid lipid nanoparticles ameliorate adjuvant-induced arthritis in rats.

    Science.gov (United States)

    Arora, R; Kuhad, A; Kaur, I P; Chopra, K

    2015-08-01

    Rheumatoid arthritis (RA), a chronic and systemic inflammation, results in destruction of joints and cartilages. Effectiveness of curcumin has been established in a wide variety of inflammatory disorders, but its utility as a therapeutic agent is limited by its poor absorption, rapid metabolism and fast systemic elimination. To apprehend these limitations, we propose to use highly bioavailable curcumin loaded solid lipid nanoparticles (C-SLNs) for the treatment of RA. In the present study, the protective effect of curcumin and its SLNs was evaluated in complete Freund's adjuvant (CFA)-induced arthritis in rats. Arthritic rats exhibited marked decrease in paw withdrawal threshold in Randall-Selitto and von Frey hair test along with decreased reaction time in hot plate. Arthritic rats also showed significant joint hyperalgesia, joint stiffness and increased paw volume along with marked decrease in mobility score. Arthritic rats showed a significant increase in blood leukocyte count, oxidative-nitrosative stress, tumour necrosis factor-α, C-reactive protein, cyclic citrullinated peptide antibody levels and radiological alterations in tibiotarsal joint. C-SLN administration (10 and 30 mg/kg), when compared with free curcumin (10 and 30 mg/kg), significantly and dose dependently ameliorated various symptoms of arthritis in rats, improved biochemical markers and preserved radiological alterations in joints of arthritic rats. The current findings suggest the protective potential of curcumin-SLNs in ameliorating CFA-induced arthritis in rats through attenuation of oxido-inflammatory and immunomodulatory cascade. Further, the results emphasize that SLNs are a novel approach to deliver curcumin into the inflamed joints and improve its biopharmaceutical performance. © 2014 European Pain Federation - EFIC®

  17. Cross-Linking Mast Cell Specific Gangliosides Stimulates the Release of Newly Formed Lipid Mediators and Newly Synthesized Cytokines

    Directory of Open Access Journals (Sweden)

    Edismauro Garcia Freitas Filho

    2016-01-01

    Full Text Available Mast cells are immunoregulatory cells that participate in inflammatory processes. Cross-linking mast cell specific GD1b derived gangliosides by mAbAA4 results in partial activation of mast cells without the release of preformed mediators. The present study examines the release of newly formed and newly synthesized mediators following ganglioside cross-linking. Cross-linking the gangliosides with mAbAA4 released the newly formed lipid mediators, prostaglandins D2 and E2, without release of leukotrienes B4 and C4. The effect of cross-linking these gangliosides on the activation of enzymes in the arachidonate cascade was then investigated. Ganglioside cross-linking resulted in phosphorylation of cytosolic phospholipase A2 and increased expression of cyclooxygenase-2. Translocation of 5-lipoxygenase from the cytosol to the nucleus was not induced by ganglioside cross-linking. Cross-linking of GD1b derived gangliosides also resulted in the release of the newly synthesized mediators, interleukin-4, interleukin-6, and TNF-α. The effect of cross-linking the gangliosides on the MAP kinase pathway was then investigated. Cross-linking the gangliosides induced the phosphorylation of ERK1/2, JNK1/2, and p38 as well as activating both NFκB and NFAT in a Syk-dependent manner. Therefore, cross-linking the mast cell specific GD1b derived gangliosides results in the activation of signaling pathways that culminate with the release of newly formed and newly synthesized mediators.

  18. Resolving Radiological Classification and Release Issues for Many DOE Solid Wastes and Salvageable Materials

    Energy Technology Data Exchange (ETDEWEB)

    Hochel, R.C.

    1999-06-14

    The cost effective radiological classification and disposal of solid materials with potential volume contamination, in accordance with applicable U.S. Department of Energy (DOE) Orders, suffers from an inability to unambiguously distinguish among transuranic waste, low-level waste, and unconditional-release materials. Depending on the classification, disposal costs can vary by a hundred-fold. But in many cases, the issues can be easily resolved by a combination of process information, some simple measurements, and calculational predictions from a computer model for radiation shielding.The proper classification and disposal of many solid wastes requires a measurement regime that is able to show compliance with a variety of institutional and regulatory contamination limits. Although this is not possible for all solid wastes, there are many that do lend themselves to such measures. Several examples are discussed which demonstrate the possibilities, including one which was successfully applied to bulk contamination.The only barriers to such broader uses are the slow-to-change institutional perceptions and procedures. For many issues and materials, the measurement tools are available; they need only be applied.

  19. Resolving Radiological Classification and Release Issues for Many DOE Solid Wastes and Salvageable Materials

    International Nuclear Information System (INIS)

    Hochel, R.C.

    1999-01-01

    The cost effective radiological classification and disposal of solid materials with potential volume contamination, in accordance with applicable U.S. Department of Energy (DOE) Orders, suffers from an inability to unambiguously distinguish among transuranic waste, low-level waste, and unconditional-release materials in a generic way allowing in-situ measurement and verification. Depending on a material''s classification, disposal costs can vary by a hundred-fold. With these large costs at risk, the issues involved in making defensible decisions are ripe for closer scrutiny. In many cases, key issues can be easily resolved by a combination of process information, some simple measurements, and calculational predictions from a computer model for radiation shielding. The proper classification and disposal of many solid wastes requires a measurement regime that is able to show compliance with a variety of institutional and regulatory contamination limits. Ultimate responsibility for this, of course, rests with radiological control or health physics organization of the individual site, but there are many measurements which can be performed by operations and generation organizations to simplify the process and virtually guarantee acceptance. Although this is not possible for all potential solid wastes, there are many that do lend themselves to such measures, particularly some of large volumes and realizable cost savings. Mostly what is needed for this to happen are a few guiding rules, measurement procedures, and cross checks for potential pitfalls. Several examples are presented here and discussed that demonstrate the possibilities, including one which was successfully applied to bulk contamination

  20. Resolving Radiological Classification and Release Issues for Many DOE Solid Wastes and Salvageable Materials

    International Nuclear Information System (INIS)

    Hochel, R.C.

    1999-01-01

    The cost effective radiological classification and disposal of solid materials with potential volume contamination, in accordance with applicable U.S. Department of Energy (DOE) Orders, suffers from an inability to unambiguously distinguish among transuranic waste, low-level waste, and unconditional-release materials. Depending on the classification, disposal costs can vary by a hundred-fold. But in many cases, the issues can be easily resolved by a combination of process information, some simple measurements, and calculational predictions from a computer model for radiation shielding.The proper classification and disposal of many solid wastes requires a measurement regime that is able to show compliance with a variety of institutional and regulatory contamination limits. Although this is not possible for all solid wastes, there are many that do lend themselves to such measures. Several examples are discussed which demonstrate the possibilities, including one which was successfully applied to bulk contamination.The only barriers to such broader uses are the slow-to-change institutional perceptions and procedures. For many issues and materials, the measurement tools are available; they need only be applied

  1. Evaluation of percutaneous absorption of the repellent diethyltoluamide and the sunscreen ethylhexyl p-methoxycinnamate-loaded solid lipid nanoparticles: an in-vitro study.

    Science.gov (United States)

    Puglia, Carmelo; Bonina, Francesco; Castelli, Francesco; Micieli, Dorotea; Sarpietro, Maria Grazia

    2009-08-01

    Diethyltoluamide and ethylhexyl p-methoxycinnamate (OMC) are two active ingredients in insect repellent and sunscreen products, respectively. The concurrent application of these two substances often increases their systemic absorption, compromising the safety and efficiency of the cosmetic product. In this study, diethyltoluamide and OMC were incorporated into solid lipid nanoparticles, a colloidal drug delivery system, to reduce percutaneous absorption and avoid toxic effects and also maintain the efficacy of the two active compounds on the skin surface for a long duration. Solid lipid nanoparticles were prepared based on an ultrasonication technique and characterized by differential scanning calorimetry (DSC) analyses. In-vitro studies determined the percutaneous absorption of diethyltoluamide and OMC. DSC data carried out on unloaded and diethyltoluamide- and/or OMC-loaded solid lipid nanoparticles highlighted that diethyltoluamide and OMC modified the temperature and the enthalpy change associated to the calorimetric peak of solid lipid nanoparticles. The concurrent presence of the two compounds in the solid lipid nanoparticles caused a synergic effect, indicating that the lipid matrix of nanoparticles guaranteed a high encapsulation of both diethyltoluamide and OMC. Results from the in-vitro study demonstrated that the particles were able to reduce the skin permeation of the two cosmetic ingredients in comparison with an oil-in-water emulsion. This study has provided supplementary evidence as to the potential of lipid nanoparticles as carriers for topical administration of cosmetic active compounds.

  2. Solid-state NMR of the Yersinia pestis outer membrane protein Ail in lipid bilayer nanodiscs sedimented by ultracentrifugation

    International Nuclear Information System (INIS)

    Ding, Yi; Fujimoto, L. Miya; Yao, Yong; Marassi, Francesca M.

    2015-01-01

    Solid-state NMR studies of sedimented soluble proteins has been developed recently as an attractive approach for overcoming the size limitations of solution NMR spectroscopy while bypassing the need for sample crystallization or precipitation (Bertini et al. Proc Natl Acad Sci USA 108(26):10396–10399, 2011). Inspired by the potential benefits of this method, we have investigated the ability to sediment lipid bilayer nanodiscs reconstituted with a membrane protein. In this study, we show that nanodiscs containing the outer membrane protein Ail from Yersinia pestis can be sedimented for solid-state NMR structural studies, without the need for precipitation or lyophilization. Optimized preparations of Ail in phospholipid nanodiscs support both the structure and the fibronectin binding activity of the protein. The same sample can be used for solution NMR, solid-state NMR and activity assays, facilitating structure–activity correlation experiments across a wide range of timescales

  3. Solid-state NMR of the Yersinia pestis outer membrane protein Ail in lipid bilayer nanodiscs sedimented by ultracentrifugation

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Yi; Fujimoto, L. Miya; Yao, Yong; Marassi, Francesca M., E-mail: fmarassi@sbmri.org [Sanford-Burnham Medical Research Institute (United States)

    2015-04-15

    Solid-state NMR studies of sedimented soluble proteins has been developed recently as an attractive approach for overcoming the size limitations of solution NMR spectroscopy while bypassing the need for sample crystallization or precipitation (Bertini et al. Proc Natl Acad Sci USA 108(26):10396–10399, 2011). Inspired by the potential benefits of this method, we have investigated the ability to sediment lipid bilayer nanodiscs reconstituted with a membrane protein. In this study, we show that nanodiscs containing the outer membrane protein Ail from Yersinia pestis can be sedimented for solid-state NMR structural studies, without the need for precipitation or lyophilization. Optimized preparations of Ail in phospholipid nanodiscs support both the structure and the fibronectin binding activity of the protein. The same sample can be used for solution NMR, solid-state NMR and activity assays, facilitating structure–activity correlation experiments across a wide range of timescales.

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

    Science.gov (United States)

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

    2017-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Chih-Hung Lin

    2017-04-01

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

  6. Combination of niacin extended-release and simvastatin results in a less atherogenic lipid profile than atorvastatin monotherapy

    Directory of Open Access Journals (Sweden)

    William Insull Jr

    2010-11-01

    Full Text Available William Insull Jr1, Peter P Toth2, H Robert Superko3, Roopal B Thakkar4, Scott Krause4, Ping Jiang4, Rhea A Parreno4, Robert J Padley41Baylor College of Medicine and Methodist Hospital, Houston, Texas; 2University of Illinois College of Medicine, Peoria, Illinois; 3Celera, Alameda, California, Mercer University, Atlanta, Georgia; 4Abbott, Abbott Park, Illinois, USAObjective: To compare the effects of combination niacin extended-release + simvastatin (NER/S versus atorvastatin alone on apolipoproteins and lipid fractions in a post hoc analysis from SUPREME, a study which compared the lipid effects of niacin extended-release + simvastatin and atorvastatin in patients with hyperlipidemia or mixed dyslipidemia.Patients and methods: Patients (n = 137 with dyslipidemia (not previously receiving statin therapy or having discontinued any lipid-altering treatment 4–5 weeks prior to the study received NER/S (1000/40 mg/day for four weeks, then 2000/40 mg/day for eight weeks or atorvastatin 40 mg/day for 12 weeks. Median percent changes in apolipoprotein (apo A-1, apo B, and the apo B:A-I ratio, and nuclear magnetic resonance lipoprotein subclasses from baseline to week 12 were compared using the Wilcoxon rank-sum test and Fisher’s exact test.Results: NER/S treatment produced significantly greater percent changes in apo A-I and apo B:A-I, and, at the final visit, apo B <80 mg/dL was attained by 59% versus 33% of patients, compared with atorvastatin treatment (P = 0.003. NER/S treatment resulted in greater percent reductions in calculated particle numbers for low-density lipoprotein (LDL, 52% versus 43%; P = 0.022, small LDL (55% versus 45%; P = 0.011, very low-density lipoprotein (VLDL and total chylomicrons (63% versus 39%; P < 0.001, and greater increases in particle size for LDL (2.7% versus 1.0%; P = 0.007 and VLDL (9.3% versus 0.1%; P < 0.001, compared with atorvastatin.Conclusion: NER/S treatment significantly improved apo A-I levels and the apo

  7. Delivery of kinesin spindle protein targeting siRNA in solid lipid nanoparticles to cellular models of tumor vasculature

    International Nuclear Information System (INIS)

    Ying, Bo; Campbell, Robert B.

    2014-01-01

    Highlights: • siRNA-lipid nanoparticles are solid particles not lipid bilayers with aqueous core. • High, but not low, PEG content can prevent nanoparticle encapsulation of siRNA. • PEG reduces cellular toxicity of cationic nanoparticles in vitro. • PEG reduces zeta potential while improving gene silencing of siRNA nanoparticles. • Kinesin spindle protein can be an effective target for tumor vascular targeting. - Abstract: The ideal siRNA delivery system should selectively deliver the construct to the target cell, avoid enzymatic degradation, and evade uptake by phagocytes. In the present study, we evaluated the importance of polyethylene glycol (PEG) on lipid-based carrier systems for encapsulating, and delivering, siRNA to tumor vessels using cellular models. Lipid nanoparticles containing different percentage of PEG were evaluated based on their physical chemical properties, density compared to water, siRNA encapsulation, toxicity, targeting efficiency and gene silencing in vitro. siRNA can be efficiently loaded into lipid nanoparticles (LNPs) when DOTAP is included in the formulation mixture. However, the total amount encapsulated decreased with increase in PEG content. In the presence of siRNA, the final formulations contained a mixed population of particles based on density. The major population which contains the majority of siRNA exhibited a density of 4% glucose, and the minor fraction associated with a decreased amount of siRNA had a density less than PBS. The inclusion of 10 mol% PEG resulted in a greater amount of siRNA associated with the minor fraction. Finally, when kinesin spindle protein (KSP) siRNA was encapsulated in lipid nanoparticles containing a modest amount of PEG, the proliferation of endothelial cells was inhibited due to the efficient knock down of KSP mRNA. The presence of siRNA resulted in the formation of solid lipid nanoparticles when prepared using the thin film and hydration method. LNPs with a relatively modest amount of

  8. Modification of ChPL (chitosan protein–lipid nanoparticles for in vitro release of rifampicin (RIF

    Directory of Open Access Journals (Sweden)

    Poopak Farnia

    2015-01-01

    Results and conclusions: The average size of RIF ChPL-NPs was about 50–250nm. The release of RIF from the dialysis bag started after 30 min which was 2400ng/ml; after 16 h the release of RIF was 15,000ng/ml; and at 40 h the concentration reached to 19,600ng/ml. Therefore, these results showed a slow release of RIF from ChPL-NPs. Basically, the intensity of the surface charges in nanoparticle is important as it determines their interaction with bioactive compound. In RIF ChPL-NPs, lipid had negative charges, whereas chitosan and gelatin had positive charges. The electrostatic interaction between oppositely charged ions would ultimately cause an effective system drug delivery. RIF ChPL-NPs is not only suitable for intravenous administration, but it can be used as an inhalation aerosol, because this nanoparticle has a capacity to adhere to mucosal surfaces and transiently open the tight junction.

  9. Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Xie Shuyu

    2011-11-01

    Full Text Available Abstract Background Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Methods Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD50 was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. Results After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. Conclusions The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the

  10. Effect of Anionic Polymers on Drug Loading and Release from ...

    African Journals Online (AJOL)

    Purpose: To develop and characterize solid lipid nanoparticle (SLN) systems containing dextran sulfate or sodium ... SLNs. Drug release from SLNs is also dependent on the polymer type. ..... nanoparticles for parenteral drug delivery. Adv.

  11. Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development.

    Science.gov (United States)

    Li, Min; Sander, Sanna; Duan, John; Rosencrance, Susan; Miksinski, Sarah Pope; Yu, Lawrence; Seo, Paul; Rege, Bhagwant

    2016-11-01

    This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.

  12. Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin.

    Science.gov (United States)

    Ji, Hongyu; Tang, Jingling; Li, Mengting; Ren, Jinmei; Zheng, Nannan; Wu, Linhua

    2016-01-01

    The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin. The formulation was optimized by Plackett-Burman screening design and Box-Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin. The optimized formulations showed an average size of 135.3 ± 1.5 nm with a zeta potential value of -24.7 ± 2.1 mV and 91.09% ± 1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, Tmax and t(1/2) of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p curcumin for SLNs was significantly improved (p curcumin solution. Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively.

  13. 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.

  14. Resolving Radiological Classification and Release Issues for Many DOE Solid Wastes and Salvageable Materials

    Energy Technology Data Exchange (ETDEWEB)

    Hochel, R.C.

    1999-11-19

    The cost effective radiological classification and disposal of solid materials with potential volume contamination, in accordance with applicable U.S. Department of Energy (DOE) Orders, suffers from an inability to unambiguously distinguish among transuranic waste, low-level waste, and unconditional-release materials in a generic way allowing in-situ measurement and verification. Depending on a material''s classification, disposal costs can vary by a hundred-fold. With these large costs at risk, the issues involved in making defensible decisions are ripe for closer scrutiny. In many cases, key issues can be easily resolved by a combination of process information, some simple measurements, and calculational predictions from a computer model for radiation shielding. The proper classification and disposal of many solid wastes requires a measurement regime that is able to show compliance with a variety of institutional and regulatory contamination limits. Ultimate responsibility for this, of course, rests with radiological control or health physics organization of the individual site, but there are many measurements which can be performed by operations and generation organizations to simplify the process and virtually guarantee acceptance. Although this is not possible for all potential solid wastes, there are many that do lend themselves to such measures, particularly some of large volumes and realizable cost savings. Mostly what is needed for this to happen are a few guiding rules, measurement procedures, and cross checks for potential pitfalls. Several examples are presented here and discussed that demonstrate the possibilities, including one which was successfully applied to bulk contamination.

  15. Lipidized prolactin-releasing peptide analogs: A new tool for obesity treatment

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Pražienková, Veronika; Zemenová, Jana; Popelová, Andrea; Blechová, Miroslava; Mikulášková, Barbora; Holubová, Martina; Železná, Blanka; Kuneš, Jaroslav

    2016-01-01

    Roč. 22, Suppl S2 (2016), S179-S180 ISSN 1075-2617. [European Peptide Symposium /34./ and International Peptide Symposium /8./. 04.09.2016-09.09.2016, Leipzig] R&D Projects: GA TA ČR(CZ) TE01020028; GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * food intake * obesity Subject RIV: CE - Biochemistry

  16. Development of curcumin-loaded solid lipid nanoparticles utilizing glyceryl monostearate as single lipid using QbD approach: Characterization and Evaluation of anticancer activity against human breast cancer cell line.

    Science.gov (United States)

    Bhatt, Himanshu; Rompicharla, Sri Vishnu Kiran; Komanduri, Neeraja; Shah, Aashma; Paradkar, Sateja; Ghosh, Balaram; Biswas, Swati

    2018-05-03

    Solid lipid nanoparticles (SLNs) represent an affordable, easily scalable, stable and biocompatible drug delivery system with a high drug to lipid ratio which also improves solubility of poorly soluble drugs. SLNs were developed by using glyceryl monostearate as the single lipid in presence of surfactant Poloxamer 188 and evaluated the efficiency of the SLNs to load the therapeutic cargo, curcumin (CUR). The nano-formulation was optimized by Quality by Design approach to understand the effect of various process parameters on various quality attributes, including drug loadability, particle size and polydispersity. The nanoparticles were characterized using Differential scanning calorimetry (DSC), Fourier Transform Infra-red Spectroscopy (FT-IR) and X-Ray Diffraction (XRD) analysis. These novel SLNs were evaluated for in-vitro anticancer activity using breast adenocarcinoma cells (MDA-MB-231). The optimized formulation had particle size of 226.802±3.92 nm with low polydispersity index of 0.244±0.018. The % encapsulation of CUR into SLNs was found to be 67.88±2.08 %. DSC, FT-IR and XRD confirmed that the CUR was encapsulated stably into the lipid matrix, thereby improving the solubility of the drug. CUR-SLN showed sustained drug release in comparison to the free CUR solution. CUR-SLNs exhibited higher cellular uptake in human breast adenocarcinoma cells compared to free CUR at both 1 and 4 h time points. CUR-SLNs demonstrated decreased cell viability (43.97±1.53%) compared to free CUR (59.33±0.95%) at a concentration of 50 μg/mL after 24 h treatment. Further, treatment of MDA-MB-231 cells with CUR-SLNs for 24 h induced significantly higher apoptosis (37.28±5.3%) in cells compared to the free CUR (21.06±0.97%). The results provide strong rationale for further exploration of the newly developed CUR-SLN to be utilized as a potent chemotherapeutic agent in cancer therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Flow-through lipid nanotube arrays for structure-function studies of membrane proteins by solid-state NMR spectroscopy.

    Science.gov (United States)

    Chekmenev, Eduard Y; Gor'kov, Peter L; Cross, Timothy A; Alaouie, Ali M; Smirnov, Alex I

    2006-10-15

    A novel method for studying membrane proteins in a native lipid bilayer environment by solid-state NMR spectroscopy is described and tested. Anodic aluminum oxide (AAO) substrates with flow-through 175 nm wide and 60-mum-long nanopores were employed to form macroscopically aligned peptide-containing lipid bilayers that are fluid and highly hydrated. We demonstrate that the surfaces of both leaflets of such bilayers are fully accessible to aqueous solutes. Thus, high hydration levels as well as pH and desirable ion and/or drug concentrations could be easily maintained and modified as desired in a series of experiments with the same sample. The method allows for membrane protein NMR experiments in a broad pH range that could be extended to as low as 1 and as high as 12 units for a period of up to a few hours and temperatures as high as 70 degrees C without losing the lipid alignment or bilayers from the nanopores. We demonstrate the utility of this method by a solid-state 19.6 T (17)O NMR study of reversible binding effects of mono- and divalent ions on the chemical shift properties of the Leu(10) carbonyl oxygen of transmembrane pore-forming peptide gramicidin A (gA). We further compare the (17)O shifts induced by binding metal ions to the binding of protons in the pH range from 1 to 12 and find a significant difference. This unexpected result points to a difference in mechanisms for ion and proton conduction by the gA pore. We believe that a large number of solid-state NMR-based studies, including structure-function, drug screening, proton exchange, pH, and other titration experiments, will benefit significantly from the method described here.

  18. Evaluation of in-vitro cytotoxicity and cellular uptake efficiency of zidovudine-loaded solid lipid nanoparticles modified with Aloe Vera in glioma cells.

    Science.gov (United States)

    K S, Joshy; Sharma, Chandra P; Kalarikkal, Nandakumar; Sandeep, K; Thomas, Sabu; Pothen, Laly A

    2016-09-01

    Zidovudine loaded solid lipid nanoparticles of stearic acid modified with Aloe Vera (AV) have been prepared via simple emulsion solvent evaporation method which showed excellent stability at room temperature and refrigerated condition. The nanoparticles were examined by Fourier transform infrared spectroscopy (FT-IR), which revealed the overlap of the AV absorption peak with the absorption peak of modified stearic acid nanoparticles. The inclusion of AV to stearic acid decreased the crystallinity and improved the hydrophilicity of lipid nanoparticles and thereby improved the drug loading efficacy of lipid nanoparticles. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) imaging revealed that, the average particle size of unmodified (bare) nanoparticles was 45.66±12.22nm and modified solid lipid nanoparticles showed an average size of 265.61±80.44nm. Solid lipid nanoparticles with well-defined morphology were tested in vitro for their possible application in drug delivery. Cell culture studies using C6 glioma cells on the nanoparticles showed enhanced growth and proliferation of cells without exhibiting any toxicity. In addition, normal cell morphology and improved uptake were observed by fluorescence microscopy images of rhodamine labeled modified solid lipid nanoparticles compared with unmodified nanoparticles. The cellular uptake study suggested that these nanoparticles could be a promising drug delivery system to enhance the uptake of antiviral drug by brain cells and it could be a suitable drug carrier system for the treatment of HIV. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Novel dual-reverse thermosensitive solid lipid nanoparticle-loaded hydrogel for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect.

    Science.gov (United States)

    Din, Fakhar Ud; Mustapha, Omer; Kim, Dong Wuk; Rashid, Rehmana; Park, Jong Hyuck; Choi, Ju Yeon; Ku, Sae Kwang; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

    2015-08-01

    The purpose of this study was to develop novel solid lipid nanoparticle (SLN)-loaded dual-reverse thermosensitive hydrogel (DRTH) for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect. The flurbiprofen-loaded SLNs were prepared by hot homogenisation technique, after optimising the amounts of lipid mixture (tricaprin and triethanolamine in 8:2 weight ratio), drug and surfactant. The flurbiprofen-loaded thermosensitive SLN composed of drug, lipid mixture and surfactant at a weight ratio of 10/15/1.3 was a solid at room temperature, and changed to liquid form at physiological temperature due to its melting point of about 32°C. This SLN gave the mean particle size of about 190nm and entrapment efficiency of around 90%. The DRTHs were prepared by adding this flurbiprofen-loaded thermosensitive SLN in various poloxamer solutions. Their rheological characterisation, release and stability were investigated while a morphological and pharmacokinetic study was performed after its rectal administration to rats compared with the drug and hydrogel. Poloxamer 188 and SLN decreased the gelation temperature and gelation time, but increased the viscosity at 25°C, gel strength and mucoadhesive force of DRTHs. In particular, the DRTH composed of [SLN/P 407/P 188 (10%/15%/25%)] with the gelation temperature of about 35°C existed as liquid at room temperature, but gelled at 30-36°C, leading to opposite reversible property of SLN. Thus, it was easy to administer rectally, and it gelled rapidly inside the body. This DRTH gave a significantly increased dissolution rate of the drug as compared to the flurbiprofen, but significantly retarded as compared to the hydrogel, including the initial dissolution rate. Moreover, this DRTH gave significantly higher plasma concentration and 7.5-fold AUC values compared to the drug, and lower initial plasma concentration and Cmax value compared to the hydrogel due to reduced initial burst effect. No

  20. Solubility enhancement of benfotiamine, a lipid derivative of thiamine by solid dispersion technique.

    Science.gov (United States)

    Patel, S M; Patel, R P; Prajapati, B G

    2012-03-01

    The present study was aimed to increase the solubility of the poorly water soluble drug benfotiamine using hydrophilic polymers (PVP K-30 and HPMC E4). Solid dispersions were prepared by kneading method. Phase solubility study, in-vitro dissolution of pure drug, physical mixtures and solid dispersions were carried out. PVP and HPMC were found to be effective in increasing the dissolution of Benfotiamine in solid dispersions when compared to pure drug. FT-IR, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and solid dispersion. To conclude that, the prepared solid dispersion of PVP-30 may to effectively used for the enhancement of solubility of poorly water soluble drugs such as benfotiamine.

  1. Solubility enhancement of benfotiamine, a lipid derivative of thiamine by solid dispersion technique

    Directory of Open Access Journals (Sweden)

    S M Patel

    2012-01-01

    Full Text Available The present study was aimed to increase the solubility of the poorly water soluble drug benfotiamine using hydrophilic polymers (PVP K-30 and HPMC E4. Solid dispersions were prepared by kneading method. Phase solubility study, in-vitro dissolution of pure drug, physical mixtures and solid dispersions were carried out. PVP and HPMC were found to be effective in increasing the dissolution of Benfotiamine in solid dispersions when compared to pure drug. FT-IR, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and solid dispersion. To conclude that, the prepared solid dispersion of PVP-30 may to effectively used for the enhancement of solubility of poorly water soluble drugs such as benfotiamine.

  2. Characterization and evaluation of sensory acceptability of ice creams incorporated with beta-carotene encapsulated in solid lipid microparticles

    Directory of Open Access Journals (Sweden)

    Juliana Gobbi de LIMA

    Full Text Available Abstract The feasibility of incorporating beta-carotene-loaded solid lipid microparticles (BCSLM into vanilla ice creams was investigated, through the physico-chemical characterization and evaluation of sensory acceptability of the products products. The BCSLM were produced with palm stearin as the lipid phase, hydrolyzed soy protein isolate as the surfactant, and xanthan gum as the thickener. The results showed similar values of proximate composition, total soluble solids, pH, and overrun for all formulations. On the other hand, colorimetric evaluations showed that the ice cream produced with partial substitution of artificial additives by BCSLM containing alpha-tocopherol presented a more intense color, while in the product with non-encapsulated beta-carotene, a fast degradation of carotenoid was confirmed, highlighting the importance of the encapsulation techniques. The results of the sensorial analysis of the products were highly satisfactory and showed that the panelists preferred the ice creams produced with BCSLM containing alpha-tocopherol and with partial substitution of artificial additives by BCSLM containing alpha-tocopherol, confirming the feasibility of incorporating BCSLM into ice creams to reduce the application of artificial dyes to the product.

  3. Skin penetration and photoprotection of topical formulations containing benzophenone-3 solid lipid microparticles prepared by the solvent-free spray-congealing technique.

    Science.gov (United States)

    Martins, Rodrigo Molina; Siqueira, Silvia; Fonseca, Maria José Vieira; Freitas, Luis Alexandre Pedro

    2014-01-01

    Solid-lipid microparticles loaded with high amounts of the sunscreen UV filter benzophenone-3 were prepared by spray congealing with the objective of decreasing its skin penetration and evaluate whether the sunscreen's photoprotection were impaired by the microencapsulation process. The microparticles were produced using the natural lipids carnauba wax or bees wax and three different concentrations of benzophenone-3 (30, 50 and 70%) using spray congealing technique. The microparticles presented properties suitable for topical application, such as spherical morphology, high encapsulation efficiency (95.53-102.2%), average particle sizes between 28.5 and 60.0 µm with polydispersivities from 1.2 to 2.5. In studies of in vitro skin penetration and preliminary stability, formulations of gel cream containing carnauba wax solid lipid microparticles and 70% benzophenone-3 when compared to the formulation added of bees wax solid-lipid microparticles containing 70% benzophenone-3, was stable considering the several parameters evaluated and were able to decrease the penetration of the UV filter into pig skin. Moreover, the formulations containing solid lipid microparticles with 70% benzophenone-3 increased the photoprotective capacity of benzophenone-3 under UV irradiation. The results show that spray-congealed microparticles are interesting solid forms to decrease the penetration solar filters in the skin without compromising their photoprotection.

  4. The Effect in Vitro of Ionizing Irradiation and Small Rises in Temperature on the Uptake and Release of Labelled Lipids by the Human Erythrocyte Membrane

    DEFF Research Database (Denmark)

    Hansen, Heinz Johs. Max; Karle, H.; Stender, S.

    1978-01-01

    1. The effect of X-irradiation (50 000 rad) and an increase in temperature from 37 to 42° C on the synthesis, uptake and release of labelled lipids by erythrocytes was studied in plasma incubations in vitro. 2. Both irradiation and a rise in temperature resulted in an enhanced synthesis of [32P]phosphatidic...

  5. Disintegration mediated controlled release supersaturating solid dispersion formulation of an insoluble drug: design, development, optimization, and in vitro evaluation.

    Science.gov (United States)

    Verma, Sanjay; Rudraraju, Varma S

    2015-02-01

    The objective of this study was to develop a solid dispersion based controlled release system for drug substances that are poorly soluble in water. A wax-based disintegration mediated controlled release system was designed based on the fact that an amorphous drug can crystallize out from hydrophilic matrices. For this study, cilostazol (CIL) was selected as the model drug, as it exhibits poor aqueous solubility. An amorphous solid dispersion was prepared to assist the drug to attain a supersaturated state. Povidone was used as carrier for solid dispersion (spray drying technique), hydrogenated vegetable oil (HVO) as wax matrix former, and sodium carboxymethyl cellulose (NaCMC) as a disintegrant. The extreme vertices mixture design (EVMD) was applied to optimize the designed and developed composition. The optimized formulation provided a dissolution pattern which was equivalent to the predicted curve, ascertaining that the optimal formulation could be accomplished with EVMD. The release profile of CIL was described by the Higuchi's model better than zero-order, first-order, and Hixson-Crowell's model, which indicated that the supersaturation state of CIL dominated to allow drug release by diffusion rather than disintegration regulated release as is generally observed by Hixson-Crowell's model. The optimized composition was evaluated for disintegration, dissolution, XRD, and stability studies. It was found that the amorphous state as well as the dissolution profile of CIL was maintained under the accelerated conditions of 40°C/75% RH for 6 months.

  6. Steric effects in release of amides from linkers in solid-phase synthesis. Molecular mechanics modeling of key step in peptide and combinatorial chemistry

    DEFF Research Database (Denmark)

    Norrby, Per-Ola; Jensen, Knud Jørgen

    2006-01-01

    Acidolytic release of an amide from a solid support by C-N bond cleavage is all ubiquitous and crucial step in many solid-phase syntheses. We have used molecular modeling of a pseudo-equilibrium to explore substituent and steric effects in the release of peptides. The high acid-lability of the ba......Acidolytic release of an amide from a solid support by C-N bond cleavage is all ubiquitous and crucial step in many solid-phase syntheses. We have used molecular modeling of a pseudo-equilibrium to explore substituent and steric effects in the release of peptides. The high acid......-lability of the backbone amide linkage (BAL), which releases sec. amides, compared to C-terminal amide anchoring, which releases primary amides, was rationalized by steric relief upon cleavage. Thus, the relative stability of the carbenium ion formed from the linker in the acidolytic release is an insufficient measure...

  7. Biowaiver monograph for immediate-release solid oral dosage forms: bisoprolol fumarate.

    Science.gov (United States)

    Charoo, Naseem A; Shamsher, Areeg A A; Lian, Lai Y; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

    2014-02-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing bisoprolol as the sole active pharmaceutical ingredient (API) are reviewed. Bisoprolol is classified as a Class I API according to the current Biopharmaceutics Classification System (BCS). In addition to the BCS class, its therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability problems are taken into consideration. Qualitative compositions of IR tablet dosage forms of bisoprolol with a marketing authorization (MA) in ICH (International Conference on Harmonisation) countries are tabulated. It was inferred that these tablets had been demonstrated to be bioequivalent to the innovator product. No reports of failure to meet BE standards have been made in the open literature. On the basis of all these pieces of evidence, a biowaiver can currently be recommended for bisoprolol fumarate IR dosage forms if (1) the test product contains only excipients that are well known, and used in normal amounts, for example, those tabulated for products with MA in ICH countries and (2) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  8. Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms.

    Science.gov (United States)

    Hermans, Andre; Abend, Andreas M; Kesisoglou, Filippos; Flanagan, Talia; Cohen, Michael J; Diaz, Dorys A; Mao, Y; Zhang, Limin; Webster, Gregory K; Lin, Yiqing; Hahn, David A; Coutant, Carrie A; Grady, Haiyan

    2017-11-01

    This manuscript represents the perspective of the Dissolution Analytical Working Group of the IQ Consortium. The intent of this manuscript is to highlight the challenges of, and to provide a recommendation on, the development of clinically relevant dissolution specifications (CRS) for immediate release (IR) solid oral dosage forms. A roadmap toward the development of CRS for IR products containing active ingredients with a non-narrow therapeutic window is discussed, within the context of mechanistic dissolution understanding, supported by in-human pharmacokinetic (PK) data. Two case studies present potential outcomes of following the CRS roadmap and setting dissolution specifications. These cases reveal some benefits and challenges of pursuing CRS with additional PK data, in light of current regulatory positions, including that of the US Food and Drug Administration (FDA), who generally favor this approach, but with the understanding that both industry and regulatory agency perspectives are still evolving in this relatively new field. The CRS roadmap discussed in this manuscript also describes a way to develop clinically relevant dissolution specifications based primarily on dissolution data for batches used in pivotal clinical studies, acknowledging that not all IR product development efforts need to be supported by additional PK studies, albeit with the associated risk of potentially unnecessarily tight manufacturing controls. Recommendations are provided on what stages during the life cycle investment into in vivo studies may be valuable. Finally, the opportunities for CRS within the context of post-approval changes, Modeling and Simulation (M&S), and the application of biowaivers, are briefly discussed.

  9. Investigation of radionuclide release from Solid Waste Disposal Area 3, Oak Ridge National Laboratory

    International Nuclear Information System (INIS)

    Stueber, A.M.; Webster, D.A.; Munro, I.L.; Farrow, N.D.; Scott, T.G.

    1981-08-01

    Radionuclide release from Solid Waste Disposal Area (SWDA) 3 has been studied through the analysis of surface and ground waters from the local drainage areas. SWDA 3 is located in the Northwest Tributary drainage basin, a part of the White Oak Creek drainage; 90 Sr is the only radionuclide being discharged in solution in the main stream. Water-level measurements in wells around SWDA 3 suggest the presence of a ground-water divide beneath the southwestern end of the disposal area. Ground water below this area may be moving southwestward toward the Raccoon Creek drainage system. Strontium-90 activity has been detected in this watershed, discharging from a seep adjacent to a Raccoon Creek tributary stream about 640 m southwest of SWDA 3. It appears that 90 Sr is moving through ground-water flow to the northeast and to the southwest of SWDA 3 and that this direction of movement is related to bedrock structure. The trend of a line connecting the two seeps passes through the disposal area and is parallel to bedrock strike. Information from core-hole logs and televiewer logs suggests that 90 Sr in ground water may be moving through solution channels near the contact between units F and G of the Chickamauga Limestone. The apparent extent of migration of 90 Sr in bedrock has implications regarding potential underground radionuclide movement in Melton Valley

  10. Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Enalapril.

    Science.gov (United States)

    Verbeeck, Roger K; Kanfer, Isadore; Löbenberg, Raimar; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Langguth, Peter; Polli, James E; Parr, Alan; Shah, Vinod P; Mehta, Mehul; Dressman, Jennifer B

    2017-08-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence testing for the marketing authorization of immediate-release, solid oral dosage forms containing enalapril maleate are reviewed. Enalapril, a prodrug, is hydrolyzed by carboxylesterases to the active angiotensin-converting enzyme inhibitor enalaprilat. Enalapril as the maleate salt is shown to be highly soluble, but only 60%-70% of an orally administered dose of enalapril is absorbed from the gastrointestinal tract into the enterocytes. Consequently, enalapril maleate is a Biopharmaceutics Classification System class III substance. Because in situ conversion of the maleate salt to the sodium salt is sometimes used in production of the finished drug product, not every enalapril maleate-labeled finished product actually contains the maleate salt. Enalapril is not considered to have a narrow therapeutic index. With this background, a biowaiver-based approval procedure for new generic products or after major revisions to existing products is deemed acceptable, provided the in vitro dissolution of both test and reference preparation is very rapid (at least 85% within 15 min at pH 1.2, 4.5, and 6.8). Additionally, the test and reference product must contain the identical active drug ingredient. Copyright © 2017 American Pharmacists Association®. All rights reserved.

  11. pH-Responsive therapeutic solid lipid nanoparticles for reducing P-glycoprotein-mediated drug efflux of multidrug resistant cancer cells

    Directory of Open Access Journals (Sweden)

    Chen HH

    2015-08-01

    Full Text Available Hsin-Hung Chen,1 Wen-Chia Huang,2 Wen-Hsuan Chiang,2 Te-I Liu,2 Ming-Yin Shen,2,3 Yuan-Hung Hsu,4 Sung-Chyr Lin,1 Hsin-Cheng Chiu2 1Department of Chemical Engineering, National Chung Hsing University, Taichung, 2Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 3Department of Surgery, National Taiwan University Hospital-Hsinchu Branch, 4Pharmaceutical Optimization Technology Division, Biomedical Technology and Device Research Laboratory, Industrial Technology Research Institute, Hsinchu, Taiwan Abstract: In this study, a novel pH-responsive cholesterol-PEG adduct-coated solid lipid nanoparticles (C-PEG-SLNs carrying doxorubicin (DOX capable of overcoming multidrug resistance (MDR breast cancer cells is presented. The DOX-loaded SLNs have a mean hydrodynamic diameter of ~100 nm and a low polydispersity index (under 0.20 with a high drug-loading efficiency ranging from 80.8% to 90.6%. The in vitro drug release profiles show that the DOX-loaded SLNs exhibit a pH-controlled drug release behavior with the maximum and minimum unloading percentages of 63.4% at pH 4.7 and 25.2% at pH 7.4, respectively. The DOX-loaded C-PEG-SLNs displayed a superior ability in inhibiting the proliferation of MCF-7/MDR cells. At a DOX concentration of 80 µM, the cell viabilities treated with C-PEG-SLNs were approximately one-third of the group treated with free DOX. The inhibition activity of C-PEG-SLNs could be attributed to the transport of C-PEG to cell membrane, leading to the change of the composition of the cell membrane and thus the inhibition of permeability glycoprotein activity. This hypothesis is supported by the confocal images showing the accumulation of DOX in the nuclei of cancer cells and the localization of C-PEG on the cell membranes. The results of in vivo study further demonstrated that the DOX delivered by the SLNs accumulates predominantly in tumor via enhanced permeability and retention effect, the

  12. PENGEMBANGAN SISTEM NANOSTRUCTURED LIPID CARRIERS (NLC MELOXICAM DENGAN LIPID MONOSTEARIN DAN MIGLYOL 808 MENGGUNAKAN METODE EMULSIFIKASI

    Directory of Open Access Journals (Sweden)

    Rahmi Annisa

    2016-06-01

    Full Text Available The aim this study was to determine the effect of Monostearin and Miglyol 808 lipid ratio in NLC system formulation resulting in physicochemical characteristics, release rate, and penetration rate. The NLC making was done by using emulsification method. In the formulation of NLC meloxicam, 3 different lipid ratios were used, including ratios of 6:4, 7:3, 8:2.  Meloxicam served as active ingredient, monostearin served as solid lipid, miglyol 808 served as a liquid lipid, and tween 80 was surfactant. NLC meloxicam physicochemical characteristics include tests of organoleptic, pH, viscosity, particle size, particle morphology and entrapment efficiency. NLC meloxicam belongs to semisolid preparations with pH value range of 5,72-5,87. Increasing viscosity of NLC system are cause by increase of solid lipid. The measurement results of particle size of three different lipid formulas indicated that the lipid particle size was 80%. The determination of release rate (flux and penetration rate (flux was conducted by using Franz diffusion cells with a cellophane membrane for the release and Wistar rat’s skin membrane for the penetration. The release rate values of three NLC meloxicam formulas showed p value (sig 0,005, while the penetration rate obtained p value (sig 0,091. Keywords: NLC, meloxicam, physicochemical characterization, release rate and penetration rate

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

    Science.gov (United States)

    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

  14. Multifunctional Cationic Lipid-Based Nanoparticles Facilitate Endosomal Escape and Reduction-Triggered Cytosolic siRNA Release

    Science.gov (United States)

    Gujrati, Maneesh; Malamas, Anthony; Shin, Tesia; Jin, Erlei; Sun, Lulu; Lu, Zheng-Rong

    2015-01-01

    Small interfering RNA (siRNA) has garnered much attention in recent years as a promising avenue for cancer gene therapy due to its ability to silence disease-related genes. Effective gene silencing is contingent upon the delivery of siRNA into the cytosol of target cells and requires the implementation of delivery systems possessing multiple functionalities to overcome delivery barriers. The present work explores the multifunctional properties and biological activity of a recently developed cationic lipid carrier, (1-aminoethyl)iminobis[N-(oleicylcysteinyl-1-amino-ethyl)propionamide]) (ECO). The physicochemical properties and biological activity of ECO/siRNA nanoparticles were assessed over a range of N/P ratios to optimize the formulation. Potent and sustained luciferase silencing in a U87 glioblastoma cell line was observed, even in the presence of serum proteins. ECO/siRNA nanoparticles exhibited pH-dependent membrane disruption at pH levels corresponding to various stages of the intracellular trafficking pathway. It was found that disulfide linkages created during nanoparticle formation enhanced the protection of siRNA from degradation and facilitated site-specific siRNA release in the cytosol by glutathione-mediated reduction. Confocal microscopy confirmed that ECO/siRNA nanoparticles readily escaped from late endosomes prior to cytosolic release of the siRNA cargo. These results demonstrate that the rationally designed multifunctionality of ECO/siRNA nanoparticles is critical for intracellular siRNA delivery and the continuing development of safe and effective delivery systems. PMID:25020033

  15. Kinetics of milk lipid droplet transport, growth, and secretion revealed by intravital imaging: lipid droplet release is intermittently stimulated by oxytocin | Center for Cancer Research

    Science.gov (United States)

    Description of the cover: The micrograph shows lipid droplets (red) accumulating at the apical surface of secretory cells (green) between oxytocin-induced contractions in a transgenic mouse line that expresses green fluorescent protein in the cytoplasm of most cells.

  16. Biowaiver monograph for immediate-release solid oral dosage forms: fluconazole.

    Science.gov (United States)

    Charoo, Naseem; Cristofoletti, Rodrigo; Graham, Alexandra; Lartey, Paul; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

    2014-12-01

    Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence (BE) testing requirements for the approval of immediate release (IR) solid oral dosage forms containing fluconazole as the only active pharmaceutical ingredient (API) are reviewed. The decision is based on solubility, dissolution, permeability, therapeutic index, pharmacokinetic parameters, pharmacodynamic properties, and other relevant data. BE/bioavailability (BA) problems and drug-excipients interaction data were also reviewed and taken into consideration. According to the biopharmaceutics classification system (BCS), fluconazole in polymorphic forms II and III is a BCS class I drug and has a wide therapeutic index. BE of test formulations from many different manufacturers containing different excipients confirmed that the risk of bioinequivalence because of formulation and manufacturing factors is low. It was inferred that risk can be further reduced if in vitro studies are performed according to biowaiver guidelines. Thus, it is concluded that a biowaiver can be recommended for fluconazole IR dosage forms if (a) fluconazole is present as polymorphic form II or III or any other form/mixture showing high solubility, (b) the selection of excipients be limited to those found in IR drug products approved in International Conference on Harmonisation (ICH) countries for the same dosage form and used in their usual amounts, and (c) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving throughout the shelf life with similar dissolution profiles at pH 1.2, 4.5, and 6.8. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  17. Solid state NMR investigations and MD simulations of triblock copolymers in lipid bilayers

    Czech Academy of Sciences Publication Activity Database

    Baerenwald, R.; Ferreira, T. M.; Ollila, Samuli; Saalwaechter, K.

    2017-01-01

    Roč. 46, Suppl 1 (2017), S117 ISSN 0175-7571. [IUPAB congress /19./ and EBSA congress /11./. 16.07.2017-20.07.2017, Edinburgh] Institutional support: RVO:61388963 Keywords : solid state NMR * molecular dynamic simulations Subject RIV: BO - Biophysics

  18. Understanding the mechanism of protamine in solid lipid nanoparticle-based lipofection: the importance of the entry pathway.

    Science.gov (United States)

    Delgado, Diego; del Pozo-Rodríguez, Ana; Solinís, Maria Ángeles; Rodríguez-Gascón, Alicia

    2011-11-01

    The aim of our study was to evaluate the effect of protamine on the transfection capacity of solid lipid nanoparticles (SLNs) by correlating it to the internalization mechanisms and intracellular trafficking of the vectors. Vectors were prepared with SLN, DNA, and protamine. ARPE-19 and HEK-293 cells were used for the evaluation of the formulations. Protamine induced a 6-fold increase in the transfection of SLNs in retinal cells due to the presence of nuclear localization signals (NLS), its protection capacity, and a shift in the internalization mechanism from caveolae/raft-mediated to clathrin-mediated endocytosis. However, protamine produced an almost complete inhibition of transfection in HEK-293 cells. In spite of the high DNA condensation capacity of protamine and its content in NLS, this does not always lead to an improvement in cell transfection since it may impair some of the limiting steps of the transfection processes. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. 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

    that fluorescently labelled SLN were detected in the brain after i.v. administration. This study indicates that the camptothecin-loaded SLN are a promising drug brain delivery system worth to explore further for brain tumour therapy. (C) 2012 Elsevier B. V. All rights reserved.......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...

  20. Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients.

    Science.gov (United States)

    Tanzi, Maria G; Undre, Nasrullah; Keirns, James; Fitzsimmons, William E; Brown, Malcolm; First, M Roy

    2016-08-01

    Prolonged-release tacrolimus was developed as a once-daily formulation with ethylcellulose as the excipient, resulting in slower release and reduction in peak concentration (Cmax ) for a given dose compared with immediate-release tacrolimus, which is administered twice daily. This manuscript reviews pharmacokinetic information on prolonged-release tacrolimus in healthy subjects, in transplant recipients converted from immediate-release tacrolimus, and in de novo kidney and liver transplant recipients. As with the immediate-release formulation, prolonged-release tacrolimus shows a strong correlation between trough concentration (Cmin ) and area under the 24-hour time-concentration curve (AUC24 ), indicating that trough whole blood concentrations provide an accurate measure of drug exposure. We present the pharmacokinetic similarities and differences between the two formulations, so that prescribing physicians will have a better understanding of therapeutic drug monitoring in patients receiving prolonged-release tacrolimus. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Continuous production of fenofibrate solid lipid nanoparticles by hot-melt extrusion technology: a systematic study based on a quality by design approach.

    Science.gov (United States)

    Patil, Hemlata; Feng, Xin; Ye, Xingyou; Majumdar, Soumyajit; Repka, Michael A

    2015-01-01

    This contribution describes a continuous process for the production of solid lipid nanoparticles (SLN) as drug-carrier systems via hot-melt extrusion (HME). Presently, HME technology has not been used for the manufacturing of SLN. Generally, SLN are prepared as a batch process, which is time consuming and may result in variability of end-product quality attributes. In this study, using Quality by Design (QbD) principles, we were able to achieve continuous production of SLN by combining two processes: HME technology for melt-emulsification and high-pressure homogenization (HPH) for size reduction. Fenofibrate (FBT), a poorly water-soluble model drug, was incorporated into SLN using HME-HPH methods. The developed novel platform demonstrated better process control and size reduction compared to the conventional process of hot homogenization (batch process). Varying the process parameters enabled the production of SLN below 200 nm. The dissolution profile of the FBT SLN prepared by the novel HME-HPH method was faster than that of the crude FBT and a micronized marketed FBT formulation. At the end of a 5-h in vitro dissolution study, a SLN formulation released 92-93% of drug, whereas drug release was approximately 65 and 45% for the marketed micronized formulation and crude drug, respectively. Also, pharmacokinetic study results demonstrated a statistical increase in Cmax, Tmax, and AUC0-24 h in the rate of drug absorption from SLN formulations as compared to the crude drug and marketed micronized formulation. In summary, the present study demonstrated the potential use of hot-melt extrusion technology for continuous and large-scale production of SLN.

  2. PENGEMBANGAN SISTEM NANOSTRUCTURED LIPID CARRIERS (NLC) MELOXICAM DENGAN LIPID MONOSTEARIN DAN MIGLYOL 808 MENGGUNAKAN METODE EMULSIFIKASI

    OpenAIRE

    Rahmi Annisa; Esti Hendradi; Dewi Melani

    2016-01-01

    The aim this study was to determine the effect of Monostearin and Miglyol 808 lipid ratio in NLC system formulation resulting in physicochemical characteristics, release rate, and penetration rate. The NLC making was done by using emulsification method. In the formulation of NLC meloxicam, 3 different lipid ratios were used, including ratios of 6:4, 7:3, 8:2.  Meloxicam served as active ingredient, monostearin served as solid lipid, miglyol 808 served as a liquid lipid, and tween 80 was surfa...

  3. Polar Quassinoids in Standardized Eurycoma longifolia Extract Formulated into a Lipid-Based Solid Dispersion to Improve Rat Sperm Count.

    Science.gov (United States)

    Ma, Hai-Qiu; Ebrahimi, Forough; Low, Bin-Seng; Khan, Nurzalina Abdul Karim; Chan, Kit-Lam

    2017-12-01

    Eurycoma longifolia Jack is popularly sought in Southeast Asian countries for traditional remedies to improve sexual performance and fertility. 13α(21)-Epoxyeurycomanone and eurycomanone, two major quassinoids in a root extract (TAF2) were reported to improve rat spermatogenesis and fertility. Unfortunately, these quassinoids possess low bioavailability because of high aqueous solubility and low lipid membrane permeability. Often, other possible barriers may be P-glycoprotein (P-gp) efflux in the gut and presystemic hepatic metabolism. The present study attempted to solve these problems by formulating a lipid-based solid dispersion (TAF2-SD) of optimized mixture of TAF2 and emulsifiers, which was then orally administered to rats prior to sperm count analysis. The TAF2-SD-treated rats showed significantly twofold (p < 0.001) and fourfold (p < 0.001) higher sperm count than did TAF2-treated and vehicle-treated (control) rats, respectively. The study also demonstrated no significant in vitro ileal absorption changes of the quassinoids by P-gp efflux inhibitors and concentration change or secondary metabolite formation upon in vitro incubation with rat liver homogenates, suggesting that P-gp-mediated efflux and presystemic metabolism were not limiting their bioavailability. Further study on orally TAF2-treated rats confirmed that the area under the curve and bioavailability curve of each quassinoid in the absence and presence of ketoconazole were unchanged. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Luteolin-loaded solid lipid nanoparticles synthesis, characterization, & improvement of bioavailability, pharmacokinetics in vitro and vivo studies

    Science.gov (United States)

    Dang, Hao; Meng, Murtaza Hasan Weiwei; Zhao, Haiwei; Iqbal, Javed; Dai, Rongji; Deng, Yulin; Lv, Fang

    2014-04-01

    Luteolin (LU, 5,7,3',4'-tetrahydroxyflavone) most active compound in Chinese herbal flavones has been acting as a antimicrobial, anti-inflammatory, anti-cancer, and antimutagen. However, its poor bioavailability, hydrophobicity, and pharmacokinetics restrict clinical application. Here in this study, LU-loaded solid lipid nanoparticles have been prepared by hot-microemulsion ultrasonic technique to improve the bioavailability & pharmacokinetics of compound. LU-loaded solid lipid nanoparticle size was confirmed by particle size analyzer with range from 47 to 118 nm, having zepta potential -9.2 mV and polydisperse index 0.247, respectively. Round-shaped SLNPs were obtained by using transmission electron microscope, and encapsulation efficiency 74.80 % was calculated by using HPLC. Both in vitro and vivo studies, LC-MS/MS technique was used for quantification of Luteolin in rat. The T max value of drug with LU-SLNs after the administration was Ten times shorter than pure Luteolin suspension administration. C max value of drug after the administration of LU-SLNs was five times higher than obtained with native drug suspension. Luteolin with SLNs has increased the half-life approximately up to 2 h. Distribution and clearance of drug with SLNs were significantly decreased by 2.16-10.57 fold, respectively. In the end, the relative bioavailability of SLNs has improved about 4.89 compared to Luteolin with SLNs. From this study, it can be concluded that LU-SLNs have not only great potential for improving solubility but also increased the drug concentration in plasma. Furthermore, use of LC-MS/MS for quantification of LU-SLNs in rat plasma is reliable and of therapeutic usefulness, especially for neurodegenerative and cancerous disorders in humans.

  5. High resolution solid-state NMR spectroscopy of the Yersinia pestis outer membrane protein Ail in lipid membranes

    International Nuclear Information System (INIS)

    Yao, Yong; Dutta, Samit Kumar; Park, Sang Ho; Rai, Ratan; Fujimoto, L. Miya; Bobkov, Andrey A.; Opella, Stanley J.; Marassi, Francesca M.

    2017-01-01

    The outer membrane protein Ail (Adhesion invasion locus) is one of the most abundant proteins on the cell surface of Yersinia pestis during human infection. Its functions are expressed through interactions with a variety of human host proteins, and are essential for microbial virulence. Structures of Ail have been determined by X-ray diffraction and solution NMR spectroscopy, but those samples contained detergents that interfere with functionality, thus, precluding analysis of the structural basis for Ail’s biological activity. Here, we demonstrate that high-resolution solid-state NMR spectra can be obtained from samples of Ail in detergent-free phospholipid liposomes, prepared with a lipid to protein molar ratio of 100. The spectra, obtained with 13 C or 1 H detection, have very narrow line widths (0.40–0.60 ppm for 13 C, 0.11–0.15 ppm for 1 H, and 0.46–0.64 ppm for 15 N) that are consistent with a high level of sample homogeneity. The spectra enable resonance assignments to be obtained for N, CO, CA and CB atomic sites from 75 out of 156 residues in the sequence of Ail, including 80% of the transmembrane region. The 1 H-detected solid-state NMR 1 H/ 15 N correlation spectra obtained for Ail in liposomes compare very favorably with the solution NMR 1 H/ 15 N TROSY spectra obtained for Ail in nanodiscs prepared with a similar lipid to protein molar ratio. These results set the stage for studies of the molecular basis of the functional interactions of Ail with its protein partners from human host cells, as well as the development of drugs targeting Ail.

  6. High resolution solid-state NMR spectroscopy of the Yersinia pestis outer membrane protein Ail in lipid membranes

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Yong; Dutta, Samit Kumar [Sanford Burnham Prebys Medical Discovery Institute (United States); Park, Sang Ho; Rai, Ratan [University of California San Diego, Department of Chemistry and Biochemistry (United States); Fujimoto, L. Miya; Bobkov, Andrey A. [Sanford Burnham Prebys Medical Discovery Institute (United States); Opella, Stanley J. [University of California San Diego, Department of Chemistry and Biochemistry (United States); Marassi, Francesca M., E-mail: fmarassi@sbp.edu [Sanford Burnham Prebys Medical Discovery Institute (United States)

    2017-03-15

    The outer membrane protein Ail (Adhesion invasion locus) is one of the most abundant proteins on the cell surface of Yersinia pestis during human infection. Its functions are expressed through interactions with a variety of human host proteins, and are essential for microbial virulence. Structures of Ail have been determined by X-ray diffraction and solution NMR spectroscopy, but those samples contained detergents that interfere with functionality, thus, precluding analysis of the structural basis for Ail’s biological activity. Here, we demonstrate that high-resolution solid-state NMR spectra can be obtained from samples of Ail in detergent-free phospholipid liposomes, prepared with a lipid to protein molar ratio of 100. The spectra, obtained with {sup 13}C or {sup 1}H detection, have very narrow line widths (0.40–0.60 ppm for {sup 13}C, 0.11–0.15 ppm for {sup 1}H, and 0.46–0.64 ppm for {sup 15}N) that are consistent with a high level of sample homogeneity. The spectra enable resonance assignments to be obtained for N, CO, CA and CB atomic sites from 75 out of 156 residues in the sequence of Ail, including 80% of the transmembrane region. The {sup 1}H-detected solid-state NMR {sup 1}H/{sup 15}N correlation spectra obtained for Ail in liposomes compare very favorably with the solution NMR {sup 1}H/{sup 15}N TROSY spectra obtained for Ail in nanodiscs prepared with a similar lipid to protein molar ratio. These results set the stage for studies of the molecular basis of the functional interactions of Ail with its protein partners from human host cells, as well as the development of drugs targeting Ail.

  7. In vivo evaluation of the efficacy of albendazole sulfoxide and albendazole sulfoxide loaded solid lipid nanoparticles against hydatid cyst.

    Science.gov (United States)

    Ahmadnia, Sara; Moazeni, Mohammad; Mohammadi-Samani, Soliman; Oryan, Ahmad

    2013-10-01

    Cystic echinococcosis (CE) is caused by the larval stage of Echinococcus granulosus, which in this disease the metacestode develop in visceral organs especially liver and lungs. The disease is present worldwide and affects humans as well as herbivores including cattle, sheep, camels, horses and others. Benzimidazole carbamate derivatives, such as mebendazole and albendazole, are currently used for chemotherapeutic treatment of CE in inoperable patients and have to be applied in high doses for extended periods of time, and therefore adverse side effects are frequently observed. This study was designed to evaluate and compare the in vivo effects of 0.5 mg/kg, BID, albendazole sulfoxide (ricobendazole) and two different therapeutic regimens of 0.5 mg/kg BID and 2 mg/kg every 48 h of albendazole sulfoxide loaded solid lipid nanoparticles. Albendazole sulfoxide loaded solid lipid nanoparticles was prepared by solvent diffusion-evaporation method. Fifty Balb/c mice were infected by intraperitoneal injection of protoscoleces and 8 months post infection, the infected mice were treated for 15 days with the above mentioned regimens. They were then euthanized and the size and weight of the cysts as well as their ultrastructural changes were investigated. Although the cysts showed reduced size and weight in the treated animals but these reductions were not statistically significant. The cysts in the animals which received albendazole sulfoxide loaded SLN every 48 h showed more ultrastructural modification. However, these ultrastructural changes should be supported by further biochemical and molecular studies before introducing it as an efficient therapeutic regimen for treatment of human and animal hydatid disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Effect of Solid Lipid Nanoparticle-Encapsulated Antimicrobial Peptide on Keratinocyte Migration and Wound Healing

    Science.gov (United States)

    2013-05-03

    strategy for Vitamin A supplements, retinol and retinyl palmitate, with improved cell uptake, as well as a more controlled, slower release rate, relative...W   Total  Cells   Live   Viability   K1   120000   86000   65%   K2   360000   270000   74%   K3   260000   200000

  9. Westinghouse Hanford Company effluent releases and solid waste management report for 1987: 200/600/1100 Areas

    International Nuclear Information System (INIS)

    Coony, F.M.; Howe, D.B.; Voigt, L.J.

    1988-05-01

    The purpose of this report is to fulfill the reporting requirements of US Department of Energy (DOE) Order 5484.1, Environmental Protection, Safety, and Health Protection Information Reporting Requirements. Quantities of airborne and liquid wastes discharged by Westinghouse Hanford Company (Westinghouse Hanford) in the 200 Areas, 600 Area, and 1100 Area in 1987 are presented in this report. Also, quantities of solid wastes stored and buried by Westinghouse Hanford in the 200 Areas are presented in this report. The report is also intended to demonstrate compliance with Westinghouse Hanford administrative control limit (ACL) values for radioactive constituents and with applicable guidelines and standards for nonradioactive constituents. The summary of airborne release data, liquid discharge data, and solid waste management data for calendar year (CY) 1987 and CY 1986 are presented in Table ES-1. Data values for 1986 are cited in Table ES-1 to show differences in releases and waste quantities between 1986 and 1987. 19 refs., 3 figs., 19 tabs

  10. [Orthogonal experiments for optimizing the formulation and preparation conditions of temozolomide solid lipid nanoparticles].

    Science.gov (United States)

    Dou, Mingjin; Huang, Guihua; Xi, Yanwei; Zhang, Na

    2008-10-01

    TMZ-SLN were prepared by emulsification-low temperature solidification method with stearic acid. The formulation and the preparation conditions were optimized by orthogonal experiments using entrapment efficiency as the evaluation index. The morphology was detected by transmission electron microscope. The Zeta potentials and the particle size distribution were evaluated by Laser Doppler Anemometry. The entrapment efficiencies and the drug release characteristics in vitro were assessed. The result showed that TMZ-SLN were concinnous and spherical in shape. The mean diameter (d(av) ) was 65.0 +/- 6.2 nm and the Zeta potential was -37.2 mV. The average entrapment efficiency was 58.9% +/- 1.21 %. The drug release behavior in vitro conformed to Higuchi Equation. The formation of a new material phase was testified by analysis of differential scanning calorimetry.

  11. Utilization of solid lipid nanoparticles for enhanced delivery of curcumin in cocultures of HT29-MTX and Caco-2 cells.

    Science.gov (United States)

    Guri, Anilda; Gülseren, Ibrahim; Corredig, Milena

    2013-09-01

    Solid lipid nanoparticles (SLN) have shown potential for encapsulation, protection and delivery of lipophilic functional components. In this study, we have investigated the capabilities of SLN to deliver a hydrophobic polyphenol compound, curcumin, in a coculture system of absorptive Caco-2 and mucus secreting HT29-MTX cells. The cells were grown on transport filters to mimic the human intestinal epithelium. Because of the hydrophobic nature of curcumin, its delivery to the basolateral compartment is expected to take place via a paracellular route. The changes in curcumin concentration in various compartments (i.e., apical, basolateral, mucus, and cell lysates) were evaluated using fluorescence spectroscopy. Two SLN systems were prepared with different emulsifying agents. The encapsulation of curcumin in SLN caused enhanced delivery compared to unencapsulated curcumin. In addition, SLN showed enhanced delivery compared to emulsion droplets containing liquid soy oil. The SLN were retained on the apical mucosal layer to a greater extent than emulsion droplets. The presence of SLN did not affect the integrity of the cellular junctions, as indicated by the TEER values, and the route of transport of the solid particles was simple diffusion, with permeability rates of about 7 × 10(-6) cm s(-1). Approximately 1% of total curcumin was delivered to the basolateral compartment, suggesting that most of the curcumin was absorbed and metabolized by the cell.

  12. Multi criteria decision making to select the best method for the preparation of solid lipid nanoparticles of rasagiline mesylate using analytic hierarchy process

    Directory of Open Access Journals (Sweden)

    Viveksarathi Kunasekaran

    2014-01-01

    Full Text Available The objective of this study was to select best method for the development of rasagiline mesylate (RM loaded nanoscale solid lipid particles using analytic hierarchy process (AHP. Improper method selection may lead to waste of time, loss of material and financial resources. One of the possibilities to overcome these difficulties, AHP was employed to find the suitable method. In the AHP, a decision of hierarchy was constructed with a goal, criteria, sub-criteria, and alternatives. After constructing the AHP, the expert choice software was used to compute the overall priority of criteria, sub-criteria and alternatives. The best alternative selected was based on the highest priority. Nanoscale solid lipid particles of RM was formulated by the selected microemulsion method (M4 and it shows the particle size, polydispersity index and zeta potential were within acceptable limits. Drug content and entrapment efficiency of the RM-solid lipid nanoparticles were 97.26% and 86.57%, respectively. This study concludes that the AHP was viable and effective tool for selecting a most suitable method for the fabrication of RM loaded nanoscale solid lipid particles.

  13. Investigation of Carnuba Wax as Matrix in the Formulation of Solid ...

    African Journals Online (AJOL)

    This study was carried out to investigate the drug entrapment efficiency, release potential and drug release mechanisms of solid lipid microparticles (SLMs) prepared with different concentrations of two non ionic surfactants using carnauba wax as the lipid matrix. SLMs were prepared by melt dispersion technique, whereby ...

  14. Evaluation of in-vitro cytotoxicity and cellular uptake efficiency of zidovudine-loaded solid lipid nanoparticles modified with Aloe Vera in glioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Joshy, K.S. [Department of Chemistry, CMS College Kottayam, Kerala (India); International and Inter University Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam 686 560, Kerala (India); Sharma, Chandra P. [Division of Biosurface Technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Poojappura, Thiruvananthapuram, Kerala (India); Kalarikkal, Nandakumar [International and Inter University Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam 686 560, Kerala (India); School of Pure and Applied Physics, Mahatma Gandhi University, Kottayam 686 560, Kerala (India); Sandeep, K. [International and Inter University Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam 686 560, Kerala (India); Thomas, Sabu, E-mail: sabuchathukulam@yahoo.co.uk [International and Inter University Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam 686 560, Kerala (India); School of Chemical Sciences, Mahatma Gandhi University, Kottayam 686 560, Kerala (India); Pothen, Laly A. [Department of Chemistry, Bishop Moore College, Mavelikkara, Kerala (India)

    2016-09-01

    Zidovudine loaded solid lipid nanoparticles of stearic acid modified with Aloe Vera (AV) have been prepared via simple emulsion solvent evaporation method which showed excellent stability at room temperature and refrigerated condition. The nanoparticles were examined by Fourier transform infrared spectroscopy (FT-IR), which revealed the overlap of the AV absorption peak with the absorption peak of modified stearic acid nanoparticles. The inclusion of AV to stearic acid decreased the crystallinity and improved the hydrophilicity of lipid nanoparticles and thereby improved the drug loading efficacy of lipid nanoparticles. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) imaging revealed that, the average particle size of unmodified (bare) nanoparticles was 45.66 ± 12.22 nm and modified solid lipid nanoparticles showed an average size of 265.61 ± 80.44 nm. Solid lipid nanoparticles with well-defined morphology were tested in vitro for their possible application in drug delivery. Cell culture studies using C6 glioma cells on the nanoparticles showed enhanced growth and proliferation of cells without exhibiting any toxicity. In addition, normal cell morphology and improved uptake were observed by fluorescence microscopy images of rhodamine labeled modified solid lipid nanoparticles compared with unmodified nanoparticles. The cellular uptake study suggested that these nanoparticles could be a promising drug delivery system to enhance the uptake of antiviral drug by brain cells and it could be a suitable drug carrier system for the treatment of HIV. - Highlights: • SLN of AZT-SA, AZT-SA-AV was developed • Better drug loading efficacy • Good uptake.

  15. Evaluation of in-vitro cytotoxicity and cellular uptake efficiency of zidovudine-loaded solid lipid nanoparticles modified with Aloe Vera in glioma cells

    International Nuclear Information System (INIS)

    Joshy, K.S.; Sharma, Chandra P.; Kalarikkal, Nandakumar; Sandeep, K.; Thomas, Sabu; Pothen, Laly A.

    2016-01-01

    Zidovudine loaded solid lipid nanoparticles of stearic acid modified with Aloe Vera (AV) have been prepared via simple emulsion solvent evaporation method which showed excellent stability at room temperature and refrigerated condition. The nanoparticles were examined by Fourier transform infrared spectroscopy (FT-IR), which revealed the overlap of the AV absorption peak with the absorption peak of modified stearic acid nanoparticles. The inclusion of AV to stearic acid decreased the crystallinity and improved the hydrophilicity of lipid nanoparticles and thereby improved the drug loading efficacy of lipid nanoparticles. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) imaging revealed that, the average particle size of unmodified (bare) nanoparticles was 45.66 ± 12.22 nm and modified solid lipid nanoparticles showed an average size of 265.61 ± 80.44 nm. Solid lipid nanoparticles with well-defined morphology were tested in vitro for their possible application in drug delivery. Cell culture studies using C6 glioma cells on the nanoparticles showed enhanced growth and proliferation of cells without exhibiting any toxicity. In addition, normal cell morphology and improved uptake were observed by fluorescence microscopy images of rhodamine labeled modified solid lipid nanoparticles compared with unmodified nanoparticles. The cellular uptake study suggested that these nanoparticles could be a promising drug delivery system to enhance the uptake of antiviral drug by brain cells and it could be a suitable drug carrier system for the treatment of HIV. - Highlights: • SLN of AZT-SA, AZT-SA-AV was developed • Better drug loading efficacy • Good uptake

  16. Slow heat release - solid fuel stove with acetat-trihydrate heat storage sodium; Slow heat release - Braendeovn med salthydratvarmelager

    Energy Technology Data Exchange (ETDEWEB)

    Zielke, U.; Bjerrum, M.; Noergaard, T. (Teknologisk Institut, Aarhus (Denmark))

    2012-07-01

    Of the 700,000 solid fuel stoves in Denmark, 600,000 are installed in permanent residences, and 100,000 are installed in summer cottages. Recent examinations have shown that in the heating season, these stoves contribute with a not negligible share of air pollution in the cities. The reason is often inexpedient firing and an inappropriate performance of the stove. In many cases the thermal output of the stove exceeds the heating demand of a modern residence; and the user typically reduces the stove's combustion air supply with the purpose of lowering the temperature of the accommodation space. The result is a sooting combustion followed by undesired and environmentally damaging emissions. In worst case the user fires throughout the night reducing the air to an absolutely minimum. In these situations the fuel smoulders all night, and the stove emits large amounts of undesirable and unhealthy emissions. By constructing the stove with a heat storage that can accumulate the heat from the stove and emit the heat later (when not firing), the problem with the unhealthy ''night firings'' should be eliminated. The project started with a pre-examination regarding suitable materials for a heat storage and a literature study of the subject. By using an OGC material, in this case sodiumacetat-trihydrat, the weight of the stove, in spite of the heat storage, could be held within reasonable frames, since 130 kg PCM can contain the same heat amount as 1,200 kg stone. The great challenge was to compensate for PCM's poor heat conductivities, to distribute the heat in the whole heat storage, making it melt regularly without generating local boiling. This problem was solved by construction measures. The system with sodiumacetat-trihydrat, which melts by 58 deg. C, came to function satisfactorily. 14 hours after the last firing, the temperature of the heat storage was 30 deg. C. The tests with PCM were followed by an extensive emission measuring program

  17. Projected tritium releases from F ampersand H Area Seepage Basins and the Solid Waste Disposal Facilities to Fourmile Branch

    International Nuclear Information System (INIS)

    Looney, B.B.; Haselow, J.S.; Lewis, C.M.; Harris, M.K.; Wyatt, D.E.; Hetrick, C.S.

    1993-01-01

    A large percentage of the radioactivity released to the environment by operations at the Savannah River Site (SRS) is due to tritium. Because of the relative importance of the releases of tritium from SRS facilities through the groundwater to the environment, periodic evaluation and documentation of the facility operational status, proposed corrective actions, and projected changes/reductions in tritium releases are justified. Past, current, and projected tritium releases from the F and H Area Seepage Basins and the Solid Waste Disposal Facilities (SWDF) to Fourmile Branch are described. Each section provides a brief operational history along with the current status and proposed corrective actions. A conceptual model and quantitative estimates of tritium release from the facilities into the groundwater and the environment are developed. Tritium releases from the F and H Area Seepage Basins are declining and will be further reduced by the implementation of a groundwater corrective action required by the Resource Conservation and Recovery Act (RCRA). Tritium releases from the SWDF have been relatively stable over the past 10 years. It is anticipated that SWDF tritium releases to Fourmile Branch will remain approximately at current levels for at least 10--20 years. Specific characterization activities are recommended to allow an improved projection of tritium flux and to assist in developing plans for plume mitigation. SRS and the South Carolina Department of Health and Environmental Control are developing groundwater corrective action plans for the SWDF. Portions of the SWDF are also regulated under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Reduction of tritium flux is one of the factors considered in the development of the RCRA/CERCLA groundwater corrective action. The final section of the document presents the sum of the projected tritium fluxes from these facilities to Fourmile Branch

  18. In vivo activity of released cell wall lipids of Mycobacterium bovis bacillus Calmette-Guérin is due principally to trehalose mycolates.

    Science.gov (United States)

    Geisel, Rachel E; Sakamoto, Kaori; Russell, David G; Rhoades, Elizabeth R

    2005-04-15

    The hallmark of Mycobacterium-induced pathology is granulomatous inflammation at the site of infection. Mycobacterial lipids are potent immunomodulators that contribute to the granulomatous response and are released in appreciable quantities by intracellular bacilli. Previously we investigated the granulomagenic nature of the peripheral cell wall lipids of Mycobacterium bovis bacillus Calmette-Guérin (BCG) by coating the lipids onto 90-microm diameter microspheres that were mixed into Matrigel matrix with syngeneic bone marrow-derived macrophages and injected i.p. into mice. These studies demonstrated that BCG lipids elicit proinflammatory cytokines and recruit leukocytes. In the current study we determined the lipids responsible for this proinflammatory effect. BCG-derived cell wall lipids were fractionated and purified by liquid chromatography and preparative TLC. The isolated fractions including phosphatidylinositol dimannosides, cardiolipin, phosphatidylglycerol, phosphatidylethanolamine, trehalose monomycolate, trehalose dimycolate, and mycoside B. Trehalose dimycolate, when delivered to bone marrow-derived murine macrophages, induced the greatest secretion of IL-1beta, IL-6, and TNF-alpha in vitro. Trehalose dimycolate similarly induced the greatest secretion of these proinflammatory cytokines in ex vivo matrices over the course of 12 days. Trehalose monomycolate and dimycolate also induced profound neutrophil recruitment in vivo. Experiments with TLR2 or TLR4 gene-deficient mice revealed no defects in responses to trehalose mycolates, although MyD88-deficient mice manifested significantly reduced cell recruitment and cytokine production. These results demonstrate that the trehalose mycolates, particularly trehalose dimycolate, are the most bioactive lipids in the BCG extract, inducing a proinflammatory cascade that influences granuloma formation.

  19. Lamellar crystalline self-assembly behaviour and solid lipid nanoparticles of a palmityl prodrug analogue of Capecitabine—A chemotherapy agent

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Xiaojuan; Moghaddam, Minoo J.; Sagnella, Sharon M.; Conn, Charlotte E.; Danon, Stephen J.; Waddington, Lynne J.; Drummond, Calum J. [CSIRO/MSE

    2014-09-24

    An amphiphile prodrug, 5'-deoxy-5-fluoro-N4-(palmityloxycarbonyl) cytidine or 5'-deoxy-5-fluoro-N4-(hexadecanaloxycarbonyl) cytidine (5-FCPal), consisting of the same head group as the commercially available chemotherapeutic agent Capecitabine, linked to a palmityl hydrocarbon chain via a carbamate bond is reported. Thermal analysis of this prodrug indicates that it melts at ~115 °C followed quickly by degradation beginning at ~120 °C. The neat solid 5-FCPal amphiphile acquires a lamellar crystalline arrangement with a d-spacing of 28.6 ± 0.3 Å, indicating interdigitation of the hydrocarbon chains. Under aqueous conditions, solid 5-FCPal is non-swelling and no lyotropic liquid crystalline phase formation is observed. In order to assess the in vitro toxicity and in vivo efficacy in colloidal form, solid lipid nanoparticles (SLNs) with an average size of ~700 nm were produced via high pressure homogenization. The in vitro toxicity of the 5-FCPal SLNs against several different cancer and normal cell types was assessed over a 48 h period, and IC50 values were comparable to those observed for Capecitabine. The in vivo efficacy of the 5-FCPal SLNs was then assessed against the highly aggressive mouse 4T1 breast cancer model. To do so, the prodrug SLNs were administered orally at 3 different dosages (0.1, 0.25, 0.5 mmol/mouse/day) and compared to Capecitabine delivered at the same dosages. After 21 days of receiving the treatments, the 0.5 mmol dose of 5-FCPal exhibited the smallest average tumour volume. Since 5-FCPal is activated in a similar manner to Capecitabine via a 3 step enzymatic pathway with the final step occurring preferentially at the tumour site, formulation of the prodrug into SLNs combines the advantage of selective, localized activation with the sustained release properties of nanostructured amphiphile self-assembly and multiple payload materials thereby potentially creating a more effective anticancer agent.

  20. The efficacy of Isotretinoin-loaded solid lipid nanoparticles in comparison to Isotrex® on acne treatment

    Directory of Open Access Journals (Sweden)

    Shiva Golmohammadzadeh

    2013-01-01

    Full Text Available Abstract: Topical retinoids are considered as the first line therapy in the treatment of acne vulgaris, but they are associated with cutaneous irritation. In this study, isotretinoin-loaded solid lipid nanoparticles(IT-SLN were prepared to treat the mild to moderate acne. Also using IT-SLN would minimize IT adverse effects in comparison to commercial product, Isotrex®. This study was conducted to prepare and characterize IT-SLN and assessing the efficiency of IT-SLN comparing to Isotrex® acne. IT-SLN was prepared using hot high pressure homogenization method.  IT-SLN contained 0.05% IT in 5% of lipid phase (Glyceryl monostearate- GMS and tween 80 (2.5 % w/v was used as surfactant in the aqueous phase. IT-SLN was characterized by particle size analyzing, differential scanning calorimetry and transmission electron microscopy. Encapsulation efficacy was also obtained using spectrophotometry. The efficacy of IT-SLN was evaluated in a randomized, single-blind, parallel-group study and compared with Isotrex®. Forty patients encountered in the study and divided in two groups. Treatment regimen was once-nightly topical administration accompanied with topical administration of clindamycin 2% solution twice a day for 8 weeks. The particle size of IT-SLN was around 60 nm with PDI of 0.4 and zeta potential was about -40 mV. Encapsulation efficacy of IT in SLN in crystalline form was 84±0.21%. IT-SLN produced significantly better treatment than Isotrex® in both non-inflammatory and inflammatory lesions according to its recovery percent after 8 weeks. Also IT-SLN gained better global assessment scores. Our results showed that IT-SLN had higher efficacy than Isotrex® to clear non-inflammatory and inflammatory lesions.

  1. 'Boomerang'-like insertion of a fusogenic peptide in a lipid membrane revealed by solid-state 19F NMR.

    Science.gov (United States)

    Afonin, Sergii; Dürr, Ulrich H N; Glaser, Ralf W; Ulrich, Anne S

    2004-02-01

    Solid state (19)F NMR revealed the conformation and alignment of the fusogenic peptide sequence B18 from the sea urchin fertilization protein bindin embedded in flat phospholipid bilayers. Single (19)F labels were introduced into nine distinct positions along the wild-type sequence by substituting each hydrophobic amino acid, one by one, with L-4-fluorophenylglycine. Their anisotropic chemical shifts were measured in uniaxially oriented membrane samples and used as orientational constraints to model the peptide structure in the membrane-bound state. Previous (1)H NMR studies of B18 in 30% TFE and in detergent micelles had shown that the peptide structure consists of two alpha-helical segments that are connected by a flexible hinge. This helix-break-helix motif was confirmed here by the solid-state (19)F NMR data, while no other secondary structure (beta-sheet, 3(10)-helix) was compatible with the set of orientational constraints. For both alpha-helical segments we found that the helical conformation extends all the way to the respective N- and C-termini of the peptide. Analysis of the corresponding tilt and azimuthal rotation angles showed that the N-terminal helix of B18 is immersed obliquely into the bilayer (at a tilt angle tau approximately 54 degrees), whereas the C-terminus is peripherally aligned (tau approximately 91 degrees). The azimuthal orientation of the two segments is consistent with the amphiphilic distribution of side-chains. The observed 'boomerang'-like mode of insertion into the membrane may thus explain how peptide binding leads to lipid dehydration and acyl chain perturbation as a prerequisite for bilayer fusion to occur. Copyright 2004 John Wiley & Sons, Ltd.

  2. Effects of biosurfactants, mannosylerythritol lipids, on the hydrophobicity of solid surfaces and infection behaviours of plant pathogenic fungi.

    Science.gov (United States)

    Yoshida, S; Koitabashi, M; Nakamura, J; Fukuoka, T; Sakai, H; Abe, M; Kitamoto, D; Kitamoto, H

    2015-07-01

    To investigate the effects of mannosylerythritol lipids (MELs) on the hydrophobicity of solid surfaces, their suppressive activity against the early infection behaviours of several phytopathogenic fungal conidia, and their suppressive activity against disease occurrences on fungal host plant leaves. The changes in the hydrophobicity of plastic film surfaces resulting from treatments with MEL solutions (MEL-A, MEL-B, MEL-C and isoMEL-B) and synthetic surfactant solutions were evaluated based on the changes in contact angles of water droplets placed on the surfaces. The droplet angles on surfaces treated with MELs were verified to decrease within 100 s after placement, with contact angles similar to those observed on Tween 20-treated surfaces, indicating decreases in surface hydrophobicity after MEL treatments. Next, conidial germination, germ tube elongation and the formation of appressorium of Blumeria graminis f. sp. tritici, Colletotrichum dematium, Glomerella cingulata and Magnaporthe grisea were evaluated on plastic surfaces that were pretreated with surfactant solutions. On the surfaces of MEL-treated plastic film, inhibition of conidial germination, germ tube elongation, and suppression of appressoria formation tended to be observed, although the level of effect was dependent on the combination of fungal species and type of MEL. Inoculation tests revealed that the powdery mildew symptom caused by B. graminis f. sp. tritici was significantly suppressed on wheat leaf segments treated with MELs. MELs exhibited superior abilities in reducing the hydrophobicity of solid surfaces, and have the potential to suppress powdery mildew in wheat plants, presumably due to the inhibition of conidial germination. This study provides significant evidence of the potential for MELs to be used as novel agricultural chemical pesticides. © 2015 The Society for Applied Microbiology.

  3. Solid lipid nanoparticles of amphotericin B (AmbiOnp): in vitro and in vivo assessment towards safe and effective oral treatment module.

    Science.gov (United States)

    Chaudhari, Manisha B; Desai, Preshita P; Patel, Pratikkumar A; Patravale, Vandana B

    2016-08-01

    Amphotericin B, a gold standard broad spectrum antibiotic used in treatment of systemic fungal infections and visceral leishmaniasis, though is effective parenterally offers severe nephrotoxicity whereas the oral delivery is reported to give very meager oral bioavailability. Thus, to alleviate the toxicity and to improve oral bioavailability, an effective oral delivery approach in the form of solid lipid nanoparticles of amphotericin B (AmbiOnp) was reported earlier by our group. In this investigation, we report the predominant formation of nontoxic superaggregated form of amphotericin B, resulting from the probe sonication-assisted nanoprecipitation technique. The developed formulation was further confirmed to retain this nontoxic form and was found to be stable over the varied gastrointestinal conditions. Further, in vitro antifungal activity of AmbiOnp against Candida albicans showed minimum inhibitory concentration value of 7.812 μg/mL attributed to controlled release of drug from nanoparticulate matrix. In vivo pharmacokinetic studies revealed a relative bioavailability of AmbiOnp to be 1.05-fold with a Cmax of 1109.31 ± 104.79 ng/mL at the end of 24 h which was comparable to Cmax of 1417.49 ± 85.52 ng/mL achieved with that of marketed formulation (Fungizone®) given intravenously establishing efficacy of AmbiOnp. In vivo biodistribution studies indicated very low levels of Amphotericin B in kidneys when given as AmbiOnp as compared to that of marketed formulation proving its safety and was further corroborated by renal toxicity studies. Further, the formulations were found to be stable under refrigeration condition over a period of 3 months.

  4. Determination of radiation-induced hydrocarbons in processed food and complex lipid matrices. A new solid phase extraction (SPE) method for detection of irradiated components in food

    International Nuclear Information System (INIS)

    Hartmann, M.; Ammon, J.; Berg, H.

    1997-01-01

    Detection of irradiated components in processed food with complex lipid matrices can be affected by two problems. First, the processed food may contain only a small amount of the irradiated component, and the radiation-induced hydrocarbons may be diluted throughout the lipid matrix of the whole food. Second, in complex lipid matrices, the detection of prior irradiation is often disturbed by fat-associated compounds. In these cases, common solid phase extraction (SPE) Florisil clean-up alone is inadequate in the detection of prior irradiation. Subsequent SPE argentation chromatography of the Florisil eluate allows the measurement of small amounts of irradiated lipid-containing ingredients in processed food as well as the detection of prior irradiation in complex lipid matrices such as paprika and chilli. SPE argetation chromatography is the first method available for the selective enrichment of radiation-specific hydrocarbons from even complex lipid matrices, thus enabling the detection of irradiation does as low as 0.025 kGy. Furthermore, by using radiation-induced hydrocarbons in the detection of prior irradiation of paprika and chilli powder, a second independent method, the first being measurement of thermoluminescence, is available for the analysis of these matrices. Such analysis could be achieved by using this highly sensitive, cheap and easy to perform combined SPE Florisil/argentation chromatography method, without the need for sophisticated techniques like SFE-GC/MS or LC-GC/MS, so that highly sensitive detection of prior irradiation colud be performed in almost every laboratory

  5. Lipid-drug-conjugate (LDC) solid lipid nanoparticles (SLN) for the delivery of nicotine to the oral cavity - optimization of nicotine loading efficiency.

    Science.gov (United States)

    Ding, Yuan; Nielsen, Kent A; Nielsen, Bruno P; Bøje, Niels W; Müller, Rainer H; Pyo, Sung Min

    2018-03-12

    Nicotine, obtained from tobacco leaves, has been used to promote the cessation of smoking and reduce the risk of COPD and lung cancer. Incorporating the active in lipid nanoparticles is an effective tool to minimize its irritation potential and to use the particles as intermediate to produce final products. However, as a hydrophilic active, it is a challenge to prepare nicotine loaded lipid nanoparticles with high drug loading. In this study, lipid-drug-conjugates (LDC) were formed by nicotine and different fatty acids to enable the production of sufficiently loaded nicotine lipid nanoparticles. The encapsulation efficiency of nicotine in LDC-containing SLN was about 50%, which increased at least fourfold compared to the non-LDC formulations (around 10%) due to the increased lipophilicity of nicotine by strong interactions between positively charged nicotine and negatively charged fatty acids (formation of LDCs). The z-average of all formulations (150 to 350 nm) proved to be in the required submicron size range with a narrow size distribution. In summary, nicotine loaded LDC lipid nanoparticles with high drug loading were successfully developed with Kolliwax® S and stearic acid as counter-ion forming the LDC and hydrogenated sunflower oil (HSO) as lipid particle matrix. Copyright © 2018. Published by Elsevier B.V.

  6. Solid lipid nanoparticles carrying chemotherapeutic drug across the blood-brain barrier through insulin receptor-mediated pathway.

    Science.gov (United States)

    Kuo, Yung-Chih; Shih-Huang, Chun-Yuan

    2013-09-01

    Carmustine (BCNU)-loaded solid lipid nanoparticles (SLNs) were grafted with 83-14 monoclonal antibody (MAb) (83-14 MAb/BCNU-SLNs) and applied to the brain-targeting delivery. Human brain-microvascular endothelial cells (HBMECs) incubated with 83-14 MAb/BCNU-SLNs were stained to demonstrate the interaction between the nanocarriers and expressed insulin receptors (IRs). The results revealed that the particle size of 83-14 MAb/BCNU-SLNs decreased with an increasing weight percentage of Dynasan 114 (DYN). Storage at 4 °C for 6 weeks slightly deformed the colloidal morphology. In addition, poloxamer 407 on 83-14 MAb/BCNU-SLNs induced cytotoxicity to RAW264.7 cells and inhibited phagocytosis by RAW264.7 cells. An increase in the weight percentage of DYN from 0% to 67% slightly reduced the viability of RAW264.7 cells and promoted phagocytosis. Moreover, the transport ability of 83-14 MAb/BCNU-SLNs across the blood-brain barrier (BBB) in vitro enhanced with an increasing weight percentage of Tween 80. 83-14 MAb on MAb/BCNU-SLNs stimulated endocytosis by HBMECs via IRs and enhanced the permeability of BCNU across the BBB. 83-14 MAb/BCNU-SLNs can be a promising antitumor drug delivery system for transporting BCNU to the brain.

  7. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population.

    Science.gov (United States)

    Cox, Katherine H M; Pipingas, Andrew; Scholey, Andrew B

    2015-05-01

    Curcumin possesses many properties which may prevent or ameliorate pathological processes underlying age-related cognitive decline, dementia or mood disorders. These benefits in preclinical studies have not been established in humans. This randomized, double-blind, placebo-controlled trial examined the acute (1 and 3 h after a single dose), chronic (4 weeks) and acute-on-chronic (1 and 3 h after single dose following chronic treatment) effects of solid lipid curcumin formulation (400 mg as Longvida®) on cognitive function, mood and blood biomarkers in 60 healthy adults aged 60-85. One hour after administration curcumin significantly improved performance on sustained attention and working memory tasks, compared with placebo. Working memory and mood (general fatigue and change in state calmness, contentedness and fatigue induced by psychological stress) were significantly better following chronic treatment. A significant acute-on-chronic treatment effect on alertness and contentedness was also observed. Curcumin was associated with significantly reduced total and LDL cholesterol and had no effect on hematological safety measures. To our knowledge this is the first study to examine the effects of curcumin on cognition and mood in a healthy older population or to examine any acute behavioral effects in humans. Results highlight the need for further investigation of the potential psychological and cognitive benefits of curcumin in an older population. © The Author(s) 2014.

  8. Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches.

    Science.gov (United States)

    Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

    2016-01-01

    Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications.

  9. Physiochemical Characterization and Release Rate Studies of SolidDispersions of Ketoconazole with Pluronic F127 and PVP K-30

    Science.gov (United States)

    Kumar, Pankaj; Mohan, Chander; KanamSrinivasan Uma Shankar, Mara; Gulati, Monica

    2011-01-01

    In the present study solid dispersions of the antifungal drug Ketoconazole were prepared with Pluronic F-127 and PVP K-30 with an intention to improve its dissolution properties. Investigations of the properties of the dispersions were performed using release studies, Differential scanning calorimetery (DSC), X-ray powder diffraction (XRD) and Fourier transform infrared (FTIR). The results obtained showed that the rate of dissolution of Ketoconazole was considerably improved when formulated in solid dispersions with PVP K-30 and Pluronic F-127 as compared with pure drug and physical mixtures. The results from DSC and XRD studies showed the transition of crystalline nature of drug to amorphous form, while FTIR studies demonstrated the absence of drug-carriers interaction. PMID:24250403

  10. Determining the Release of Radionuclides from Tank 18F Waste Residual Solids: FY2016 Report

    Energy Technology Data Exchange (ETDEWEB)

    King, William D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Hobbs, David T. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-08-12

    Pore water leaching studies were conducted on actual Savannah River Site (SRS) Tank 18F residual waste solids to support Liquid Waste tank closure efforts. A test methodology was developed during previous simulant testing to produce slurries of tank residual solids and grout-representative solids in grout pore water solutions (based on SRS groundwater compositions) with pH and Eh values expected during the aging of the closed waste tank. The target conditions are provided below where the initial pore water has a reducing potential and a relatively high pH (Reducing Region II). The pore water is expected to become increasingly oxidizing with time (Oxidizing Region II) and during the latter stages of aging (Oxidizing Region III) the pH is expected to decrease. For the reducing case, tests were conducted with both unwashed and washed Tank 18F residual solids. For the oxidizing cases (Oxidizing Regions II and III), all samples were washed with simulated grout pore water solutions prior to testing, since it is expected that these conditions will occur after considerable pore water solution has passed through the system. For the reducing case, separate tests were conducted with representative ground grout solids and with calcium carbonate reagent, which is the grout phase believed to be controlling the pH. Ferrous sulfide (FeS) solids were also added to the reducing samples to lower the slurry Eh value. Calcium carbonate solids were used as the grout-representative solid phase for each of the oxidizing cases. Air purge-gas with and without CO2 removed was transferred through the oxidizing test samples and nitrogen purge-gas was transferred through the reducing test samples during leach testing. The target pH values were achieved to within 0.5 pH units for all samples. Leaching studies were conducted over an Eh range of approximately 0.7 V. However, the highest and lowest Eh values achieved of ~+0.5 V and ~-0.2 V were

  11. Analytical model for release calculations in solid thin-foils ISOL targets

    Energy Technology Data Exchange (ETDEWEB)

    Egoriti, L. [Belgian Nuclear Research Centre (SCK-CEN), Boeretang 200, B-2400 Mol (Belgium); Politecnico di Milano, Department of Energy, CeSNEF-Nuclear Engineering Division, Via Ponzio, 34/3, 20133 Milano (Italy); Boeckx, S. [Belgian Nuclear Research Centre (SCK-CEN), Boeretang 200, B-2400 Mol (Belgium); ICTEAM Inst., Univ. Catholique de Louvain, Louvain-la-Neuve (Belgium); Ghys, L. [Belgian Nuclear Research Centre (SCK-CEN), Boeretang 200, B-2400 Mol (Belgium); Houngbo, D., E-mail: donald.houngbo@sckcen.be [Belgian Nuclear Research Centre (SCK-CEN), Boeretang 200, B-2400 Mol (Belgium); Department of Flow, Heat and Combustion Mechanics, Gent University (UGent), St.-Pietersnieuwstraat 41, B-9000 Gent (Belgium); Popescu, L. [Belgian Nuclear Research Centre (SCK-CEN), Boeretang 200, B-2400 Mol (Belgium)

    2016-10-01

    A detailed analytical model has been developed to simulate isotope-release curves from thin-foils ISOL targets. It involves the separate modeling of diffusion and effusion inside the target. The former has been modeled using both first and second Fick's law. The latter, effusion from the surface of the target material to the end of the ionizer, was simulated with the Monte Carlo code MolFlow+. The calculated delay-time distribution for this process was then fitted using a double-exponential function. The release curve obtained from the convolution of diffusion and effusion shows good agreement with experimental data from two different target geometries used at ISOLDE. Moreover, the experimental yields are well reproduced when combining the release fraction with calculated in-target production.

  12. Lipid-coated hollow mesoporous silica nanospheres for co-delivery of doxorubicin and paclitaxel: Preparation, sustained release, cellular uptake and pharmacokinetics

    International Nuclear Information System (INIS)

    Qiu, Yang; Wu, Chao; Jiang, Jie; Hao, Yanna; Zhao, Ying; Xu, Jie; Yu, Tong; Ji, Peng

    2017-01-01

    A carrier consisting of lipid-coated hollow mesoporous silica nanospheres (L-HMSN) was produced for the combination of the water-insoluble drug (paclitaxel, PTX) and the water-soluble drug (doxorubicin, DOX). DOX was adsorbed into the nanoscale hollow structure of the hollow mesoporous silica nanospheres (HMSN) by adsorption and PTX was wrapped in the phospholipid layer of the HMSN surface by lipid film hydration method. The characterization results showed that DOX and PTX were present in the nanopheres in an amorphous state. The loaded L-HMSN (DOX/PTX@L-HMSN) in vitro drug release showed a sustained release in phosphate buffered solution (PBS) at pH 6.8 and 0.001%SDS. The cellular uptake experiment indicated that L-HMSN was successfully taken up by A549 cells. In addition, the combination of DOX and PTX in L-HMSN exhibited a marked synergistic effect in inhibiting the proliferation of A549 cells. The pharmacokinetic study demonstrated that L-HMSN could significantly improve the relative bioavailability of DOX and PTX. These results confirm that L-HMSN is a promising carrier for successful drug combination. - Highlights: • L-HMSN as a platform is used for combination of DOX and PTX • The drug delivery system demonstrates synergy effect in inhibiting A549 cell proliferation • The drug delivery system slowly releases the drugs and improves drug absorption

  13. Lipid-coated hollow mesoporous silica nanospheres for co-delivery of doxorubicin and paclitaxel: Preparation, sustained release, cellular uptake and pharmacokinetics

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Yang; Wu, Chao, E-mail: wuchao27@126.com; Jiang, Jie; Hao, Yanna; Zhao, Ying; Xu, Jie; Yu, Tong; Ji, Peng

    2017-02-01

    A carrier consisting of lipid-coated hollow mesoporous silica nanospheres (L-HMSN) was produced for the combination of the water-insoluble drug (paclitaxel, PTX) and the water-soluble drug (doxorubicin, DOX). DOX was adsorbed into the nanoscale hollow structure of the hollow mesoporous silica nanospheres (HMSN) by adsorption and PTX was wrapped in the phospholipid layer of the HMSN surface by lipid film hydration method. The characterization results showed that DOX and PTX were present in the nanopheres in an amorphous state. The loaded L-HMSN (DOX/PTX@L-HMSN) in vitro drug release showed a sustained release in phosphate buffered solution (PBS) at pH 6.8 and 0.001%SDS. The cellular uptake experiment indicated that L-HMSN was successfully taken up by A549 cells. In addition, the combination of DOX and PTX in L-HMSN exhibited a marked synergistic effect in inhibiting the proliferation of A549 cells. The pharmacokinetic study demonstrated that L-HMSN could significantly improve the relative bioavailability of DOX and PTX. These results confirm that L-HMSN is a promising carrier for successful drug combination. - Highlights: • L-HMSN as a platform is used for combination of DOX and PTX • The drug delivery system demonstrates synergy effect in inhibiting A549 cell proliferation • The drug delivery system slowly releases the drugs and improves drug absorption.

  14. Aminoclay–lipid hybrid composite as a novel drug carrier of fenofibrate for the enhancement of drug release and oral absorption

    Directory of Open Access Journals (Sweden)

    Yang L

    2016-03-01

    Full Text Available Liang Yang, Yating Shao, Hyo-Kyung Han BK Plus Project Team, College of Pharmacy, Dongguk University, Goyang, South Korea Abstract: This study aimed to prepare the aminoclay–lipid hybrid composite to enhance the drug release and improve the oral bioavailability of poorly water-soluble fenofibrate. Antisolvent precipitation coupled with an immediate freeze-drying method was adopted to incorporate fenofibrate into aminoclay–lipid hybrid composite (ALC. The optimal composition of the ALC formulation was determined as the ratios of aminoclay to krill oil of 3:1 (w/w, krill oil to fenofibrate of 2:1 (w/w, and antisolvent to solvent of 6:4 (v/v. The morphological characteristics of ALC formulation were determined using scanning electron microscopy, differential scanning calorimetry, and X-ray powder diffraction, which indicated microcrystalline state of fenofibrate in ALC formulation. The ALC formulation achieved almost complete dissolution within 30 minutes, whereas the untreated powder and physical mixture exhibited less than 15% drug release. Furthermore, ALC formulation effectively increased the peak plasma concentration (Cmax and area under the curve (AUC of fenofibric acid (an active metabolite in rats by approximately 13- and seven-fold, respectively. Furthermore, ALC formulation exhibited much lower moisture sorption behavior than the lyophilized formulation using sucrose as a cryoprotectant. Taken together, the present findings suggest that ALC formulation is promising for improving the oral absorption of poorly soluble fenofibrate. Keywords: aminoclay, omega-3 phospholipids, fenofibrate, drug release, oral absorption 

  15. Determining the release of radionuclides from tank waste residual solids. FY2015 report

    Energy Technology Data Exchange (ETDEWEB)

    King, William D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Hobbs, David T. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2015-09-11

    Methodology development for pore water leaching studies has been continued to support Savannah River Site High Level Waste tank closure efforts. For FY2015, the primary goal of this testing was the achievement of target pH and Eh values for pore water solutions representative of local groundwater in the presence of grout or grout-representative (CaCO3 or FeS) solids as well as waste surrogate solids representative of residual solids expected to be present in a closed tank. For oxidizing conditions representative of a closed tank after aging, a focus was placed on using solid phases believed to be controlling pH and Eh at equilibrium conditions. For three pore water conditions (shown below), the target pH values were achieved to within 0.5 pH units. Tank 18 residual surrogate solids leaching studies were conducted over an Eh range of approximately 630 mV. Significantly higher Eh values were achieved for the oxidizing conditions (ORII and ORIII) than were previously observed. For the ORII condition, the target Eh value was nearly achieved (within 50 mV). However, Eh values observed for the ORIII condition were approximately 160 mV less positive than the target. Eh values observed for the RRII condition were approximately 370 mV less negative than the target. Achievement of more positive and more negative Eh values is believed to require the addition of non-representative oxidants and reductants, respectively. Plutonium and uranium concentrations measured during Tank 18 residual surrogate solids leaching studies under these conditions (shown below) followed the general trends predicted for plutonium and uranium oxide phases, assuming equilibrium with dissolved oxygen. The highest plutonium and uranium concentrations were observed for the ORIII condition and the lowest concentrations were observed for the RRII condition. Based on these results, it is recommended that these test methodologies be used to

  16. Novel Solid Encapsulation of Ethylene Gas Using Amorphous α-Cyclodextrin and the Release Characteristics.

    Science.gov (United States)

    Ho, Binh T; Bhandari, Bhesh R

    2016-05-04

    This research investigated the encapsulation of ethylene gas into amorphous α-cyclodextrins (α-CDs) at low (LM) and high (HM) moisture contents at 1.0-1.5 MPa for 24-120 h and its controlled release characteristics at 11.2-52.9% relative humidity (RH) for 1-168 h. The inclusion complexes (ICs) were characterized using X-ray diffractometry (XRD), nuclear magnetic resonance spectroscopy (CP-MAS (13)C NMR), and scanning electron microscopy (SEM). Ethylene concentrations in the ICs were from 0.45 to 0.87 mol of ethylene/mol CD and from 0.42 to 0.54 mol of ethylene/mol CD for LM and HM α-CDs, respectively. Ethylene gas released from the encapsulated powder at higher rates with increasing RH. An analysis of release kinetics using Avrami's equation showed that the LM and HM amorphous α-CDs were not associated with significant differences in release constant k and parameter n for any given RH condition. NMR spectra showed the presence of the characteristic carbon-carbon double bond of ethylene gas in the encapsulated α-CD powder.

  17. Approaches to evaluating weathering effects on release of engineered nanomaterials from solid matrices

    Science.gov (United States)

    Increased production and use of engineered nanomaterials (ENMs) over the past decade has increased the potential for the transport and release of these materials into the environment. Here we present results of two separate studies designed to simulate the effects of weathering o...

  18. The Use of Quasi-Isothermal Modulated Temperature Differential Scanning Calorimetry for the Characterization of Slow Crystallization Processes in Lipid-Based Solid Self-Emulsifying Systems

    OpenAIRE

    Otun, Sarah O.; Meehan, Elizabeth; Qi, Sheng; Craig, Duncan Q. M.

    2014-01-01

    Purpose Slow or incomplete crystallization may be a significant manufacturing issue for solid lipid-based dosage forms, yet little information is available on this phenomenon. In this investigation we suggest a novel means by which slow solidification may be monitored in Gelucire 44/14 using quasi-isothermal modulated temperature DSC (QiMTDSC). Methods Conventional linear heating and cooling DSC methods were employed, along with hot stage microscopy (HSM), for basic thermal profiling of Geluc...

  19. Lipid nanoparticles for the delivery of poorly water-soluble drugs.

    Science.gov (United States)

    Bunjes, Heike

    2010-11-01

    This review discusses important aspects of lipid nanoparticles such as colloidal lipid emulsions and, in particular, solid lipid nanoparticles as carrier systems for poorly water-soluble drugs, with a main focus on the parenteral and peroral use of these carriers. A short historical background of the development of colloidal lipid emulsions and solid lipid nanoparticles is provided and their similarities and differences are highlighted. With regard to drug incorporation, parameters such as the chemical nature of the particle matrix and the physicochemical nature of the drug, effects of drug partition and the role of the particle interface are discussed. Since, because of the crystalline nature of their lipid core, solid lipid nanoparticles display some additional important features compared to emulsions, their specificities are introduced in more detail. This mainly includes their solid state behaviour (crystallinity, polymorphism and thermal behaviour) and the consequences of their usually non-spherical particle shape. Since lipid nanoemulsions and -suspensions are also considered as potential means to alter the pharmacokinetics of incorporated drug substances, some underlying basic considerations, in particular concerning the drug-release behaviour of such lipid nanodispersions on dilution, are addressed as well. Colloidal lipid emulsions and solid lipid nanoparticles are interesting options for the delivery of poorly water-soluble drug substances. Their specific physicochemical properties need, however, to be carefully considered to provide a rational basis for their development into effective carrier systems for a given delivery task. © 2010 The Author. Journal compilation © 2010 Royal Pharmaceutical Society of Great Britain.

  20. Second Order Kinetic Modeling of Headspace Solid Phase Microextraction of Flavors Released from Selected Food Model Systems

    Directory of Open Access Journals (Sweden)

    Jiyuan Zhang

    2014-09-01

    Full Text Available The application of headspace-solid phase microextraction (HS-SPME has been widely used in various fields as a simple and versatile method, yet challenging in quantification. In order to improve the reproducibility in quantification, a mathematical model with its root in psychological modeling and chemical reactor modeling was developed, describing the kinetic behavior of aroma active compounds extracted by SPME from two different food model systems, i.e., a semi-solid food and a liquid food. The model accounted for both adsorption and release of the analytes from SPME fiber, which occurred simultaneously but were counter-directed. The model had four parameters and their estimated values were found to be more reproducible than the direct measurement of the compounds themselves by instrumental analysis. With the relative standard deviations (RSD of each parameter less than 5% and root mean square error (RMSE less than 0.15, the model was proved to be a robust one in estimating the release of a wide range of low molecular weight acetates at three environmental temperatures i.e., 30, 40 and 60 °C. More insights of SPME behavior regarding the small molecule analytes were also obtained through the kinetic parameters and the model itself.

  1. Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

    Directory of Open Access Journals (Sweden)

    Madureira AR

    2016-08-01

    Full Text Available Ana Raquel Madureira,1 Sara Nunes,2 Débora A Campos,1 João C Fernandes,2 Cláudia Marques,3 Monica Zuzarte,2 Beatriz Gullón,1 Luís M Rodríguez-Alcalá,1 Conceição Calhau,3,4 Bruno Sarmento,5–7 Ana Maria Gomes,1 Maria Manuela Pintado,1 Flávio Reis2 1Catholic University of Portugal, CBQF – Center for Biotechnology and Fine Chemistry – Associate Laboratory, Faculty of Biotechnology, Porto, Portugal; 2Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI, Faculty of Medicine, and CNC.IBILI Consortium, University of Coimbra, Coimbra, Portugal; 3Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal; 4Center for Health Technology and Services Research (CINTESIS, Porto, Portugal; 5Department of Pharmaceutical Sciences, Institute of Health Sciences-North, CESPU, Gandra, Portugal; 6“I3S” Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal; 7INEB, Institute of Biomedical Engineering, University of Porto, Porto, Portugal Abstract: Rosmarinic acid (RA possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL were evaluated for cell (lymphocytes viability, necrosis and apoptosis, and antioxidant

  2. 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 . In this work, the inclusion of a P-gp inhibitor, chlorpheniramine, and chloroquine in a lipid-based nanoparticle carrier is proposed, with the aim of ensuring that adequate drug levels are attained, so as to overcome drug resistance. Methods: The nanoparticles...

  3. Enhanced intracellular delivery and antibacterial efficacy of enrofloxacin-loaded docosanoic acid solid lipid nanoparticles against intracellular Salmonella.

    Science.gov (United States)

    Xie, Shuyu; Yang, Fei; Tao, Yanfei; Chen, Dongmei; Qu, Wei; Huang, Lingli; Liu, Zhenli; Pan, Yuanhu; Yuan, Zonghui

    2017-01-23

    Enrofloxacin-loaded docosanoic acid solid lipid nanoparticles (SLNs) with different physicochemical properties were developed to enhance activity against intracellular Salmonella. Their cellular uptake, intracellular elimination and antibacterial activity were studied in RAW 264.7 cells. During the experimental period, SLN-encapsulated enrofloxacin accumulated in the cells approximately 27.06-37.71 times more efficiently than free drugs at the same extracellular concentration. After incubation for 0.5 h, the intracellular enrofloxacin was enhanced from 0.336 to 1.147 μg/mg of protein as the sizes of nanoparticles were increased from 150 to 605 nm, and from 0.960 to 1.147 μg/mg of protein when the charge was improved from -8.1 to -24.9 mv. The cellular uptake was more significantly influenced by the size than it was by the charge, and was not affected by whether the charge was positive or negative. The elimination of optimal SLN-encapsulated enrofloxacin from the cells was significantly slower than that of free enrofloxacin after removing extracellular drug. The inhibition effect against intracellular Salmonella CVCC541 of 0.24 and 0.06 μg/mL encapsulated enrofloxacin was stronger than 0.6 μg/mL free drug after all of the incubation periods and at 48 h, respectively. Docosanoic acid SLNs are thus considered as a promising carrier for intracellular bacterial treatment.

  4. Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human inflammatory bowel disease whole-blood model.

    Science.gov (United States)

    Serpe, Loredana; Canaparo, Roberto; Daperno, Marco; Sostegni, Raffaello; Martinasso, Germana; Muntoni, Elisabetta; Ippolito, Laura; Vivenza, Nicoletta; Pera, Angelo; Eandi, Mario; Gasco, Maria Rosa; Zara, Gian Paolo

    2010-03-18

    Standard treatment for inflammatory bowel diseases (IBD) necessitates frequent intake of anti-inflammatory and/or immunosuppressive drugs, leading to significant adverse events. To evaluate the role solid lipid nanoparticles (SLN) play as drug delivery system in enhancing anti-inflammatory activity for drugs such as dexamethasone and butyrate in a human inflammatory bowel diseases whole-blood model. ELISA assay and the peripheral blood mononuclear cell (PBMC) cytokine mRNA expression levels were evaluated by quantitative SYBR Green real-time RT-PCR to determine the IL-1beta, TNF-alpha, IFN-gamma and IL-10 secretion in inflammatory bowel diseases patients' PBMC culture supernatants. There was a significant decrease in IL-1beta (p<0.01) and TNF-alpha (p<0.001) secretion, whilst IL-10 (p<0.05) secretion significantly increased after cholesteryl butyrate administration, compared to that of butyrate alone at the highest concentration tested (100 microM), at 24h exposure. There was a significant decrease in IL-1beta (p<0.01), TNF-alpha (p<0.001) and IL-10 (p<0.001) secretion after dexamethasone loaded SLN administration, compared to dexamethasone alone at the highest concentration tested (250 nM) at 24h exposure. No IFN-gamma was detected under any conditions and no cytotoxic effects observed even at the highest concentration tested. The incorporation of butyrate and dexamethasone into SLN has a significant positive anti-inflammatory effect in the human inflammatory bowel disease whole-blood model. Copyright 2010 Elsevier B.V. All rights reserved.

  5. Development of "all natural" layer-by-layer redispersible solid lipid nanoparticles by nano spray drying technology.

    Science.gov (United States)

    Wang, Taoran; Hu, Qiaobin; Zhou, Mingyong; Xia, Yan; Nieh, Mu-Ping; Luo, Yangchao

    2016-10-01

    Solid lipid nanoparticles (SLNs) have gained tremendous attraction as carriers for controlled drug delivery. Despite numerous advances in the field, one long-standing historical challenge for their practical applications remains unmet: redispersibility after drying. In this work, a novel design of SLNs using a layer-by-layer (LbL) technique was developed and the formulations were optimized by surface response methodology (Box-Behnken design). To the best of our knowledge, this is the first study reporting the fabrication of SLNs from all natural ingredients in the absence of any synthetic surfactants or coatings. The SLNs were prepared by a combined solvent-diffusion and hot homogenization method, with soy lecithin as natural emulsifier (first layer), followed by the subsequent coating with sodium caseinate (second layer) and pectin (third layer), both of which are natural food biopolymers. The adsorption of pectin coating onto caseinate was reinforced by hydrophobic and electrostatic interactions induced by a pH-driven process along with thermal treatment. The innovative nano spray drying technology was further explored to obtain ultra-fine powders of SLNs. Compared to uncoated or single-layer coated SLNs powders, which showed severe aggregation after spray drying, the well-separated particles with spherical shape and smooth surface were obtained for layer-by-layer (LbL) SLNs, which were redispersible into water without variation of dimension, shape and morphology. The SLNs were characterized by Fourier transform infrared and high-performance differential scanning calorimetry for their physical properties. The LbL-coated SLNs based on all natural ingredients have promising features for future applications as drug delivery systems, overcoming the major obstacles in conventional spray drying and redispersing SLNs-based formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. into Solid Lipid Nanoparticles

    Directory of Open Access Journals (Sweden)

    Farhad Jahanfar

    2016-09-01

    Conclusion:The results of the present study indicated that the entrapment of 5-azacytidine into SLNs enhanced its cytotoxicity performance and may pave a way for the future design of a desired dosage form for 5-azacytidine.

  7. A New Application of Lipid Nanoemulsions as Coating Agent, Providing Zero-Order Hydrophilic Drug Release from Tablets

    Directory of Open Access Journals (Sweden)

    Nicolas Anton

    2012-01-01

    Full Text Available The objective of the present investigation was to evaluate potential of nanoemulsions as a coating material for the tablets. The nanoemulsion of size less than 100 nm was prepared using a simple and low-energy spontaneous emulsification method. Conventional tablets containing theophylline as a model hydrophilic drug were prepared. The theophylline tablets were coated with the nanoemulsion using a fluid bed coater. The effect of different levels of the nanoemulsion coating on the theophylline release was evaluated. The theophylline tablets containing different levels of the nanoemulsion coating could be successfully prepared. Interestingly, the coating of tablet with the nanoemulsion resulted in zero-order release of theophylline from the tablets. The noncoated theophylline tablets release the entire drug in less than 2 minutes, whereas nanoemulsion coating delayed the release of theophylline from tablets. This investigation establishes the proof of concept for the potential of nanoemulsions as a coating material for tablets.

  8. How can lipid nanocarriers improve transdermal delivery of olanzapine?

    Science.gov (United States)

    Iqbal, Nimra; Vitorino, Carla; Taylor, Kevin M G

    2017-06-01

    The development of a transdermal nanocarrier drug delivery system with potential for the treatment of psychiatric disorders, such as schizophrenia and bipolar disorder, is described. Lipid nanocarriers (LN), encompassing various solid:liquid lipid compositions were formulated and assessed as potential nanosystems for transdermal delivery of olanzapine. A previously optimized method of hot high pressure homogenization (HPH) was adopted for the production of the LN, which comprised solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Precirol  ® was selected as the solid lipid for progression of studies. SLN exhibited the best performance for transdermal delivery of olanzapine, based on in vitro release and permeation studies, coupled with results from physicochemical characterization of several solid:liquid lipid formulations. Stability tests, performed to give an indication of long-term storage behavior of the formulations, were in good agreement with previous studies for the best choice of solid:liquid lipid ratio. Overall, these findings highlight the SLN-based formulation as promising for the further inclusion in and production of transdermal patches, representing an innovative therapeutic approach.

  9. Inhibitory effects of soluble algae products (SAP) released by Scenedesmus sp. LX1 on its growth and lipid production.

    Science.gov (United States)

    Zhang, Tian-Yuan; Yu, Yin; Wu, Yin-Hu; Hu, Hong-Ying

    2013-10-01

    Soluble algal products (SAP) accumulated in culture medium via water reuse may affect the growth of microalga during the cultivation. Scenedesmus sp. LX1, a freshwater microalga, was used in this study to investigate the effect of SAP on growth and lipid production of microalga. Under the SAP concentrations of 6.4-25.8 mg L(-1), maximum algal density (K) and maximum growth rate (Rmax) of Scenedesmus sp. LX1 were decreased by 50-80% and 35-70% compared with the control group, respectively. The effect of SAP on lipid accumulation of Scenedesmus sp. LX1 was non-significant. According to hydrophilic-hydrophobic and acid-base properties, SAP was fractionized into six fractions. All of the fractions could inhibit the growth of Scenedesmus sp. LX1. Organic bases (HIB, HOB) and hydrophilic acids (HIA) showed the strongest inhibition. HIA could also decrease the lipid content of Scenedesmus sp. LX1 by 59.2%. As the inhibitory effect, SAP should be seriously treated before water reuse. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Development and optimization of oil-filled lipid nanoparticles containing docetaxel conjugates designed to control the drug release rate in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Feng L

    2011-10-01

    Full Text Available Lan Feng1, Huali Wu2, Ping Ma1, Russell J Mumper1,3, S Rahima Benhabbour11Division of Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, UNC Eshelman School of Pharmacy, 2Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, 3UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC, USAAbstract: Three docetaxel (DX lipid conjugates: 2’-lauroyl-docetaxel (C12-DX, 2’-stearoyl-docetaxel (C18-DX, and 2’-behenoyl-docetaxel (C22-DX were synthesized to enhance drug loading, entrapment, and retention in liquid oil-filled lipid nanoparticles (NPs. The three conjugates showed ten-fold higher solubility in the liquid oil phase Miglyol 808 than DX. To further increase the drug entrapment efficiency in NPs, orthogonal design was performed. The optimized formulation was composed of Miglyol 808, Brij 78, and Vitamin E tocopheryl polyethylene glycol succinate (TPGS. The conjugates were successfully entrapped in the reduced-surfactant NPs with entrapment efficiencies of about 50%–60% as measured by gel permeation chromatography (GPC at a final concentration of 0.5 mg/mL. All three conjugates showed 45% initial burst release in 100% mouse plasma. Whereas C12-DX showed another 40% release over the next 8 hours, C18-DX and C22-DX in NPs showed no additional release after the initial burst of drug. All conjugates showed significantly lower cytotoxicity than DX in human DU-145 prostate cancer cells. The half maximal inhibitory concentration values (IC50 of free conjugates and conjugate NPs were comparable except for C22-DX, which was nontoxic in the tested concentration range and showed only vehicle toxicity when entrapped in NPs. In vivo, the total area under the curve (AUC0-∞ values of all DX conjugate NPs were significantly greater than that of Taxotere, demonstrating prolonged retention of drug in the blood. The AUC0-∞ value of DX in Taxotere was 8.3-fold, 358

  11. Release of nanomaterials from solid nanocomposites and consumer exposure assessment - a forward-looking review

    DEFF Research Database (Denmark)

    Mackevica, Aiga; Hansen, Steffen Foss

    2016-01-01

    of the studies report their findings in a format that can be used for exposure assessment under REACH, and most do not include characterization of the released particles. Although inhalation, dermal, and oral exposures can be derived using the guidelines on how to complete consumer exposure assessments under......The European chemical legislation requires manufacturers and importers of chemicals to do consumer exposure assessment when the chemical has certain hazards associated to it (e.g. explosive, carcinogenicity, and hazardous to the aquatic environment), but the question is how this obligation can...... be met in light of the scientific uncertainty and technical challenges related to exposure assessment of nanomaterials. In this paper, we investigate to what extent the information and data in the literature can be used to perform consumer exposure assessment according to the REACH requirements and we...

  12. Systematic Approach for the Formulation and Optimization of Solid Lipid Nanoparticles of Efavirenz by High Pressure Homogenization Using Design of Experiments for Brain Targeting and Enhanced Bioavailability

    Science.gov (United States)

    Gupta, Shweta; Kesarla, Rajesh; Chotai, Narendra; Misra, Ambikanandan

    2017-01-01

    The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting. Solid lipid nanoparticles were prepared by high pressure homogenization technique using a systematic approach of design of experiments (DoE) and evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Particles of average size 108.5 nm having PDI of 0.172 with 64.9% entrapment efficiency were produced. Zeta potential was found to be −21.2 mV and the formulation was found stable. The in-vivo pharmacokinetic studies revealed increased concentration of the drug in brain, as desired, when administered through intranasal route indicating its potential for an attempt towards complete eradication of HIV and cure of HIV-infected patients. PMID:28243600

  13. A new approach to the treatment of recurrent aphthous stomatitis with bioadhesive gels containing cyclosporine A solid lipid nanoparticles: in vivo/in vitro examinations

    Directory of Open Access Journals (Sweden)

    Karavana SY

    2012-11-01

    Full Text Available Sinem Yaprak Karavana,1 Evren Homan Gökçe,1 Seda Rençber,1 Seda Özbal,2 Çetin Pekçetin,2 Pelin Güneri,3 Gökhan Ertan11Department of Pharmaceutical Technology, Faculty of Pharmacy, Ege University, Bornova-Izmir, 2Department of Histology and Embryology, School of Medicine, Dokuz Eylul University, Inciralti, Izmir, 3Department of Oral Diagnosis and Radiology, Faculty of Dentistry, Ege University, Bornova-Izmir, TurkeyAim: To develop a suitable buccal bioadhesive gel formulation containing cyclosporine A solid lipid nanoparticles (CsA SLNs for the treatment of recurrent aphthous stomatitis.Methods: The suitability of the prepared formulations for buccal application was assessed by means of rheological studies, textural profile analysis, and ex vivo drug-release studies. Plastic flows, typical gel-like spectra, and suitable mechanical properties were obtained from prepared formulations. The retention time was explored in in vivo distribution studies and the effect of the gel containing CsA SLNs on the healing of oral mucosal ulceration was investigated in an animal model. In vivo distribution studies are a very important indicator of the retention time of formulations at the application site.Results: Distribution studies showed that 64.76% ± 8.35% of the formulation coded "F8+SLN" remained on the buccal mucosa 6 hours after application. For the second part of the in vivo experiments, 36 rabbits were separated into three groups: the first group was treated with the gel formulation without the active agent; the second group with the gel formulation containing CsA SLNs; and the third group, used as the control group, received no treatment. Wound healing was established by scoring of the rate of wound healing on Days 3, 6, 9, and 12. Histological observations were made on the same days as the scoring studies. The bioadhesive gel formulation that included CsA SLNs increased the rate of mucosal repair significantly.Conclusion: This study has shown

  14. Anti-inflammatory effects and hepatotoxicity of Tripterygium-loaded solid lipid nanoparticles on adjuvant-induced arthritis in rats.

    Science.gov (United States)

    Xue, Mei; Jiang, Zhen-zhou; Wu, Tao; Li, Ji; Zhang, Liang; Zhao, Yan; Li, Xue-jun; Zhang, Lu-Yong; Yang, Shu-yu

    2012-08-15

    Tripterygium wilfordii Hook f. (TWHF) has been demonstrated to have anti-inflammatory, immunosuppressive effects and its clinical use was restricted to some extent due to some toxic effects on the digestive, urogenital, and blood circulatory systems, especially the male reproductive system. In the previous study, we had confirmed that TWHF-loaded solid lipid nanoparticles (SLN) have protective effects on male reproductive toxicity in rats. Anti-inflammatory effects and hepatotoxicity of TWHF-SLN remain to be unidentified. The present study was focused on the anti-inflammatory effect of complete Freund's adjuvant-induced arthritis in rats treated with TWHF-SLN as well as the effects of SLN delivery system on decreasing the hepatotoxicity induced by tripterygium. Sixty-four healthy male rats were randomly divided into eight groups with eight rats each. From day 18 after FCA injection, TWHF-SLN group (120, 60, 30 mg/kg) and TWHF group (120, 60, 30 mg/kg) were administered by oral gavage for 24 consecutive days. The control group was with saline and model control group was without any treatment. The volume of the right hind paws was evaluated at 0, 4, 8, 12, 18, 24, 30, 36 and 42 days post-injection of FCA by a home-made connected device. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TBIL) and albumin (ALB) levels were evaluated by an autoanalyzer. Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) malondialdehyde (MDA) and xanthine oxidase (XOD) levels were determined using commercial kits. The PG level in sera was examined by double antibody sandwich method. Tissue histopathology was evaluated with hematoxylin and eosin (H&E). The results show that TWHF-SLN can significantly reduce rat paw volume at 60 mg/kg (psystem can enhance the anti-inflammatory activity of TWHF, and meanwhile has a protective effect against TWHF

  15. Application of solid-phase extraction coupled with freezing-lipid filtration clean-up for the determination of endocrine-disrupting phenols in fish

    International Nuclear Information System (INIS)

    Ahn, Yun Gyong; Shin, Jeoung Hwa; Kim, Hye-Young; Khim, Jeehyeong; Lee, Mi-Kyoung; Hong, Jongki

    2007-01-01

    An analytical method has been developed for the determination of endocrine-disrupting phenols (eight alkylphenols and bisphenol A) in fish samples. The extraction of nine phenols from fish samples was carried out by ultrasonification. After the extraction, high levels of lipids were removed by freezing-lipid filtration instead of the traditional methods of column chromatography or saponification. During freezing-lipid filtration, about 90% of the lipids were eliminated without any significant loss of phenolic compounds. For further purification, hydrophilic-lipophilic balanced copolymer (HLB) sorbent with a poly(divinylbenzene-co-N-vinylpyrrolidone) phase and Florisil-solid-phase extraction (SPE) cartridges were used to eliminate the remaining interferences. Silyl-derivatization, with N,N'-methyl-(tert-butyldimethylsilyl) trifluoroacetamide (MTBSTFA), was applied to enhance the sensitivity of detection of phenolic compounds. Quantification was performed by gas chromatography/mass spectrometry (GC/MS)-selected ion monitoring (SIM) mode, using deuterium-labeled internal standards. Spiking experiments were carried out to determine the recovery, precision and detection limit of the method. The overall recoveries ranged between 70 and 120%, with relative standard deviations of 3-17% for the entire procedure. The detection limits of the method for the nine phenols ranged from 0.02 to 0.41 ng g -1 . The method provided simultaneous screening and accurate confirmation of each phenol when applied to biological samples

  16. Application of solid-phase extraction coupled with freezing-lipid filtration clean-up for the determination of endocrine-disrupting phenols in fish

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Yun Gyong [Hazardous Substance Research Team, Korea Basic Science Institute, Seoul 136-701 (Korea, Republic of); Department of Civil Environment Engineering, Korea University, Seoul 136-701 (Korea, Republic of); Shin, Jeoung Hwa; Kim, Hye-Young [Hazardous Substance Research Team, Korea Basic Science Institute, Seoul 136-701 (Korea, Republic of); Khim, Jeehyeong [Department of Civil Environment Engineering, Korea University, Seoul 136-701 (Korea, Republic of); Lee, Mi-Kyoung [College of Pharmacy, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Hong, Jongki [College of Pharmacy, Kyung Hee University, Seoul 130-701 (Korea, Republic of)], E-mail: jhong@khu.ac.kr

    2007-11-05

    An analytical method has been developed for the determination of endocrine-disrupting phenols (eight alkylphenols and bisphenol A) in fish samples. The extraction of nine phenols from fish samples was carried out by ultrasonification. After the extraction, high levels of lipids were removed by freezing-lipid filtration instead of the traditional methods of column chromatography or saponification. During freezing-lipid filtration, about 90% of the lipids were eliminated without any significant loss of phenolic compounds. For further purification, hydrophilic-lipophilic balanced copolymer (HLB) sorbent with a poly(divinylbenzene-co-N-vinylpyrrolidone) phase and Florisil-solid-phase extraction (SPE) cartridges were used to eliminate the remaining interferences. Silyl-derivatization, with N,N'-methyl-(tert-butyldimethylsilyl) trifluoroacetamide (MTBSTFA), was applied to enhance the sensitivity of detection of phenolic compounds. Quantification was performed by gas chromatography/mass spectrometry (GC/MS)-selected ion monitoring (SIM) mode, using deuterium-labeled internal standards. Spiking experiments were carried out to determine the recovery, precision and detection limit of the method. The overall recoveries ranged between 70 and 120%, with relative standard deviations of 3-17% for the entire procedure. The detection limits of the method for the nine phenols ranged from 0.02 to 0.41 ng g{sup -1}. The method provided simultaneous screening and accurate confirmation of each phenol when applied to biological samples.

  17. Volatile trace compounds released from municipal solid waste at the transfer stage: Evaluation of environmental impacts and odour pollution.

    Science.gov (United States)

    Zhao, Yan; Lu, Wenjing; Wang, Hongtao

    2015-12-30

    Odour pollution caused by municipal solid waste is a public concern. This study quantitatively evaluated the concentration, environmental impacts, and olfaction of volatile trace compounds released from a waste transfer station. Seventy-six compounds were detected, and ethanol presented the highest releasing rate and ratio of 14.76 kg/d and 12.30 g/t of waste, respectively. Life cycle assessment showed that trichlorofluoromethane and dichlorodifluoromethane accounted for more than 99% of impact potentials to global warming and approximately 70% to human toxicity (non-carcinogenic). The major contributor for both photochemical ozone formation and ecotoxicity was ethanol. A detection threshold method was also used to evaluate odour pollution. Five compounds including methane thiol, hydrogen sulphide, ethanol, dimethyl disulphide, and dimethyl sulphide, with dilution multiples above one, were considered the critical compounds. Methane thiol showed the highest contribution to odour pollution of more than 90%, as indicated by its low threshold. Comparison of the contributions of the compounds to different environmental aspects indicated that typical pollutants varied based on specific evaluation targets and therefore should be comprehensively considered. This study provides important information and scientific methodology to elucidate the impacts of odourant compounds to the environment and odour pollution. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Biowaiver monograph for immediate-release solid oral dosage forms: acetylsalicylic acid.

    Science.gov (United States)

    Dressman, Jennifer B; Nair, Anita; Abrahamsson, Bertil; Barends, Dirk M; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Zimmer, Markus

    2012-08-01

    A biowaiver monograph for acetylsalicylic acid (ASA) is presented. Literature and experimental data indicate that ASA is a highly soluble and highly permeable drug, leading to assignment of this active pharmaceutical ingredient (API) to Class I of the Biopharmaceutics Classification System (BCS). Limited bioequivalence (BE) studies reported in the literature indicate that products that have been tested are bioequivalent. Most of the excipients used in products with a marketing authorization in Europe are not considered to have an impact on gastrointestinal motility or permeability. Furthermore, ASA has a wide therapeutic index. Thus, the risks to the patient that might occur if a nonbioequivalent product were to be incorrectly deemed bioequivalent according to the biowaiver procedure appear to be minimal. As a result, the BCS-based biowaiver procedure can be recommended for approval of new formulations of solid oral dosage forms containing ASA as the only API, including both multisource and reformulated products, under the following conditions: (1) excipients are chosen from those used in ASA products already registered in International Conference on Harmonization and associated countries and (2) the dissolution profiles of the test and the comparator products comply with the BE guidance. Copyright © 2012 Wiley Periodicals, Inc.

  19. Development and optimization of oil-filled lipid nanoparticles containing docetaxel conjugates designed to control the drug release rate in vitro and in vivo.

    Science.gov (United States)

    Feng, Lan; Wu, Huali; Ma, Ping; Mumper, Russell J; Benhabbour, S Rahima

    2011-01-01

    THREE DOCETAXEL (DX) LIPID CONJUGATES: 2'-lauroyl-docetaxel (C12-DX), 2'-stearoyl-docetaxel (C18-DX), and 2'-behenoyl-docetaxel (C22-DX) were synthesized to enhance drug loading, entrapment, and retention in liquid oil-filled lipid nanoparticles (NPs). The three conjugates showed ten-fold higher solubility in the liquid oil phase Miglyol 808 than DX. To further increase the drug entrapment efficiency in NPs, orthogonal design was performed. The optimized formulation was composed of Miglyol 808, Brij 78, and Vitamin E tocopheryl polyethylene glycol succinate (TPGS). The conjugates were successfully entrapped in the reduced-surfactant NPs with entrapment efficiencies of about 50%-60% as measured by gel permeation chromatography (GPC) at a final concentration of 0.5 mg/mL. All three conjugates showed 45% initial burst release in 100% mouse plasma. Whereas C12-DX showed another 40% release over the next 8 hours, C18-DX and C22-DX in NPs showed no additional release after the initial burst of drug. All conjugates showed significantly lower cytotoxicity than DX in human DU-145 prostate cancer cells. The half maximal inhibitory concentration values (IC(50)) of free conjugates and conjugate NPs were comparable except for C22-DX, which was nontoxic in the tested concentration range and showed only vehicle toxicity when entrapped in NPs. In vivo, the total area under the curve (AUC(0-∞)) values of all DX conjugate NPs were significantly greater than that of Taxotere, demonstrating prolonged retention of drug in the blood. The AUC(0-∞) value of DX in Taxotere was 8.3-fold, 358.0-fold, and 454.5-fold lower than that of NP-formulated C12-DX, C18-DX, and C22-DX, respectively. The results of these studies strongly support the idea that the physical/chemical properties of DX conjugates may be fine-tuned to influence the affinity and retention of DX in oil-filled lipid NPs, which leads to very different pharmacokinetic profiles and blood exposure of an otherwise potent chemo

  20. Modulation of butyrate anticancer activity by solid lipid nanoparticle delivery: an in vitro investigation on human breast cancer and leukemia cell lines.

    Science.gov (United States)

    Foglietta, Federica; Serpe, Loredana; Canaparo, Roberto; Vivenza, Nicoletta; Riccio, Giovanna; Imbalzano, Erica; Gasco, Paolo; Zara, Gian Paolo

    2014-01-01

    Histone modification has emerged as a promising approach to cancer therapy. The short-chain fatty acid, butyric acid, a histone deacetylase (HD) inhibitor, has shown anticancer activity. Butyrate transcriptional activation is indeed able to withdraw cancer cells from the cell cycle, leading to programmed cell death. Since butyrate's clinical use is hampered by unfavorable pharmacokinetic and pharmacodynamic properties, delivery systems, such as solid lipid nanoparticles (SLN), have been developed to overcome these constraints. In order to outline the influence of butyrate delivery on its anticancer activity, the effects of butyrate as a free (sodium butyrate, NB) or nanoparticle (cholesteryl butyrate solid lipid nanoparticles, CBSLN) formulation on the growth of different human cancer cell lines, such as the promyelocytic leukemia, HL-60, and the breast cancer, MCF-7 was investigated. A detailed investigation into the mechanism of the induced cytotoxicity was also carried out, with a special focus on the modulation of HD and cyclin-dependent kinase (CDK) mRNA gene expression by real time PCR analysis. In HL-60 cells, CBSLN induced a higher and prolonged expression level of the butyrate target genes at lower concentrations than NB. This led to a significant decrease in cell proliferation, along with considerable apoptosis, cell cycle block in the G0/G1 phase, significant inhibition of total HD activity and overexpression of the p21 protein. Conversely, in MCF-7 cells, CBSLN did not enhance the level of expression of the butyrate target genes, leading to the same anticancer activity as that of NB. Solid lipid nanoparticles were able to improve butyrate anticancer activity in HL-60, but not in MCF-7 cells. This is consistent with difference in properties of the cells under study, such as expression of the TP53 tumor suppressor, or the transporter for short-chain fatty acids, SLC5A8.

  1. Probing the role of ceramide hydroxylation in skin barrier lipid models by 2H solid-state NMR spectroscopy and X-ray powder diffraction.

    Science.gov (United States)

    Kováčik, Andrej; Vogel, Alexander; Adler, Juliane; Pullmannová, Petra; Vávrová, Kateřina; Huster, Daniel

    2018-05-01

    In this work, we studied model stratum corneum lipid mixtures composed of the hydroxylated skin ceramides N-lignoceroyl 6-hydroxysphingosine (Cer[NH]) and α-hydroxylignoceroyl phytosphingosine (Cer[AP]). Two model skin lipid mixtures of the composition Cer[NH] or Cer[AP], N-lignoceroyl sphingosine (Cer[NS]), lignoceric acid (C24:0) and cholesterol in a 0.5:0.5:1:1 molar ratio were compared. Model membranes were investigated by differential scanning calorimetry and 2 H solid-state NMR spectroscopy at temperatures from 25 °C to 80 °C. Each component of the model mixture was specifically deuterated for selective detection by 2 H NMR. Thus, the exact phase composition of the mixture at varying temperatures could be quantified. Moreover, using X-ray powder diffraction we investigated the lamellar phase formation. From the solid-state NMR and DSC studies, we found that both hydroxylated Cer[NH] and Cer[AP] exhibit a similar phase behavior. At physiological skin temperature of 32 °C, the lipids form a crystalline (orthorhombic) phase. With increasing temperature, most of the lipids become fluid and form a liquid-crystalline phase, which converts to the isotropic phase at higher temperatures (65-80 °C). Interestingly, lignoceric acid in the Cer[NH]-containing mixture has a tendency to form two types of fluid phases at 65 °C. This tendency was also observed in Cer[AP]-containing membranes at 80 °C. While Cer[AP]-containing lipid models formed a short periodicity phase featuring a repeat spacing of d = 5.4 nm, in the Cer[NH]-based model skin lipid membranes, the formation of unusual long periodicity phase with a repeat spacing of d = 10.7 nm was observed. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy as an Analytical Method to Investigate the Secondary Structure of a Model Protein Embedded in Solid Lipid Matrices.

    Science.gov (United States)

    Zeeshan, Farrukh; Tabbassum, Misbah; Jorgensen, Lene; Medlicott, Natalie J

    2018-02-01

    Protein drugs may encounter conformational perturbations during the formulation processing of lipid-based solid dosage forms. In aqueous protein solutions, attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy can investigate these conformational changes following the subtraction of spectral interference of solvent with protein amide I bands. However, in solid dosage forms, the possible spectral contribution of lipid carriers to protein amide I band may be an obstacle to determine conformational alterations. The objective of this study was to develop an ATR FT-IR spectroscopic method for the analysis of protein secondary structure embedded in solid lipid matrices. Bovine serum albumin (BSA) was chosen as a model protein, while Precirol AT05 (glycerol palmitostearate, melting point 58 ℃) was employed as the model lipid matrix. Bovine serum albumin was incorporated into lipid using physical mixing, melting and mixing, or wet granulation mixing methods. Attenuated total reflection FT-IR spectroscopy and size exclusion chromatography (SEC) were performed for the analysis of BSA secondary structure and its dissolution in aqueous media, respectively. The results showed significant interference of Precirol ATO5 with BSA amide I band which was subtracted up to 90% w/w lipid content to analyze BSA secondary structure. In addition, ATR FT-IR spectroscopy also detected thermally denatured BSA solid alone and in the presence of lipid matrix indicating its suitability for the detection of denatured protein solids in lipid matrices. Despite being in the solid state, conformational changes occurred to BSA upon incorporation into solid lipid matrices. However, the extent of these conformational alterations was found to be dependent on the mixing method employed as indicated by area overlap calculations. For instance, the melting and mixing method imparted negligible effect on BSA secondary structure, whereas the wet granulation mixing method promoted

  3. Reconciling Differences between Lipid Transfer in Free-Standing and Solid Supported Membranes: A Time-Resolved Small-Angle Neutron Scattering Study.

    Science.gov (United States)

    Wah, Benny; Breidigan, Jeffrey M; Adams, Joseph; Horbal, Piotr; Garg, Sumit; Porcar, Lionel; Perez-Salas, Ursula

    2017-04-11

    Maintaining compositional lipid gradients across membranes in animal cells is essential to biological function, but what is the energetic cost to maintain these differences? It has long been recognized that studying the passive movement of lipids in membranes can provide insight into this toll. Confusingly the reported values of inter- and, particularly, intra-lipid transport rates of lipids in membranes show significant differences. To overcome this difficulty, biases introduced by experimental approaches have to be identified. The present study addresses the difference in the reported intramembrane transport rates of dimyristoylphosphatidylcholine (DMPC) on flat solid supports (fast flipping) and in curved free-standing membranes (slow flipping). Two possible scenarios are potentially at play: one is the difference in curvature of the membranes studied and the other the presence (or not) of the support. Using DMPC vesicles and DMPC supported membranes on silica nanoparticles of different radii, we found that an increase in curvature (from a diameter of 30 nm to a diameter of 100 nm) does not change the rates significantly, differing only by factors of order ∼1. Additionally, we found that the exchange rates of DMPC in supported membranes are similar to the ones in vesicles. And as previously reported, we found that the activation energies for exchange on free-standing and supported membranes are similar (84 and 78 kJ/mol, respectively). However, DMPC's flip-flop rates increase significantly when in a supported membrane, surpassing the exchange rates and no longer limiting the exchange process. Although the presence of holes or cracks in supported membranes explains the occurrence of fast lipid flip-flop in many studies, in defect-free supported membranes we find that fast flip-flop is driven by the surface's induced disorder of the bilayer's acyl chain packing as evidenced from their broad melting temperature behavior.

  4. Probing the mechanisms of drug release from amorphous solid dispersions in medium-soluble and medium-insoluble carriers.

    Science.gov (United States)

    Sun, Dajun D; Lee, Ping I

    2015-08-10

    The objective of the current study is to mechanistically differentiate the dissolution and supersaturation behaviors of amorphous drugs from amorphous solid dispersions (ASDs) based on medium-soluble versus medium-insoluble carriers under nonsink dissolution conditions through a direct head-to-head comparison. ASDs of indomethacin (IND) were prepared in several polymers which exhibit different solubility behaviors in acidic (pH1.2) and basic (pH7.4) dissolution media. The selected polymers range from water-soluble (e.g., PVP and Soluplus) and water-insoluble (e.g., ethylcellulose and Eudragit RL PO) to those only soluble in an acidic or basic dissolution medium (e.g., Eudragit E100, Eudragit L100, and HPMCAS). At 20wt.% drug loading, DSC and powder XRD analysis confirmed that the majority of incorporated IND was present in an amorphous state. Our nonsink dissolution results confirm that whether the carrier matrix is medium soluble determines the release mechanism of amorphous drugs from ASD systems which has a direct impact on the rate of supersaturation generation, thus in turn affecting the evolution of supersaturation in amorphous systems. For example, under nonsink dissolution conditions, the release of amorphous IND from medium-soluble carriers is governed by a dissolution-controlled mechanism leading to an initial surge of supersaturation followed by a sharp decline in drug concentration due to rapid nucleation and crystallization. In contrast, the dissolution of IND ASD from medium-insoluble carriers is more gradual as drug release is regulated by a diffusion-controlled mechanism by which drug supersaturation is built up gradually and sustained over an extended period of time without any apparent decline. Since several tested carrier polymers can be switched from soluble to insoluble by simply changing the pH of the dissolution medium, the results obtained here provide unequivocal evidence of the proposed transition of kinetic solubility profiles from the

  5. Biosynthesis of silver nanoparticle and its application in cell wall disruption to release carbohydrate and lipid from C. vulgaris for biofuel production

    Directory of Open Access Journals (Sweden)

    Sirajunnisa Abdul Razack

    2016-09-01

    Full Text Available Microalgae are the fledging feedstocks yielding raw materials for the production of third generation biofuel. Assorted and conventional cell wall disruption techniques were helpful in extracting lipids and carbohydrates, nevertheless the disadvantages have led the biotechnologists to explore new process to lyse cell wall in a faster and an economical manner. Silver nanoparticles have the ability to break the cell wall of microalgae and release biomolecules effectively. Green synthesis of silver nanoparticles was performed using a novel bacterial isolate of Bacillus subtilis. Characterisation of nanosilver and its effect on cell wall lysis of microalgae were extensively analysed. Cell wall damage was confirmed by lactate dehydrogenase assay and visually by SEM analysis. This first piece of research work on direct use of nanoparticles for cell wall lysis would potentially be advantageous over its conventional approaches and a greener, cost effective and non laborious method for the production of biodiesel.

  6. Effects of immediate-release niacin and dietary fatty acids on acute insulin and lipid status in individuals with metabolic syndrome.

    Science.gov (United States)

    Montserrat-de la Paz, Sergio; Lopez, Sergio; Bermudez, Beatriz; Guerrero, Juan M; Abia, Rocio; Muriana, Francisco Jg

    2018-04-01

    The nature of dietary fats profoundly affects postprandial hypertriglyceridemia and glucose homeostasis. Niacin is a potent lipid-lowering agent. However, limited data exist on postprandial triglycerides and glycemic control following co-administration of high-fat meals with a single dose of niacin in subjects with metabolic syndrome (MetS). The aim of the study was to explore whether a fat challenge containing predominantly saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or MUFAs plus omega-3 long-chain polyunsaturated (LCPUFAs) fatty acids together with a single dose of immediate-release niacin have a relevant role in postprandial insulin and lipid status in subjects with MetS. In a randomized crossover within-subject design, 16 men with MetS were given a single dose of immediate-release niacin (2 g) and ∼15 cal kg -1 body weight meals containing either SFAs, MUFAs, MUFAs plus omega-3 LCPUFAs or no fat. At baseline and hourly over 6 h, plasma glucose, insulin, C-peptide, triglycerides, free fatty acids (FFAs), total cholesterol, and both high- and low-density lipoprotein cholesterol were assessed. Co-administered with niacin, high-fat meals significantly increased the postprandial concentrations of glucose, insulin, C-peptide, triglycerides, FFAs and postprandial indices of β-cell function. However, postprandial indices of insulin sensitivity were significantly decreased. These effects were significantly attenuated with MUFAs or MUFAs plus omega-3 LCPUFAs when compared with SFAs. In the setting of niacin co-administration and compared to dietary SFAs, MUFAs limit the postprandial insulin, triglyceride and FFA excursions, and improve postprandial glucose homeostasis in MetS. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  7. Does the commonly used pH-stat method with back titration really quantify the enzymatic digestibility of lipid drug delivery systems? A case study on solid lipid nanoparticles (SLN).

    Science.gov (United States)

    Heider, Martha; Hause, Gerd; Mäder, Karsten

    2016-12-01

    Enzymatic digestion of lipid drug carriers is very important. Commonly, pancreatin induced formation of fatty acids is monitored by the pH-stat method, which provides a fast, but unspecific readout. However, according to the literature, the pKa values of long chain fatty acids are strongly dependent on the local environment and might vary between 4.2 and 10.15. The high pKa values would lead to an incomplete detection of the lipid digestion and false results. In order to investigate these issues in more detail, we produced cetyl palmitate solid lipid nanoparticles (CP-SLN) stabilized with poloxamer 188 or polysorbate 80. The digestion of CP-SLN was investigated by two different and independent readouts. A HPTLC assay was used in addition to the pH-stat method (with or without back titration). An incomplete digestion of CP-SLN was observed with all methods. Partial digestion of polysorbate 80 contributed to the formation of fatty acids. Depending on the investigated system and the experimental conditions (FaSSIF or FeSSIF) the results of both readout methods were comparable or not. For example, in FeSSIF conditions, the values detected by HPTLC were roughly twice as high as the pH-stat results. Our findings on solid lipids agree with data from Helbig et al. on lipid emulsions, where a gas chromatography method detected much higher values than the pH-stat assay (Food Hydrocoll. 28 (2012) 10-19). The results of our pH-stat experiments with back titration at different pH values showed increased values for fatty acids from pH 7.5 to pH 10. The values obtained by back titration at high pH values (pH 9 or higher) did exceed the digestion values measured by HPTLC. Therefore, we conclude that the pH-stat method might give the same results as more specific reference methods, but it might also both under- (without back titration) or overestimate (with back titration) the enzymatic digestion of lipid drug delivery systems. A further outcome of our study was the proof that

  8. Crystalline Ethylene Oxide and Propylene Oxide Triblock Copolymer Solid Dispersion Enhance Solubility, Stability and Promoting Time- Controllable Release of Curcumin.

    Science.gov (United States)

    Alves, Thais F R; das Neves Lopes, Franciely C C; Rebelo, Marcia A; Souza, Juliana F; da Silva Pontes, Katiusca; Santos, Carolina; Severino, Patricia; Junior, Jose M O; Komatsu, Daniel; Chaud, Marco V

    2018-01-01

    The design and development of an effective medicine are, however, often faced with a number of challenges. One of them is the close relationship of drug's bioavailability with solubility, dissolution rate and permeability. The use of curcumin's (CUR) therapeutic potential is limited by its poor water solubility and low chemical stability. The purpose was to evaluate the effect of polymer and solid dispersion (SD) preparation techniques to enhance the aqueous solubility, dissolution rate and stability of the CUR. The recent patents on curcumin SD were reported as (i) curcumin with polyvinylpyrrolidone (CN20071 32500 20071214, WO2006022012 and CN20151414227 20150715), (ii) curcumin-zinc/polyvinylpyrrolidone (CN20151414227 20150715), (iii) curcumin-poloxamer 188 (CN2008171177 20080605), (iv) curcumin SD prepared by melting method (CN20161626746-20160801). SD obtained by co-preciptation or microwave fusion and the physical mixture of CUR with Poloxamer-407 (P-407), Hydroxypropylmetylcellulose-K4M (HPMC K4M) and Polyvinylpyrrolidone-K30 (PVP-K30) were prepared at the ratios of 1:2; 1:1 and 2:1. The samples were evaluated by solubility, stability, dissolution rate and characterized by SEM, PXRD, DSC and FTIR. The solubility, stability (pH 7.0) and dissolution rate were significantly greater for SD (CUR:P-407 1:2). The PXRD,SEM and DSC indicated a change in the crystalline state of CUR. The enhancement of solubility was dependent on a combination of factors including the weight ratio, preparation techniques and carrier properties. The drug release data fitted well with the Weibull equation, indicating that the drug release was controlled by diffusion, polymer relaxation and erosion occurring simultaneously. Thus, these SDs, specifically CUR:P-407 1:2 w/w, can overcome the barriers of poor bioavailability to reap many beneficial properties. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Interaction analysis of chimeric metal-binding green fluorescent protein and artificial solid-supported lipid membrane by quartz crystal microbalance and atomic force microscopy

    International Nuclear Information System (INIS)

    Prachayasittikul, Virapong; Na Ayudhya, Chartchalerm Isarankura; Hilterhaus, Lutz; Hinz, Andreas; Tantimongcolwat, Tanawut; Galla, Hans-Joachim

    2005-01-01

    Non-specific adsorption and specific interaction between a chimeric green fluorescent protein (GFP) carrying metal-binding region and the immobilized zinc ions on artificial solid-supported lipid membranes was investigated using the quartz crystal microbalance technique and the atomic force microscopy (AFM). Supported lipid bilayer, composed of octanethiol and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-sn-glycero-3-[N- (5-amino-1-carboxypentyl iminodiacetic acid)succinyl] (NTA-DOGS)-Zn 2+ , was formed on the gold electrode of quartz resonator (5 MHz). Binding of the chimeric GFP to zinc ions resulted in a rapid decrease of resonance frequency. Reversibility of the process was demonstrated via the removal of metal ions by EDTA. Nanoscale structural orientation of the chimeric GFP on the membrane was imaged by AFM. Association constant of the specific binding to metal ions was 2- to 3-fold higher than that of the non-specific adsorption, which was caused by the fluidization effect of the metal-chelating lipid molecules as well as the steric hindrance effect. This infers a possibility for a further development of biofunctionalized membrane. However, maximization is needed in order to attain closer advancement to a membrane-based sensor device

  10. Multidimensional oriented solid-state NMR experiments enable the sequential assignment of uniformly 15N labeled integral membrane proteins in magnetically aligned lipid bilayers

    International Nuclear Information System (INIS)

    Mote, Kaustubh R.; Gopinath, T.; Traaseth, Nathaniel J.; Kitchen, Jason; Gor’kov, Peter L.; Brey, William W.; Veglia, Gianluigi

    2011-01-01

    Oriented solid-state NMR is the most direct methodology to obtain the orientation of membrane proteins with respect to the lipid bilayer. The method consists of measuring 1 H- 15 N dipolar couplings (DC) and 15 N anisotropic chemical shifts (CSA) for membrane proteins that are uniformly aligned with respect to the membrane bilayer. A significant advantage of this approach is that tilt and azimuthal (rotational) angles of the protein domains can be directly derived from analytical expression of DC and CSA values, or, alternatively, obtained by refining protein structures using these values as harmonic restraints in simulated annealing calculations. The Achilles’ heel of this approach is the lack of suitable experiments for sequential assignment of the amide resonances. In this Article, we present a new pulse sequence that integrates proton driven spin diffusion (PDSD) with sensitivity-enhanced PISEMA in a 3D experiment ([ 1 H, 15 N]-SE-PISEMA-PDSD). The incorporation of 2D 15 N/ 15 N spin diffusion experiments into this new 3D experiment leads to the complete and unambiguous assignment of the 15 N resonances. The feasibility of this approach is demonstrated for the membrane protein sarcolipin reconstituted in magnetically aligned lipid bicelles. Taken with low electric field probe technology, this approach will propel the determination of sequential assignment as well as structure and topology of larger integral membrane proteins in aligned lipid bilayers.

  11. Multidimensional oriented solid-state NMR experiments enable the sequential assignment of uniformly 15N labeled integral membrane proteins in magnetically aligned lipid bilayers.

    Science.gov (United States)

    Mote, Kaustubh R; Gopinath, T; Traaseth, Nathaniel J; Kitchen, Jason; Gor'kov, Peter L; Brey, William W; Veglia, Gianluigi

    2011-11-01

    Oriented solid-state NMR is the most direct methodology to obtain the orientation of membrane proteins with respect to the lipid bilayer. The method consists of measuring (1)H-(15)N dipolar couplings (DC) and (15)N anisotropic chemical shifts (CSA) for membrane proteins that are uniformly aligned with respect to the membrane bilayer. A significant advantage of this approach is that tilt and azimuthal (rotational) angles of the protein domains can be directly derived from analytical expression of DC and CSA values, or, alternatively, obtained by refining protein structures using these values as harmonic restraints in simulated annealing calculations. The Achilles' heel of this approach is the lack of suitable experiments for sequential assignment of the amide resonances. In this Article, we present a new pulse sequence that integrates proton driven spin diffusion (PDSD) with sensitivity-enhanced PISEMA in a 3D experiment ([(1)H,(15)N]-SE-PISEMA-PDSD). The incorporation of 2D (15)N/(15)N spin diffusion experiments into this new 3D experiment leads to the complete and unambiguous assignment of the (15)N resonances. The feasibility of this approach is demonstrated for the membrane protein sarcolipin reconstituted in magnetically aligned lipid bicelles. Taken with low electric field probe technology, this approach will propel the determination of sequential assignment as well as structure and topology of larger integral membrane proteins in aligned lipid bilayers. © Springer Science+Business Media B.V. 2011

  12. The use of quasi-isothermal modulated temperature differential scanning calorimetry for the characterization of slow crystallization processes in lipid-based solid self-emulsifying systems.

    Science.gov (United States)

    Otun, Sarah O; Meehan, Elizabeth; Qi, Sheng; Craig, Duncan Q M

    2015-04-01

    Slow or incomplete crystallization may be a significant manufacturing issue for solid lipid-based dosage forms, yet little information is available on this phenomenon. In this investigation we suggest a novel means by which slow solidification may be monitored in Gelucire 44/14 using quasi-isothermal modulated temperature DSC (QiMTDSC). Conventional linear heating and cooling DSC methods were employed, along with hot stage microscopy (HSM), for basic thermal profiling of Gelucire 44/14. QiMTDSC experiments were performed on cooling from the melt, using a range of incremental decreases in temperature and isothermal measurement periods. DSC and HSM highlighted the main (primary) crystallization transition; solid fat content analysis and kinetic analysis were used to profile the solidification process. The heat capacity profile from QiMTDSC indicated that after an initial energetic primary crystallisation, the lipid underwent a slower period of crystallization which continued to manifest at much lower temperatures than indicated by standard DSC. We present evidence that Gelucire 44/14 undergoes an initial crystallization followed by a secondary, slower process. QIMTDSC appears to be a promising tool in the investigation of this secondary crystallization process.

  13. Uniform isotope labeling of a eukaryotic seven-transmembrane helical protein in yeast enables high-resolution solid-state NMR studies in the lipid environment

    International Nuclear Information System (INIS)

    Fan Ying; Shi Lichi; Ladizhansky, Vladimir; Brown, Leonid S.

    2011-01-01

    Overexpression of isotope-labeled multi-spanning eukaryotic membrane proteins for structural NMR studies is often challenging. On the one hand, difficulties with achieving proper folding, membrane insertion, and native-like post-translational modifications frequently disqualify bacterial expression systems. On the other hand, eukaryotic cell cultures can be prohibitively expensive. One of the viable alternatives, successfully used for producing proteins for solution NMR studies, is yeast expression systems, particularly Pichia pastoris. We report on successful implementation and optimization of isotope labeling protocols, previously used for soluble secreted proteins, to produce homogeneous samples of a eukaryotic seven-transmembrane helical protein, rhodopsin from Leptosphaeria maculans. Even in shake-flask cultures, yields exceeded 5 mg of purified uniformly 13 C, 15 N-labeled protein per liter of culture. The protein was stable (at least several weeks at 5°C) and functionally active upon reconstitution into lipid membranes at high protein-to-lipid ratio required for solid-state NMR. The samples gave high-resolution 13 C and 15 N solid-state magic angle spinning NMR spectra, amenable to a detailed structural analysis. We believe that similar protocols can be adopted for challenging mammalian targets, which often resist characterization by other structural methods.

  14. Dual-layered nanogel-coated hollow lipid/polypeptide conjugate assemblies for potential pH-triggered intracellular drug release.

    Directory of Open Access Journals (Sweden)

    Wen-Hsuan Chiang

    Full Text Available To achieve effective intracellular anticancer drug delivery, the polymeric vesicles supplemented with the pH-responsive outlayered gels as a delivery system of doxorubicin (DOX were developed from self-assembly of the lipid/polypeptide adduct, distearin grafted poly(γ-glutamic acid (poly(γ-GA, followed by sequential deposition of chitosan and poly(γ-GA-co-γ-glutamyl oxysuccinimide-g-monomethoxy poly(ethylene glycol in combination with in situ covalent cross-linking on assembly surfaces. The resultant gel-caged polymeric vesicles (GCPVs showed superior performance in regulating drug release in response to the external pH change. Under typical physiological conditions (pH 7.4 and 37 °C at which the γ-GA/DOX ionic pairings remained mostly undisturbed, the dense outlayered gels of GCPVs significantly reduced the premature leakage of the uncomplexed payload. With the environmental pH being reduced from pH 7.4 to 4.7, the drug liberation was appreciably promoted by the massive disruption of the ionic γ-GA/DOX complexes along with the significant swelling of nanogel layers upon the increased protonation of chitosan chain segments. After being internalized by HeLa cells via endocytosis, GCPVs exhibited cytotoxic effect comparable to free DOX achieved by rapidly releasing the payload in intracellular acidic endosomes and lysosomes. This strongly implies the great promise of such unique GCPVs as an intracellular drug delivery carrier for potential anticancer treatment.

  15. Solid lipid nanoparticles for hydrophilic biotech drugs: optimization and cell viability studies (Caco-2 & HEPG-2 cell lines)

    Czech Academy of Sciences Publication Activity Database

    Severino, P.; Andreani, T.; Jäger, Alessandro; Chaud, M. V.; Santana, M. H. A.; Silva, A. M.; Souto, E. B.

    2014-01-01

    Roč. 81, 23 June (2014), s. 28-34 ISSN 0223-5234 R&D Projects: GA ČR GAP208/10/1600 Institutional support: RVO:61389013 Keywords : lipid nanoparticles * double emulsion * hydrophilic biotech drugs Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.447, year: 2014

  16. Lipid Dynamics Studied by Calculation of 31P Solid-State NMR Spectra Using Ensembles from Molecular Dynamics Simulations

    DEFF Research Database (Denmark)

    Hansen, Sara Krogh; Vestergaard, Mikkel; Thøgersen, Lea

    2014-01-01

    , for example, order parameters. Therefore, valuable insight into the dynamics of biomolecules may be achieved by the present method. We have applied this method to study the dynamics of lipid bilayers containing the antimicrobial peptide alamethicin, and we show that the calculated 31P spectra obtained...

  17. Optimization of total vaporization solid-phase microextraction (TV-SPME) for the determination of lipid profiles of Phormia regina, a forensically important blow fly species.

    Science.gov (United States)

    Kranz, William; Carroll, Clinton; Dixon, Darren; Picard, Christine; Goodpaster, John

    2017-11-01

    A new method has been developed for the determination of fatty acids, sterols, and other lipids which naturally occur within pupae of the blow fly Phormia regina. The method relies upon liquid extraction in non-polar solvent, followed by derivatization using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) w/ 1% trimethylchlorsilane (TMCS) carried out inside the sample vial. The analysis is facilitated by total vaporization solid-phase microextraction (TV-SPME), with gas chromatography-mass spectrometry (GC-MS) serving as the instrumentation for analysis. The TV-SPME delivery technique is approximately a factor of five more sensitive than traditional liquid injection, which may alleviate the need for rotary evaporation, reconstitution, collection of high performance liquid chromatography fractions, and many of the other pre-concentration steps that are commonplace in the current literature. Furthermore, the ability to derivatize the liquid extract in a single easy step while increasing sensitivity represents an improvement over current derivatization methods. The most common lipids identified in fly pupae were various saturated and unsaturated fatty acids ranging from lauric acid (12:0) to arachinoic acid (20:4), as well as cholesterol. The concentrations of myristic acid (14:0), palmitelaidic acid (16:2), and palmitoleic acid (16:1) were the most reliable indicators of the age of the pupae. Graphical abstract Blow fly pupae were extracted prior to emerging as adults. The extracts were analyzed via total vaporization solid-phase microextraction (TV-SPME), revealing a complex mixture of lipids that could be associated with the age of the insect. This information may assist in determining a post-mortum interval (PMI) in a death investigation.

  18. Cytokine Release Assays as Tests for Exposure to Leishmania, and for Confirming Cure from Leishmaniasis, in Solid Organ Transplant Recipients.

    Directory of Open Access Journals (Sweden)

    Eugenia Carrillo

    Full Text Available Spain has one of the world's largest pools of organ donors and is a global leader in terms of the number of transplants it performs. The current outbreak of leishmaniasis in Fuenlabrada (in the southwest of the region of Madrid, Spain has involved 600 clinical cases since late 2009 (prevalence 0.2%. It may therefore be wise to monitor the town's transplanted population for Leishmania infantum; its members are immunosuppressed and at greater risk of infection and relapse following treatment. The present work examines the use of cytokine release assays to determine the prevalence of Leishmania infection in this population, and to confirm recovery following treatment for visceral leishmaniasis (VL. The humoral and cellular immune responses to L. infantum were characterized in 63 solid organ transplant (SOT recipients from Fuenlabrada, 57 of whom reported no previous episode of VL (NVL subjects, and six of whom had been cured of VL (CVL subjects. Seventeen subjects (12 NVL and 5 CVL showed a patent lymphoproliferative response to soluble Leishmania antigen (SLA. Stimulation of peripheral blood mononuclear cell cultures and of whole blood with SLA led to the production of different combinations of cytokines that might serve to confirm Leishmania infection or recovery from VL and help prevent cured patients from relapsing into this serious condition.

  19. Determination of phthalates released from paper packaging materials by solid-phase extraction-high-performance liquid chromatography.

    Science.gov (United States)

    Gao, Xin; Yang, Bofeng; Tang, Zhixu; Luo, Xin; Wang, Fengmei; Xu, Hui; Cai, Xue

    2014-01-01

    A solid phase extraction (SPE) high-performance liquid chromatography (HPLC) method was developed for the simultaneous determination of 10 phthalic acid esters (dimethyl phthalate, diethyl phthalate, dipropyl phthalate, benzylbutyl phthalate, diisobutyl phthalate, dicyclohexyl phthalate, diamyl phthalate, di-n-hexyl phthalate, di-n-octyl phthalate and di-2-ethylhexyl phthalate) released from food paper packaging materials. The use of distilled water, 3% acetic acid (w/v), 10% ethanol (v/v) and 95% ethanol (v/v) instead of the different types of food simulated the migration of 10 phthalic acid esters from food paper packaging materials; the phthalic acid esters in four food simulants were enriched and purified by a C18 SPE column and nitrogen blowing, and quantified by HPLC with a diode array detector. The chromatographic conditions and extraction conditions were optimized and all 10 of the phthalate acid esters had a maximum absorbance at 224 nm. The method showed limitations of detection in the range of 6.0-23.8 ng/mL the correlation coefficients were greater than 0.9999 in all cases, recovery values ranged between 71.27 and 106.97% at spiking levels of 30, 60 and 90 ng/mL and relative standard deviation values ranged from 0.86 to 8.00%. The method was considered to be simple, fast and reliable for a study on the migration of these 10 phthalic acid esters from food paper packaging materials into food.

  20. Development and evaluation of resveratrol, Vitamin E, and epigallocatechin gallate loaded lipid nanoparticles for skin care applications.

    Science.gov (United States)

    Chen, Jin; Wei, Ning; Lopez-Garcia, Maria; Ambrose, Dianna; Lee, Jason; Annelin, Colin; Peterson, Teresa

    2017-08-01

    Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been studied as potential carriers for both dermal and transdermal drug delivery. SLN contain lipid droplets that are fully crystallized and have a highly-ordered crystalline structure. NLC are modified SLN in which the lipid phase contains both solid and liquid lipids at room temperature. SLN and NLC are thought to combine the advantages of polymeric particles, liposomes and emulsions. Therefore they provide high encapsulation percentages, better protection for incorporated actives and allow for control of desired release profile. In this work, Resveratrol, Vitamin E (VE), and Epigallocatechin Gallate (EGCG) all potent antioxidants known to provide protection to the skin, were formulated into lipid nanoparticles. Several different formulations were successfully developed and demonstrated high uniformity and stability. Both resveratrol and VE lipid nanoparticles provided effective protection of actives against UV induced degradation. However, lipid nanoparticles did not show protection from UV degradation for EGCG in this work. An active release study exhibited a sustained release of resveratrol over 70% after 24h. Skin penetration studies showed that lipid nanoparticles directionally improved the penetration of resveratrol through the stratum corneum. Our findings suggest that lipid nanoparticles are promising viable carriers for the delivery of resveratrol and VE to provide longlasting antioxidant benefits to the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Determination of structural topology of a membrane protein in lipid bilayers using polarization optimized experiments (POE) for static and MAS solid state NMR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Mote, Kaustubh R. [University of Minnesota, Department of Chemistry (United States); Gopinath, T. [University of Minnesota, Department of Biochemistry, Molecular Biology and Biophysics (United States); Veglia, Gianluigi, E-mail: vegli001@umn.edu [University of Minnesota, Department of Chemistry (United States)

    2013-10-15

    The low sensitivity inherent to both the static and magic angle spinning techniques of solid-state NMR (ssNMR) spectroscopy has thus far limited the routine application of multidimensional experiments to determine the structure of membrane proteins in lipid bilayers. Here, we demonstrate the advantage of using a recently developed class of experiments, polarization optimized experiments, for both static and MAS spectroscopy to achieve higher sensitivity and substantial time-savings for 2D and 3D experiments. We used sarcolipin, a single pass membrane protein, reconstituted in oriented bicelles (for oriented ssNMR) and multilamellar vesicles (for MAS ssNMR) as a benchmark. The restraints derived by these experiments are then combined into a hybrid energy function to allow simultaneous determination of structure and topology. The resulting structural ensemble converged to a helical conformation with a backbone RMSD {approx}0.44 A, a tilt angle of 24 Degree-Sign {+-} 1 Degree-Sign , and an azimuthal angle of 55 Degree-Sign {+-} 6 Degree-Sign . This work represents a crucial first step toward obtaining high-resolution structures of large membrane proteins using combined multidimensional oriented solid-state NMR and magic angle spinning solid-state NMR.

  2. Nanoparticles of lipid monolayer shell and biodegradable polymer core for controlled release of paclitaxel: effects of surfactants on particles size, characteristics and in vitro performance.

    Science.gov (United States)

    Liu, Yutao; Pan, Jie; Feng, Si-Shen

    2010-08-16

    This work developed a system of nanoparticles of lipid monolayer shell and biodegradable polymer core for controlled release of anticancer drugs with paclitaxel as a model drug, in which the emphasis was given to the effects of the surfactant type and the optimization of the emulsifier amount used in the single emulsion solvent evaporation/extraction process for the nanoparticle preparation on the particle size, characters and in vitro performance. The drug loaded nanoparticles were characterized by laser light scattering (LLS) for size and size distribution, field-emission scanning electron microscopy (FESEM) for surface morphology, X-ray photoelectron spectroscopy (XPS) for surface chemistry, zetasizer for surface charge, and high performance liquid chromatography (HPLC) for drug encapsulation efficiency and in vitro drug release kinetics. MCF-7 breast cancer cells were employed to evaluate the cellular uptake and cytotoxicity. It was found that phospholipids of short chains such as 1,2-dilauroylphosphatidylocholine (DLPC) have great advantages over the traditional emulsifier poly(vinyl alcohol) (PVA), which is used most often in the literature, in preparation of nanoparticles of biodegradable polymers such as poly(D,L-lactide-co-glycolide) (PLGA) for desired particle size, character and in vitro cellular uptake and cytotoxicity. After incubation with MCF-7 cells at 0.250 mg/ml NP concentration, the coumarin-6 loaded PLGA NPs of DLPC shell showed more effective cellular uptake versus those of PVA shell. The analysis of IC(50), i.e. the drug concentration at which 50% of the cells are killed, demonstrated that our DLPC shell PLGA core NP formulation of paclitaxel could be 5.88-, 5.72-, 7.27-fold effective than the commercial formulation Taxol after 24, 48, 72h treatment, respectively. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  3. Characterization of a Cyclic Nucleotide-Activated K+ Channel and its Lipid Environment by Using Solid-State NMR Spectroscopy

    NARCIS (Netherlands)

    Cukkemane, A.A.; Baldus, M.

    2013-01-01

    Voltage-gated ion channels are large tetrameric multidomain membrane proteins that play crucial roles in various cellular transduction pathways. Because of their large size and domain-related mobility, structural characterization has proved challenging. We analyzed high-resolution solid-state NMR

  4. 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.

  5. Solid-State Nuclear Magnetic Resonance Investigation of the Structural Topology and Lipid Interactions of a Viral Fusion Protein Chimera Containing the Fusion Peptide and Transmembrane Domain.

    Science.gov (United States)

    Yao, Hongwei; Lee, Myungwoon; Liao, Shu-Yu; Hong, Mei

    2016-12-13

    The fusion peptide (FP) and transmembrane domain (TMD) of viral fusion proteins play important roles during virus-cell membrane fusion, by inducing membrane curvature and transient dehydration. The structure of the water-soluble ectodomain of viral fusion proteins has been extensively studied crystallographically, but the structures of the FP and TMD bound to phospholipid membranes are not well understood. We recently investigated the conformations and lipid interactions of the separate FP and TMD peptides of parainfluenza virus 5 (PIV5) fusion protein F using solid-state nuclear magnetic resonance. These studies provide structural information about the two domains when they are spatially well separated in the fusion process. To investigate how these two domains are structured relative to each other in the postfusion state, when the ectodomain forms a six-helix bundle that is thought to force the FP and TMD together in the membrane, we have now expressed and purified a chimera of the FP and TMD, connected by a Gly-Lys linker, and measured the chemical shifts and interdomain contacts of the protein in several lipid membranes. The FP-TMD chimera exhibits α-helical chemical shifts in all the membranes examined and does not cause strong curvature of lamellar membranes or membranes with negative spontaneous curvature. These properties differ qualitatively from those of the separate peptides, indicating that the FP and TMD interact with each other in the lipid membrane. However, no 13 C- 13 C cross peaks are observed in two-dimensional correlation spectra, suggesting that the two helices are not tightly associated. These results suggest that the ectodomain six-helix bundle does not propagate into the membrane to the two hydrophobic termini. However, the loosely associated FP and TMD helices are found to generate significant negative Gaussian curvature to membranes that possess spontaneous positive curvature, consistent with the notion that the FP-TMD assembly may

  6. Total phenolic contents, antioxidant activities, and lipid fractions from berry pomaces obtained by solid-state fermentation of two Sambucus species with Aspergillus niger.

    Science.gov (United States)

    Dulf, Francisc Vasile; Vodnar, Dan Cristian; Dulf, Eva-Henrietta; Toşa, Monica Ioana

    2015-04-08

    The aim of this study was to investigate the effect of solid-state fermentation (SSF) by Aspergillus niger on phenolic contents and antioxidant activity in Sambucus nigra L. and Sambucus ebulus L. berry pomaces. The effect of fermentation time on the total fats and major lipid classes (neutral and polar) was also investigated. During the SSF, the extractable phenolics increased with 18.82% for S. ebulus L. and 11.11% for S. nigra L. The levels of antioxidant activity of methanolic extracts were also significantly enhanced. The HPLC-MS analysis indicated that the cyanidin 3-sambubioside-5-glucoside is the major phenolic compound in both fermented Sambucus fruit residues. In the early stages of fungal growth, the extracted oils (with TAGs as major lipid fraction) increased with 12% for S. nigra L. and 10.50% for S. ebulus L. The GC-MS analysis showed that the SSF resulted in a slight increase of the linoleic and oleic acids level.

  7. Omega-3 PUFA Loaded in Resveratrol-Based Solid Lipid Nanoparticles: Physicochemical Properties and Antineoplastic Activities in Human Colorectal Cancer Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Simona Serini

    2018-02-01

    Full Text Available New strategies are being investigated to ameliorate the efficacy and reduce the toxicity of the drugs currently used in colorectal cancer (CRC, one of the most common malignancies in the Western world. Data have been accumulated demonstrating that the antineoplastic therapies with either conventional or single-targeted drugs could take advantage from a combined treatment with omega-3 polyunsaturated fatty acids (omega-3 PUFA. These nutrients, shown to be safe at the dosage generally used in human trials, are able to modulate molecules involved in colon cancer cell growth and survival. They have also the potential to act against inflammation, which plays a critical role in CRC development, and to increase the anti-cancer immune response. In the present study, omega-3 PUFA were encapsulated in solid lipid nanoparticles (SLN having a lipid matrix containing resveratrol esterified to stearic acid. Our aim was to increase the efficiency of the incorporation of these fatty acids into the cells and prevent their peroxidation and degradation. The Resveratrol-based SLN were characterized and investigated for their antioxidant activity. It was observed that the encapsulation of omega-3 PUFA into the SLN enhanced significantly their incorporation in human HT-29 CRC cells in vitro, and their growth inhibitory effects in these cancer cells, mainly by reducing cell proliferation.

  8. Conversion of polar and non-polar algae oil lipids to fatty acid methyl esters with solid acid catalysts--A model compound study.

    Science.gov (United States)

    Asikainen, Martta; Munter, Tony; Linnekoski, Juha

    2015-09-01

    Bio-based fuels are becoming more and more important due to the depleting fossil resources. The production of biodiesel from algae oil is challenging compared to terrestrial vegetable oils, as algae oil consists of polar fatty acids, such as phospholipids and glycolipids, as well as non-polar triglycerides and free fatty acids common in vegetable oils. It is shown that a single sulphonated solid acid catalyst can perform the esterification and transesterification reactions of both polar and non-polar lipids. In mild reaction conditions (60-70 °C) Nafion NR50 catalyst produces methyl palmitate (FAME) from the palmitic acid derivatives of di-, and tri-glyceride, free fatty acid, and phospholipid with over 80% yields, with the glycolipid derivative giving nearly 40% yields of FAME. These results demonstrate how the polar and non-polar lipid derivatives of algal oil can be utilised as feedstocks for biodiesel production with a single catalyst in one reaction step. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Predicted radionuclide release from reactor-related unenclosed solid objects dumped in the Sea of Japan and the Pacific Ocean, east coast of Kamchatka

    International Nuclear Information System (INIS)

    Mount, M.E.; Lynn, N.M.; Warden, J.M.

    1996-06-01

    Between 1978 and 1991 reactor-related solid radioactive waste was dumped by the former Soviet Union as unenclosed objects in the Pacific Ocean, east coast of Kamchatka, and the Sea of Japan. This paper presented estimates for the current (1994) inventory of activation and corrosion products contained in the reactor-related unenclosed solid objects. In addition, simple models derived for prediction of radionuclide release from marine reactors dumped in the Kara Sea are applied to certain of the dumped objects to provide estimates of radionuclide release to the Pacific Ocean, east coast of Kamchatka, and Sea of Japan environments. For the Pacific Ocean, east coast of Kamchatka, total release rates start below 0.01 GBq yr -1 and over 1,000 years, fall to 100 Bq yr -1 . In the Sea of Japan, the total release rate starts just above 1 GBq yr - 1 , dropping off to a level less than 0.1 GBq yr -1 , extending past the year 4,000

  10. THE PROCESS OF MASS TRANSFER ON THE SOLID-LIQUID BOUNDARY LAYER DURING THE RELEASE OF DICLOFENAC SODIUM AND PAPAVERINE HYDROCHLORIDE FROM TABLETS IN A PADDLE APPARATUS.

    Science.gov (United States)

    Kasperek, Regina; Zimmer, Lukasz; Poleszak, Ewa

    2016-01-01

    The release study of diclofenac sodium (DIC) and papaverine hydrochloride (PAP) from two formulations of the tablets in the paddle apparatus using different rotation speeds to characterize the process of mass transfer on the solid-liquid boundary layer was carried out. The dissolution process of active substances was described by values of mass transfer coefficients, the diffusion boundary layer thickness and dimensionless numbers (Sh and Re). The values of calculated parameters showed that the release of DIC and PAP from tablets comprising potato starch proceeded faster than from tablets containing HPMC and microcrystalline cellulose. They were obtained by direct dependencies between Sh and Re in the range from 75 rpm to 125 rpm for both substances from all tablets. The description of the dissolution process with the dimensionless numbers make it possible to plan the drug with the required release profile under given in vitro conditions.

  11. The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles

    DEFF Research Database (Denmark)

    Liu, Jingying; Christophersen, Philip C; Yang, Mingshi

    2017-01-01

    OBJECTIVE: The present study aimed at elucidating the influence of polymorphic stability of lipid excipients on the physicochemical characters of different solid lipid microparticles (SLM), with the focus on the alteration of protein distribution in SLM. METHODS: Labeled lysozyme was incorporated...... provides updated knowledge for rational development of lipid-based formulations for oral delivery of peptide or protein drugs.......OBJECTIVE: The present study aimed at elucidating the influence of polymorphic stability of lipid excipients on the physicochemical characters of different solid lipid microparticles (SLM), with the focus on the alteration of protein distribution in SLM. METHODS: Labeled lysozyme was incorporated...... into SLM prepared with different excipients, i.e. trimyristin (TG14), glyceryl distearate (GDS), and glyceryl monostearate (GMS), by water-oil-water (w/o/w) or solid-oil-water (s/o/w) method. The distribution of lysozyme in SLM and the release of the protein from SLM were evaluated by confocal laser...

  12. Preparation and characterization of carnauba wax nanostructured lipid carriers containing benzophenone-3.

    Science.gov (United States)

    Lacerda, S P; Cerize, N N P; Ré, M I

    2011-08-01

    Nanostructured lipid carriers (NLCs) are potential active delivery systems based on mixtures of solid lipids and liquid oil. In this paper, aqueous dispersions of NLCs were prepared by a hot high-pressure homogenization technique using carnauba wax as the solid lipid and isodecyl oleate as the liquid oil. The preparation and stability parameters of benzophenone-3-loaded NLCs have been investigated concerning particle size, zeta potential and loading capacity to encapsulate benzophenone-3, a molecular sunscreen. The current investigation illustrates the effect of the composition of the lipid mixture on the entrapment efficiency, in vitro release and stability of benzophenone-3-loaded in these NLCs. A loading capacity of approximately 5% of benzophenone-3 (m(BZ-3) /m(lipids) ) was characteristic of these systems. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  13. Co-production of bio-ethanol, xylonic acid and slow-release nitrogen fertilizer from low-cost straw pulping solid residue.

    Science.gov (United States)

    Huang, Chen; Ragauskas, Arthur J; Wu, Xinxing; Huang, Yang; Zhou, Xuelian; He, Juan; Huang, Caoxing; Lai, Chenhuan; Li, Xin; Yong, Qiang

    2018-02-01

    A novel bio-refinery sequence yielding varieties of co-products was developed using straw pulping solid residue. This process utilizes neutral sulfite pretreatment which under optimal conditions (160 °C and 3% (w/v) sulfite charge) provides 64.3% delignification while retaining 90% of cellulose and 67.3% of xylan. The pretreated solids exhibited excellent enzymatic digestibility, with saccharification yields of 86.9% and 81.1% for cellulose and xylan, respectively. After pretreatment, the process of semi-simultaneous saccharification and fermentation (S-SSF) and bio-catalysis was investigated. The results revealed that decreased ethanol yields were achieved when solid loading increased from 5% to 30%. An acceptable ethanol yield of 76.8% was obtained at 20% solid loading. After fermentation, bio-catalysis of xylose remaining in fermentation broth resulted in near 100% xylonic acid (XA) yield at varied solid loadings. To complete the co-product portfolio, oxidation ammoniation of the dissolved lignin successfully transformed it into biodegradable slow-release nitrogen fertilizer with excellent agricultural properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. To evaluate the change in release from solid dispersion using sodium lauryl sulfate and model drug sulfathiazole.

    Science.gov (United States)

    Dave, Rutesh H; Patel, Hardikkumar H; Donahue, Edward; Patel, Ashwinkumar D

    2013-10-01

    The solubility of drugs remains one of the most challenging aspects of formulation development. There are numerous ways to improve the solubility of drugs amongst which the most promising strategy is solid dispersion. Different ratios of sulfathiazole: PVP-K29/32: sodium lauryl sulfate (SLS) were prepared (1:1:0.1, 1:1:0.5, 1:1:1) and various methods were employed to characterize the prepared solid dispersions, namely modulated differential scanning calorimeter, X-ray powder diffraction, Fourier Transformed Infrared Spectroscopy and dissolution studies. Lack of crystallinity was observed in internal and external systems suggesting a loss of crystallinity, whereas the physical mixtures showed a characteristic peak of sulfathiazole. In vitro dissolution results clearly showed that the incorporation of a relatively small amount of surfactants (5, 20 or 33% w/w) into a solid dispersion can improve its dissolution rates compared to binary solid dispersion (SD) alone and pure sulfathiazole. In all ratios solid dispersion internal shows a higher dissolution rate compared to a physical mixture and solid dispersion external which suggests that the way that the surfactant is incorporated into the solid dispersion plays an important role in changing the solubility of a drug. The solubilization mechanism is mainly responsible for this higher dissolution rate when we incorporate the SLS in SD.

  15. Bio-composites composed of a solid free-form fabricated polycaprolactone and alginate-releasing bone morphogenic protein and bone formation peptide for bone tissue regeneration.

    Science.gov (United States)

    Kim, MinSung; Jung, Won-Kyo; Kim, GeunHyung

    2013-11-01

    Biomedical scaffolds should be designed with highly porous three-dimensional (3D) structures that have mechanical properties similar to the replaced tissue, biocompatible properties, and biodegradability. Here, we propose a new composite composed of solid free-form fabricated polycaprolactone (PCL), bone morphogenic protein (BMP-2) or bone formation peptide (BFP-1), and alginate for bone tissue regeneration. In this study, PCL was used as a mechanical supporting component to enhance the mechanical properties of the final biocomposite and alginate was used as the deterring material to control the release of BMP-2 and BFP-1. A release test revealed that alginate can act as a good release control material. The in vitro biocompatibilities of the composites were examined using osteoblast-like cells (MG63) and the alkaline phosphatase (ALP) activity and calcium deposition were assessed. The in vitro test results revealed that PCL/BFP-1/Alginate had significantly higher ALP activity and calcium deposition than the PCL/BMP-2/Alginate composite. Based on these findings, release-controlled BFP-1 could be a good growth factor for enhancement of bone tissue growth and the simple-alginate coating method will be a useful tool for fabrication of highly functional biomaterials through release-control supplementation.

  16. In-vitro release and permeation studies of ketoconazole from optimized dermatological vehicles using powder, nanoparticles and solid dispersion forms of drug

    Science.gov (United States)

    Mohammed, Irfan A.

    To optimize the clinical efficacy of Ketoconazole from an externally applied product, this project was undertaken to evaluate the drug release/permeation profile from various dermatological vehicles using regular powder, nanoparticles and solid dispersion forms with reduced level of drug. Nanoparticles of drug were prepared by wet media milling method using Polyvinylpyrrolidone (PVP-10K) as a stabilizer. The nanoparticles were in the size range of 250-300nm. Solid dispersion was prepared by solvent evaporation method using drug to PVP-10K at a weight ratio of (1:2). Formulations containing 1% w/w drug were developed using HPMC gel, Carbomer gel and a cationic cream as the vehicles. Penetration enhancers including propylene glycol (PG), dimethylsulfoxide (DMSO) and polyethylene glycol 400 (PEG-400) at various levels were evaluated. A commercial 2% w/w ketoconazole product was included as a control for comparison. Studies were carried out with Franz Diffusion Cells using cellulose membrane and human cadaver skin for two and six hour studies. Among the formulations evaluated, the general rank order of the drug release through the cellulose membrane was observed to be: HPMC gel base > Anionic gel base > Cationic gel base > Commercial product. The addition of penetration enhancers showed variable effects in all samples evaluated. However, the HPMC gel-based vehicle showed significant effect in enhancing the drug release in the presence of DMSO. The formulation containing 1% w/w ketoconazole and 20% w/w DMSO gave a maximum drug release of 20.21% when compared to only 1.60% from the commercial product. This represents a twelve fold increase in the release of ketoconazole from the formulation. Furthermore, when the optimum gel-based formulation containing 1% w/w ketoconazole was studied over an extended period of 6 hours, it gave 36.01% drug release from the sample formulation compared to only 2.00% from the commercial product. Finally, this formulation was selected to

  17. The Effect of Millisecond Pulsed Electric Fields (msPEF) on Intracellular Drug Transport with Negatively Charged Large Nanocarriers Made of Solid Lipid Nanoparticles (SLN): In Vitro Study.

    Science.gov (United States)

    Kulbacka, Julita; Pucek, Agata; Wilk, Kazimiera Anna; Dubińska-Magiera, Magda; Rossowska, Joanna; Kulbacki, Marek; Kotulska, Małgorzata

    2016-10-01

    Drug delivery technology is still a dynamically developing field of medicine. The main direction in nanotechnology research (nanocarriers, nanovehicles, etc.) is efficient drug delivery to target cells with simultaneous drug reduction concentration. However, nanotechnology trends in reducing the carrier sizes to several nanometers limit the volume of the loaded substance and may pose a danger of uncontrolled access into the cells. On the other hand, nanoparticles larger than 200 nm in diameter have difficulties to undergo rapid diffusional transport through cell membranes. The main advantage of large nanoparticles is higher drug encapsulation efficiency and the ability to deliver a wider array of drugs. Our present study contributes a new approach with large Tween 80 solid lipid nanoparticles SLN (i.e., hydrodynamic GM-SLN-glycerol monostearate, GM, as the lipid and ATO5-SLNs-glyceryl palmitostearate, ATO5, as the lipid) with diameters DH of 379.4 nm and 547 nm, respectively. They are used as drug carriers alone and in combination with electroporation (EP) induced by millisecond pulsed electric fields. We evaluate if EP can support the transport of large nanocarriers into cells. The study was performed with two cell lines: human colon adenocarcinoma LoVo and hamster ovarian fibroblastoid CHO-K1 with coumarin 6 (C6) as a fluorescent marker for encapsulation. The biological safety of the potential treatment procedure was evaluated with cell viability after their exposure to nanoparticles and EP. The EP efficacy was evaluated by FACS method. The impact on intracellular structure organization of cytoskeleton was visualized by CLSM method with alpha-actin and beta-tubulin. The obtained results indicate low cytotoxicity of both carrier types, free and loaded with C6. The evaluation of cytoskeleton proteins indicated no intracellular structure damage. The intracellular uptake and accumulation show that SLNs do not support transport of C6 coumarin. Only application of

  18. Development of solid lipid nanoparticles containing total flavonoid extract from Dracocephalum moldavica L. and their therapeutic effect against myocardial ischemia–reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Tan ME

    2017-04-01

    Full Text Available Mei-e Tan,1–3,* Cheng-hui He,3,* Wen Jiang,4 Cheng Zeng,2–4 Ning Yu,3 Wei Huang,2 Zhong-gao Gao,2 Jian-guo Xing3 1Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, 2State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 3Xinjiang Key Laboratory of Uighur Medicines, Xinjiang Institute of Materia Medica, 4Xinjiang Medical University, Urumqi, People’s Republic of China *These authors contributed equally to this work Abstract: Total flavonoid extract from Dracocephalum moldavica L. (TFDM contains effective components of D. moldavica L. that have myocardial protective function. However, the cardioprotection function of TFDM is undesirable due to its poor solubility. In order to improve the solubility and efficacy of TFDM, we developed TFDM-loaded solid lipid nanoparticles (TFDM-SLNs and optimized the formulation of TFDM-SLNs using central composite design and response surface methodology. The physicochemical properties of TFDM-SLNs were characterized, and the pharmacodynamics was investigated using the myocardial ischemia–reperfusion injury model in rats. The nanoparticles of optimal formulation for TFDM-SLNs were spherical in shape with the average particle size of 104.83 nm and had a uniform size distribution with the polydispersity index value of 0.201. TFDM-SLNs also had a negative zeta potential of -28.7 mV to ensure the stability of the TFDM-SLNs emulsion system. The results of pharmacodynamics demonstrated that both TFDM and TFDM-SLN groups afforded myocardial protection, and the protective effect of TFDM-SLNs was significantly superior to that of TFDM alone, based on the infarct area, histopathological examination, cardiac enzyme levels and inflammatory factors in serum. Due to the optimal

  19. Sorption-desorption processes of radioisotopes with solid materials from liquid releases and atmosphere deposits. The distribution coefficient (Ksub(d)), its uses, limitations, and practical applications

    International Nuclear Information System (INIS)

    Saas, Arsene

    1979-03-01

    The various sorption-desorption processes of radionuclides with environmental materials are presented. The parameters governing the distribution coefficient are reviewed in the light of various examples. The factors affecting equilibria between the different phases are: reaction time, concentration of the solid phase, water quality, salinity, competition between ions, concentration of radioisotopes or stable isotopes, pH of the mobile phase, particle diameter, chemical form of the radioisotopes, nature of the solid phase, temperature. The effects of the biological parameters on the distribution coefficient are discussed. Biological processes affect the main chemical transformations: mineralization, insolubilization, oxidation-reduction, complexation, ... The importance of these processes is demonstrated by a number of examples in various media. Finally, the practical use of Ksub(d) in the assessment of the environmental impact of radioactive releases is developed, with special emphasis on the limits of its use in siting studies and its essential interest in specifying pathways and capacity of a river system [fr

  20. Idaho National Engineering Laboratory response to the December 13, 1991, Congressional inquiry on offsite release of hazardous and solid waste containing radioactive materials from Department of Energy facilities

    International Nuclear Information System (INIS)

    Shapiro, C.; Garcia, K.M.; McMurtrey, C.D.; Williams, K.L.; Jordan, P.J.

    1992-05-01

    This report is a response to the December 13, 1991, Congressional inquiry that requested information on all hazardous and solid waste containing radioactive materials sent from Department of Energy facilities to offsite facilities for treatment or disposal since January 1, 1981. This response is for the Idaho National Engineering Laboratory. Other Department of Energy laboratories are preparing responses for their respective operations. The request includes ten questions, which the report divides into three parts, each responding to a related group of questions. Part 1 answers Questions 5, 6, and 7, which call for a description of Department of Energy and contractor documentation governing the release of waste containing radioactive materials to offsite facilities. ''Offsite'' is defined as non-Department of Energy and non-Department of Defense facilities, such as commercial facilities. Also requested is a description of the review process for relevant release criteria and a list of afl Department of Energy and contractor documents concerning release criteria as of January 1, 1981. Part 2 answers Questions 4, 8, and 9, which call for information about actual releases of waste containing radioactive materials to offsite facilities from 1981 to the present, including radiation levels and pertinent documentation. Part 3 answers Question 10, which requests a description of the process for selecting offsite facilities for treatment or disposal of waste from Department of Energy facilities. In accordance with instructions from the Department of Energy, the report does not address Questions 1, 2, and 3

  1. Development of solid lipid nanoparticles containing total flavonoid extract from Dracocephalum moldavica L. and their therapeutic effect against myocardial ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Tan, Mei-E; He, Cheng-Hui; Jiang, Wen; Zeng, Cheng; Yu, Ning; Huang, Wei; Gao, Zhong-Gao; Xing, Jian-Guo

    2017-01-01

    Total flavonoid extract from Dracocephalum moldavica L. (TFDM) contains effective components of D. moldavica L. that have myocardial protective function. However, the cardioprotection function of TFDM is undesirable due to its poor solubility. In order to improve the solubility and efficacy of TFDM, we developed TFDM-loaded solid lipid nanoparticles (TFDM-SLNs) and optimized the formulation of TFDM-SLNs using central composite design and response surface methodology. The physicochemical properties of TFDM-SLNs were characterized, and the pharmacodynamics was investigated using the myocardial ischemia-reperfusion injury model in rats. The nanoparticles of optimal formulation for TFDM-SLNs were spherical in shape with the average particle size of 104.83 nm and had a uniform size distribution with the polydispersity index value of 0.201. TFDM-SLNs also had a negative zeta potential of -28.7 mV to ensure the stability of the TFDM-SLNs emulsion system. The results of pharmacodynamics demonstrated that both TFDM and TFDM-SLN groups afforded myocardial protection, and the protective effect of TFDM-SLNs was significantly superior to that of TFDM alone, based on the infarct area, histopathological examination, cardiac enzyme levels and inflammatory factors in serum. Due to the optimal quality and the better myocardial protective effect, TFDM-SLNs are expected to become a safe and effective nanocarrier for the oral delivery of TFDM.

  2. Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography.

    Science.gov (United States)

    Sun, Jihong; Zhang, Shizheng; Jiang, Shaojie; Bai, Weixian; Liu, Fei; Yuan, Hong; Ji, Jiansong; Luo, Jingfeng; Han, Guocan; Chen, Lumin; Jin, Yin; Hu, Peng; Yu, Lei; Yang, Xiaoming

    2016-09-01

    Magnetic resonance (MR) contrast agents focusing on special functions are required to improve cancer diagnosis, particularly in the early stages. Here, we designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a tumor-absorbable nanoparticle contrast agent for the histological confirmation of MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo via direct uptake of this contrast agent, which displayed reasonable T1 relaxivity and no significant cytotoxicity at the experimental concentrations in human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In vitro cell uptake experiments demonstrated that contrast agent absorption by the two types of cancer cells was concentration-dependent in the safe concentration range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more significant enhancement at the tumor site compared with the infusion of Gd-DTPA in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots distributed from the tumor capsule into the tumor. This study establishes the "proof-of-principle" of a new MRI technique wherein colorectal tumors are enhanced via direct absorption or uptake of the nanoparticle contrast agent.

  3. Comparative Neuroprotective Effects of Dietary Curcumin and Solid Lipid Curcumin Particles in Cultured Mouse Neuroblastoma Cells after Exposure to Aβ42

    Directory of Open Access Journals (Sweden)

    Panchanan Maiti

    2017-01-01

    Full Text Available Aggregation of amyloid beta protein (Aβ and phosphorylated tau (p-Tau plays critical roles in pathogenesis of Alzheimer’s disease (AD. As an antiamyloid natural polyphenol, curcumin (Cur has a potential role in prevention of neurodegeneration in AD. However, due to limited absorption of the dietary Cur, the solid lipid Cur particles (SLCP have been suggested as being more effective for AD therapy. In the present study, we compared the role of dietary Cur and SLCP on oxidative stress, neuronal death, p-Tau level, and certain cell survival markers in vitro, after exposure to Aβ42. Mouse neuroblastoma cells were exposed to Aβ42 for 24 h and incubated with or without dietary Cur and/or SLCP. Reactive oxygen species (ROS, apoptotic cell death, p-Tau, and tau kinase (including GSK-3β and cell survival markers, such as total Akt, phosphorylated Akt, and PSD95 levels were investigated. SLCP showed greater permeability than dietary Cur in vitro, decreased ROS production, and prevented apoptotic death. In addition, SLCP also inhibited p-Tau formation and significantly decreased GSK-3β levels. Further, the cell survival markers, such as total Akt, p-Akt, and PSD95 levels, were more effectively maintained by SLCP than dietary Cur in Aβ42 exposed cells. Therefore, SLCP may provide greater neuroprotection than dietary Cur in Alzheimer’s disease.

  4. In vitro antitumor efficacy of berberine: solid lipid nanoparticles against human HepG2, Huh7 and EC9706 cancer cell lines

    Science.gov (United States)

    Meng, Xiang-Ping; Wang, Xiao; Wang, Huai-ling; Chen, Tong-sheng; Wang, Yi-fei; Wang, Zhi-ping

    2016-03-01

    Hepatocarcinoma and esophageal squamous cell carcinomas threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma and esophageal carcinoma to chemotherapy. Berberine (Ber), an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-hepatocarcinoma and antiesophageal carcinoma effects. However its low oral bioavailability restricts its wide application. In this report, Ber loaded solid lipid nanoparticles (Ber-SLN) was prepared by hot melting and then high pressure homogenization technique. The in vitro anti-hepatocarcinoma and antiesophageal carcinoma effects of Ber-SLN relative to efficacy of bulk Ber were evaluated. The particle size and zeta potential of Ber-SLN were 154.3 ± 4.1 nm and -11.7 ± 1.8 mV, respectively. MTT assay showed that Ber-SLN effectively inhibited the proliferation of human HepG2 and Huh7 and EC9706 cells, and the corresponding IC50 value was 10.6 μg/ml, 5.1 μg/ml, and 7.3 μg/ml (18.3μg/ml, 6.5μg/ml, and 12.4μg/ml μg/ml of bulk Ber solution), respectively. These results suggest that the delivery of Ber-SLN is a promising approach for treating tumors.

  5. Design of sustained-release nitrendipine microspheres having solid dispersion structure by quasi-emulsion solvent diffusion method

    DEFF Research Database (Denmark)

    Cui, Fude; Yang, Mingshi; Jiang, Yanyan

    2003-01-01

    crystallization technique, i.e. quasi-emulsion solvent diffusion method. The factors of effect on micromeritic properties and release profiles of the resultant microspheres were investigated. And the bioavailability of nitrendipine microspheres was evaluated in six healthy dogs. The results showed...... that the particle size of microspheres was determined mainly by the agitation speed. The dissolution rate of nitrendipine from microspheres was enhanced significantly with increasing the amount of dispersing agents, and sustained by adding retarding agents. The release rate of microspheres could be controlled...

  6. In Situ Lipolysis and Synchrotron Small-Angle X-ray Scattering for the Direct Determination of the Precipitation and Solid-State Form of a Poorly Water-Soluble Drug During Digestion of a Lipid-Based Formulation

    DEFF Research Database (Denmark)

    Khan, Jamal; Hawley, Adrian; Rades, Thomas

    2016-01-01

    In situ lipolysis and synchrotron small-angle X-ray scattering (SAXS) were used to directly detect and elucidate the solid-state form of precipitated fenofibrate from the digestion of a model lipid-based formulation (LBF). This method was developed in light of recent findings that indicate variab...... on drugs, and experimental conditions, which are anticipated to produce altered solid-state forms upon the precipitation of drug (i.e., polymorphs, amorphous forms, and salts). © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci....

  7. In vitro dissolution study of acetylsalicylic acid solid dispersions. Tunable drug release allowed by the choice of polymer matrix

    Czech Academy of Sciences Publication Activity Database

    Policianová, Olivia; Brus, Jiří; Hrubý, Martin; Urbanová, Martina

    2015-01-01

    Roč. 20, č. 8 (2015), s. 935-940 ISSN 1083-7450 R&D Projects: GA ČR(CZ) GA14-03636S; GA ČR GPP106/11/P426 Grant - others:AV ČR(CZ) M200501201 Program:M Institutional support: RVO:61389013 Keywords : acetylsallicylic acid * controlled drug release * polymers Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.566, year: 2015

  8. Chemical form of tritium released from solid breeder materials and the influences of it on a bred tritium recovery systems

    International Nuclear Information System (INIS)

    Furukubo, Y.; Nishikawa, M.; Nishida, Y.; Kinjyo, T.; Tanifuji, Takaaki; Kawamura, Yoshinori; Enoeda, Mikio

    2004-01-01

    The ratio of HTO in total tritium was measured at release of the bred tritium to the purge gas with hydrogen using the thermal release after irradiation method, where neutron irradiation was performed at JRR-3 reactor in JAERI or KUR reactor in Kyoto University. It is experimentally confirmed in this study that not a small portion of bred tritium is released to the purge gas in the form of HTO form ceramic breeder materials even when hydrogen is added to the purge gas. The chemical composition is to be decided by the competitive reaction at the grain surface of a ceramic breeder material where desorption reaction, isotope exchange reaction 1, isotope exchange reaction 2 and water formation reaction are considered to take part. Observation in this study implies that it is necessary to have a bred tritium recovery system applicable for both HT and HTO form to recover whole bred tritium. The chemical composition also decides the amount of tritium transferable to the cooling water of the electricity generation system through the structural material in the blanket system. Permeation behavior of tritium through some structural materials at various conditions are also discussed. (author)

  9. Sampling and analytical procedures for the determination of VOCs released into air from natural and anthropogenic sources: A comparison between SPME (Solid Phase Micro Extraction) and ST (Solid Trap) methods

    International Nuclear Information System (INIS)

    Tassi, F.; Capecchiacci, F.; Buccianti, A.; Vaselli, O.

    2012-01-01

    In the present study, two sampling and analytical methods for VOC determination in fumarolic exhalations related to hydrothermal-magmatic reservoirs in volcanic and geothermal areas and biogas released from waste landfills were compared: (a) Solid Traps (STs), consisting of three phase (Carboxen B, Carboxen C and Carbosieve S111) absorbent stainless steel tubes and (b) Solid Phase Micro Extraction (SPME) fibers, composed of DiVinylBenzene (DVB), Carboxen and PolyDimethylSiloxane. These techniques were applied to pre-concentrate VOCs discharged from: (i) low-to-high temperature fumaroles collected at Vulcano Island, Phlegrean Fields (Italy), and Nisyros Island (Greece), (ii) recovery wells in a solid waste disposal site located near Florence (Italy). A glass condensing system cooled with water was used to collect the dry fraction of the fumarolic gases, in order to allow more efficient VOC absorption avoiding any interference by water vapor and acidic gases, such as SO 2 , H 2 S, HF and HCl, typically present at relatively high concentrations in these fluids. Up to 37 organic species, in the range of 40–400 m/z, were determined by coupling gas chromatography to mass spectrometry (GC–MS). This study shows that the VOC compositions of fumaroles and biogas determined via SPME and ST are largely consistent and can be applied to the analysis of VOCs in gases released from different natural and anthropogenic environments. The SPME method is rapid and simple and more appropriate for volcanic and geothermal emissions, where VOCs are present at relatively high concentrations and prolonged gas sampling may be hazardous for the operator. The ST method, allowing the collection of large quantities of sample, is to be preferred to analyze the VOC composition of fluids from diffuse emissions and air, where these compounds are present at relatively low concentrations.

  10. Energy Trapping, Release, and Transport in Three-Dimensional Energetic Solids and Molecular Crystals: Theory of Defects and Impurities.

    Science.gov (United States)

    1984-12-31

    and 3. T. Waber, Concerning the Trapping of Positrons in Ionic Solids, in Positron Annihilation , P. G. Coleman, S. C. Sharma and L. M. Diana, Eds., 682...1982). *144. A. B. Kunz and 3. T. Waber, A Theoretical Study of the Binding of Positrons to Gaseous Molecules, in Positron Annihilation . P. G. Coleman, S...variety of other cases which include systems in unusual charge states such as Fe + in SrTiOz or Fe in MgO . Impurity systems in their excited states are

  11. Docetaxel-loaded solid lipid nanoparticles as a basis for a targeted and dose-sparing personalized breast cancer treatment strategy

    Directory of Open Access Journals (Sweden)

    Danilova NV

    2015-03-01

    Full Text Available Natalia V Danilova,1,2 Zhomart R Kalzhanov,3 Nina A Nefedova,2 Pavel G Mal’kov,2 Ioannis P Kosmas,1,4 Marina Y Eliseeva,1,5 Ospan A Mynbaev1,5,6 1International Translational Medicine and Biomodeling Research Team, MIPT Center for Human Physiology, Laboratory of Cellular and Molecular Technologies, Moscow Institute of Physics and Technology, State University, 2Department of Physiology and Basic Pathology, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russia; 3Department of Human Metabolism, Academic Unit of Reproductive and Developmental Medicine, Sheffield University, Sheffield, UK; 4Department of Obstetrics and Gynecology, Ioannina State General Hospital G Chatzikosta, Ioannina, Greece; 5Department of Obstetrics, Gynecology and Reproductive Medicine, Peoples’ Friendship University of Russia, 6Laboratory of Immunology, Moscow State University of Medicine and Dentistry named after AI Evdokimov, Moscow, Russia The long-term survival rate of patients with breast cancer was improved by the application of systemic adjuvant chemotherapy,1 although the primary breast cancer treatment strategy consists of mastectomy with lymphadenectomy and radiotherapy followed by breast reconstruction.2–5 Unfortunately, most adjuvant chemotherapeutic agents trigger major side effects.1,6 Therefore, we have read with great interest an article in the International Journal of Nanomedicine on the design of docetaxel-loaded solid lipid nanoparticles (DSNs aimed at reducing the systemic toxicity of standardized docetaxel treatment.7 Read the original article 

  12. Physicochemical characterization and in vivo bioluminescence imaging of nanostructured lipid carriers for targeting the brain: apomorphine as a model drug

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Shu-Hui [Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan (China); Wen, Chih-Jen; Yen, Tzu-Chen [Animal Molecular Imaging Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan 333, Taiwan (China); Al-Suwayeh, S A; Fang, Jia-You [Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh (Saudi Arabia); Chang, Hui-Wen, E-mail: fajy@mail.cgu.edu.tw [Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan 333, Taiwan (China)

    2010-10-08

    Nanostructured lipid carriers (NLCs) were prepared to investigate whether the duration of brain targeting and accumulation of drugs in the brain can be improved by intravenous delivery. NLCs were developed using cetyl palmitate as the lipid matrix, squalene as the cationic surfactant, and Pluronic F68, polysorbate 80 and polyethylene glycol as the interfacial additives. Solid lipid nanoparticles (SLNs) and lipid emulsions (LEs) were also prepared for comparison. An anti-Parkinson's drug, apomorphine, was used as the model drug. Nuclear magnetic resonance and differential scanning calorimetry showed possible interactions between the solid and liquid lipids in the inner core. The lipid nanoparticles with different compositions were characterized by mean size, zeta potential, apomorphine encapsulation and in vitro drug release. NLCs were 370-430 nm in size, which was between the sizes of the SLNs and LEs. A cationic surfactant was used to produce a positive surface charge of 42-50 mV. The base form of apomorphine was successfully entrapped by NLCs with an entrapment percentage of > 60%. The loading of apomorphine in nanoparticles resulted in a slower release behavior compared to the aqueous solution, with LEs showing the lowest release. In vivo real-time bioluminescence imaging of the rat brain revealed that NLCs could be targeted, through certain vessels, to selected brain regions. This effect was further confirmed by imaging the entire brain and brain slices. The results indicated that NLCs with moderate additives are a promising controlled-release and drug-targeting system.

  13. Physicochemical characterization and in vivo bioluminescence imaging of nanostructured lipid carriers for targeting the brain: apomorphine as a model drug

    International Nuclear Information System (INIS)

    Hsu, Shu-Hui; Wen, Chih-Jen; Yen, Tzu-Chen; Al-Suwayeh, S A; Fang, Jia-You; Chang, Hui-Wen

    2010-01-01

    Nanostructured lipid carriers (NLCs) were prepared to investigate whether the duration of brain targeting and accumulation of drugs in the brain can be improved by intravenous delivery. NLCs were developed using cetyl palmitate as the lipid matrix, squalene as the cationic surfactant, and Pluronic F68, polysorbate 80 and polyethylene glycol as the interfacial additives. Solid lipid nanoparticles (SLNs) and lipid emulsions (LEs) were also prepared for comparison. An anti-Parkinson's drug, apomorphine, was used as the model drug. Nuclear magnetic resonance and differential scanning calorimetry showed possible interactions between the solid and liquid lipids in the inner core. The lipid nanoparticles with different compositions were characterized by mean size, zeta potential, apomorphine encapsulation and in vitro drug release. NLCs were 370-430 nm in size, which was between the sizes of the SLNs and LEs. A cationic surfactant was used to produce a positive surface charge of 42-50 mV. The base form of apomorphine was successfully entrapped by NLCs with an entrapment percentage of > 60%. The loading of apomorphine in nanoparticles resulted in a slower release behavior compared to the aqueous solution, with LEs showing the lowest release. In vivo real-time bioluminescence imaging of the rat brain revealed that NLCs could be targeted, through certain vessels, to selected brain regions. This effect was further confirmed by imaging the entire brain and brain slices. The results indicated that NLCs with moderate additives are a promising controlled-release and drug-targeting system.

  14. Can lipid nanoparticles improve intestinal absorption?

    Science.gov (United States)

    Mendes, M; Soares, H T; Arnaut, L G; Sousa, J J; Pais, A A C C; Vitorino, C

    2016-12-30

    Lipid nanoparticles and their multiple designs have been considered appealing nanocarrier systems. Bringing the benefits of these nanosystems together with conventional coating technology clearly results in product differentiation. This work aimed at developing an innovative solid dosage form for oral administration based on tableting nanostructured lipid carriers (NLC), coated with conventional polymer agents. NLC dispersions co-encapsulating olanzapine and simvastatin (Combo-NLC) were produced by high pressure homogenization, and evaluated in terms of scalability, drying procedure, tableting and performance from in vitro release, cytotoxicity and intestinal permeability stand points. Factorial design indicated that the scaling-up of the NLC production is clearly feasible. Spray-drying was the method selected to obtain dry particles, not only because it consists of a single step procedure, but also because it facilitates the coating process of NLC with different polymers. Modified NLC formulations with the polymers allowed obtaining distinct release mechanisms, comprising immediate, delayed and prolonged release. Sureteric:Combo-NLC provided a low cytotoxicity profile, along with a ca. 12-fold OL/3-fold SV higher intestinal permeability, compared to those obtained with commercial tablets. Such findings can be ascribed to drug protection and control over release promoted by NLC, supporting them as a versatile platform able to be modified according to the intended needs. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Lipid Structure in Triolein Lipid Droplets

    DEFF Research Database (Denmark)

    Chaban, Vitaly V; Khandelia, Himanshu

    2014-01-01

    of a mass of hydrophobic lipid esters coved by phospholipid monolayer. The small size and unique architecture of LDs makes it complicated to study LD structure by modern experimental methods. We discuss coarse-grained molecular dynamics (MD) simulations of LD formation in systems containing 1-palmitoyl-2...... to coarse-grained simulations, the presence of PE lipids at the interface has a little impact on distribution of components and on the overall LD structure. (4) The thickness of the lipid monolayer at the surface of the droplet is similar to the thickness of one leaflet of a bilayer. Computer simulations......Lipid droplets (LDs) are primary repositories of esterified fatty acids and sterols in animal cells. These organelles originate on the lumenal or cytoplasmic side of endoplasmic reticulum (ER) membrane and are released to the cytosol. In contrast to other intracellular organelles, LDs are composed...

  16. Factors affecting the release of radioactivity to the biosphere during deep geologic disposal of radioactive solids through underground water

    International Nuclear Information System (INIS)

    Solomah, A.G.

    1984-01-01

    The chemical alteration formed by ground water on the solidified radioactive waste during deep geologic disposal represents the most likely mechanism by which dangerous radioactive species could be reintroduced into the biosphere. Knowing the geologic history of the repository, the chemistry of the ground water and the mechanisms involved in the corrosion of the radioactive solids can provide help to predict the long-term stability of these materials. The factors that must be considered in order to assess the safety and the risk associated with such a disposal strategy are presented. The leaching behavior of a solidified radioactive waste form called SYNROC-B (SYNthetic ROCks) is discussed. Different simulated ground water brines similar to those of the repository sites were prepared and used as the leaching media in leaching experiments

  17. WARP3D-Release 10.8: Dynamic Nonlinear Analysis of Solids using a Preconditioned Conjugate Gradient Software Architecture

    Science.gov (United States)

    Koppenhoefer, Kyle C.; Gullerud, Arne S.; Ruggieri, Claudio; Dodds, Robert H., Jr.; Healy, Brian E.

    1998-01-01

    This report describes theoretical background material and commands necessary to use the WARP3D finite element code. WARP3D is under continuing development as a research code for the solution of very large-scale, 3-D solid models subjected to static and dynamic loads. Specific features in the code oriented toward the investigation of ductile fracture in metals include a robust finite strain formulation, a general J-integral computation facility (with inertia, face loading), an element extinction facility to model crack growth, nonlinear material models including viscoplastic effects, and the Gurson-Tver-gaard dilatant plasticity model for void growth. The nonlinear, dynamic equilibrium equations are solved using an incremental-iterative, implicit formulation with full Newton iterations to eliminate residual nodal forces. The history integration of the nonlinear equations of motion is accomplished with Newmarks Beta method. A central feature of WARP3D involves the use of a linear-preconditioned conjugate gradient (LPCG) solver implemented in an element-by-element format to replace a conventional direct linear equation solver. This software architecture dramatically reduces both the memory requirements and CPU time for very large, nonlinear solid models since formation of the assembled (dynamic) stiffness matrix is avoided. Analyses thus exhibit the numerical stability for large time (load) steps provided by the implicit formulation coupled with the low memory requirements characteristic of an explicit code. In addition to the much lower memory requirements of the LPCG solver, the CPU time required for solution of the linear equations during each Newton iteration is generally one-half or less of the CPU time required for a traditional direct solver. All other computational aspects of the code (element stiffnesses, element strains, stress updating, element internal forces) are implemented in the element-by- element, blocked architecture. This greatly improves

  18. CAR T Cells Releasing IL-18 Convert to T-Bethigh FoxO1low Effectors that Exhibit Augmented Activity against Advanced Solid Tumors

    Directory of Open Access Journals (Sweden)

    Markus Chmielewski

    2017-12-01

    Full Text Available Adoptive therapy with chimeric antigen receptor (CAR-redirected T cells has achieved remarkable efficacy in the treatment of hematopoietic malignancies. However, eradicating large solid tumors in advanced stages of the disease remains challenging. We explored augmentation of the anti-tumor immune reaction by establishing an acute inflammatory reaction. Systematic screening indicates that IL-18 polarizes CAR T cells toward T-bethigh FoxO1low effectors with an acute inflammatory response. CAR T cells engineered with inducible IL-18 release exhibited superior activity against large pancreatic and lung tumors that were refractory to CAR T cells without cytokines. IL-18 CAR T cell treatment was accompanied by an overall change in the immune cell landscape associated with the tumor. More specifically, CD206− M1 macrophages and NKG2D+ NK cells increased in number, whereas Tregs, suppressive CD103+ DCs, and M2 macrophages decreased, suggesting that “iIL18 TRUCKs” can be used to sensitize large solid tumor lesions for successful immune destruction.

  19. Irradiaiton facilities for testing solid and liquid blanket breeder materials with in-situ tritium release measurements in the HFR Petten

    International Nuclear Information System (INIS)

    Conrad, R.; Debarberis, L.

    1991-01-01

    Lithium-based tritium breeder materials for solid and liquid fusion reactor blanket concepts are being tested in the High Flux Reactor (HFR) Petten with in-situ tritium release measurements since 1985, within the European Fusion Technology Programme and the BEATRIX-I programme. Ceramic breeder materials are being tested in the EXOTIC and COMPLIMENT experimental programmes and the liquid breeder material, Pb-17Li, is being tested in the LIBRETTO experimental programme. The in-pile experiments are performed with irradiation facilities developed by the Joint Research Centre (JRC) Petten. The irradiation vehicles are multi-channel rigs. The sample holders consist of independent, fully instrumented and triple contained capsules. The out-of-pile experimental equipment consist of twelve independent circuits for on-line tritium release and tritium permeation measurements and eight independent circuits for temperature control. The experimental achievements obtained so far contribute to the selection of candidate tritium breeder materials for blanket concepts of near future machines like NET, ITER and DEMO. (orig.)

  20. Solid State NMR Characterization of Ibuprofen:Nicotinamide Cocrystals and New Idea for Controlling Release of Drugs Embedded into Mesoporous Silica Particles.

    Science.gov (United States)

    Skorupska, Ewa; Kaźmierski, Sławomir; Potrzebowski, Marek J

    2017-05-01

    Grinding and melting methods were employed for synthesis of pharmaceutical cocrystals formed by racemic (R/S) and entiomeric (S) ibuprofen (IBU) and nicotinamide (NA) as coformer. Obtained (R/S)-IBU:NA and (S)-IBU:NA cocrystals were fully characterized by means of advanced one- and two-dimensional solid state nuclear magnetic resonance (SS NMR) techniques with very fast magic angle spinning (MAS) at 60 kHz. The distinction in molecular packing and specific hydrogen bonding pattern was clearly recognized by analysis of 1 H, 13 C, and 15 N spectra. It is concluded from these studies that both methods (grinding and melting) provide exactly the same, specific forms of cocrystals. Thermal solvent-free (TSF) approach was used for loading of (R/S)-IBU:NA and (S)-IBU:NA into the pores of MCM-41 mesoporous silica particle (MSP). The progress and efficiency of this process was analyzed by NMR spectroscopy. It has been confirmed that TSF method is an effective and safe technique of filling the MSP pores with active pharmaceutical ingredients (APIs). By analyzing the NMR results, it has been further proved that excess of IBU and NA components, which are not embedded into the pores during melting and cooling, crystallize on the MCM-41 walls preserving very specific arrangement, characteristic for crystalline samples. By investigating kinetic of release for (R/S)-IBU/MCM-41, (S)-IBU:NA/MCM-41, and (R/S)-IBU:NA/MCM-41 samples containing active components exclusively inside of the pores, it was revealed that release of IBU is much faster for the first of the samples compared to those containing IBU and NA inside the pores. The hypothesis that the rate of release of API can be controlled by specific composition of cocrystal embedded into the MSP pore was further supported by study of (R/S)-IBU:BA/MCM-41 sample with benzoic acid (BA) as coformer.

  1. Optimization of LDL targeted nanostructured lipid carriers of 5-FU by a full factorial design

    Directory of Open Access Journals (Sweden)

    Sare Andalib

    2012-01-01

    Full Text Available Background: Nanostructured lipid carriers (NLC are a mixture of solid and liquid lipids or oils as colloidal carrier systems that lead to an imperfect matrix structure with high ability for loading water soluble drugs. The aim of this study was to find the best proportion of liquid and solid lipids of different types for optimization of the production of LDL targeted NLCs used in carrying 5-Fu by the emulsification-solvent evaporation method. Materials and Methods: The influence of the lipid type, cholesterol or cholesteryl stearate for targeting LDL receptors, oil type (oleic acid or octanol, lipid and oil% on particle size, surface charge, drug loading efficiency, and drug released percent from the NLCs were studied by a full factorial design. Results: The NLCs prepared by 54.5% cholesterol and 25% of oleic acid, showed optimum results with particle size of 105.8 nm, relatively high zeta potential of −25 mV, drug loading efficiency of 38% and release efficiency of about 40%. Scanning electron microscopy of nanoparticles confirmed the results of dynamic light scattering method used in measuring the particle size of NLCs. Conclusions: The optimization method by a full factorial statistical design is a useful optimization method for production of nanostructured lipid carriers.

  2. Optimization of LDL targeted nanostructured lipid carriers of 5-FU by a full factorial design.

    Science.gov (United States)

    Andalib, Sare; Varshosaz, Jaleh; Hassanzadeh, Farshid; Sadeghi, Hojjat

    2012-01-01

    Nanostructured lipid carriers (NLC) are a mixture of solid and liquid lipids or oils as colloidal carrier systems that lead to an imperfect matrix structure with high ability for loading water soluble drugs. The aim of this study was to find the best proportion of liquid and solid lipids of different types for optimization of the production of LDL targeted NLCs used in carrying 5-Fu by the emulsification-solvent evaporation method. The influence of the lipid type, cholesterol or cholesteryl stearate for targeting LDL receptors, oil type (oleic acid or octanol), lipid and oil% on particle size, surface charge, drug loading efficiency, and drug released percent from the NLCs were studied by a full factorial design. The NLCs prepared by 54.5% cholesterol and 25% of oleic acid, showed optimum results with particle size of 105.8 nm, relatively high zeta potential of -25 mV, drug loading efficiency of 38% and release efficiency of about 40%. Scanning electron microscopy of nanoparticles confirmed the results of dynamic light scattering method used in measuring the particle size of NLCs. The optimization method by a full factorial statistical design is a useful optimization method for production of nanostructured lipid carriers.

  3. Nanostructured lipid carrier system for topical delivery of terbinafine hydrochloride

    Directory of Open Access Journals (Sweden)

    Bharti Gaba

    2015-12-01

    Full Text Available The main aim of the present study was to develop and evaluate Terbinafine HCl (TH-loaded nanostructured lipid carrier (NLC for the treatment of fungal infection via topical administration. Fungal infections are tremendously widespread and the treatments are effective but associated toxicities restrict their use. TH-NLC was prepared using high pressure homogenization technique using Glyceryl Monostearate (GMS as solid lipid, Labrasol as liquid lipid and Pluronic F-127 as surfactant, binary lipid phase was selected in the ratio 6:4 w/w (solid:liquid lipid ratio. The mean diameter of optimized TH-NLCs was found to be 128 ± 4.5 nm. Spherical shape and size were confirmed using scanning electron microscopy (SEM and transmission electron microscopy (TEM analyses. The in vitro release studies showed 92.60 ± 0.87% drug release over 24 h as compared to the marketed formulation which showed only 82.826 ± 0.29%. Ex vivo skin permeation study showed about 86.35% permeation however from the marketed formulation it showed 69.41%. The pharmacodynamic studies indicated that TH-NLC (771 ± 41.797 CFUs gel efficiently reduced the fungal burden in shorter duration of time as compared to marketed formulation (1558 ± 140.524 CFUs and dispersion (95,582 ± 2316.619 CFUs (p value > 0.001. Therefore, it can be concluded that the developed NLCs showed a sustained release pattern and reduction of fungal burden in the infected area. Hence, TH-NLC could be a potential alternative for treatment of topical fungal infection after clinical evaluation in near future.

  4. From solid to liquid: assessing the release of organic matter into soil solution in response to land-use conversion in Brazilian Oxisols

    Science.gov (United States)

    James, Jason; Gross, Cole; Dwivedi, Pranjal; Bernardi, Rodolpho; Guerrini, Irae; Harrison, Rob; Butman, David

    2017-04-01

    horizons may be less likely to be intercepted, and thus preferentially leached to groundwater. Native Cerrado forests had substantially more roots compared to Eucalyptus, and also released substantially larger quantities of DOM from their O horizons. Processes operating at the interface between solid and liquid, terrestrial and aquatic are a key unknown in the global carbon cycle. This research permits a unique snapshot into the relationship between DOM and SOM and the response of these pools to land-use change in Brazil.

  5. LC-MS/MS analysis of lipidized analogs of prolactin-releasing peptide utilizing a monolithic column and simple sample preparation

    Czech Academy of Sciences Publication Activity Database

    Zemenová, Jana; Sýkora, D.; Freislebenová, A.; Maletínská, Lenka

    2017-01-01

    Roč. 9, č. 17 (2017), s. 1319-1328 ISSN 1757-6180 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : LC-MS * lipopeptides * monolithic column * prolactin-releasing peptide * stability Subject RIV: CE - Biochemistry OBOR OECD: Biochemical research methods Impact factor: 2.673, year: 2016

  6. Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration

    Czech Academy of Sciences Publication Activity Database

    Maletínská, L.; Nagelová, V.; Tichá, A.; Zemenová, J.; Pirník, Z.; Holubová, M.; Špolcová, A.; Mikulášková, Barbora; Blechová, M.; Sýkora, D.; Lacinová, Z.; Haluzík, M.; Železná, B.; Kuneš, Jaroslav

    2015-01-01

    Roč. 39, č. 6 (2015), s. 986-993 ISSN 0307-0565 R&D Projects: GA TA ČR(CZ) TE01020028 Institutional support: RVO:67985823 Keywords : food intake * prolactin-releasing peptide * GPR10 receptor Subject RIV: CE - Biochemistry Impact factor: 5.337, year: 2015

  7. Nanostructured Lipid Carriers Loaded with Baicalin: An Efficient Carrier for Enhanced Antidiabetic Effects.

    Science.gov (United States)

    Shi, Feng; Wei, Zheng; Zhao, Yingying; Xu, Ximing

    2016-01-01

    Recent studies have demonstrated that baicalin has antihyperglycemic effects by inhibiting lipid peroxidation. Baicalin is low hydrophilic and poorly absorbed after oral administration. Thus, a suitable formulation is highly desired to overcome the disadvantages of baicalin. The objective of this work was to prepare baicalin-loaded nanostructured lipid carriers (B-NLCs) for enhanced antidiabetic effects. B-NLCs were prepared by high-pressure homogenization method using Precirol as the solid lipid and Miglyol as the liquid lipid. The properties of the NLCs, such as particle size, zeta potential (ZP), and drug encapsulation efficiency (EE), were investigated. The morphology of NLCs was observed by transmission electron microscopy. In addition, drug release and antidiabetic activity were also studied. The results revealed that B-NLCs particles were uniformly in the nanosize range and of spherical morphology with a mean size of 92 ± 3.1 nm, a ZP of -31.35 ± 3.08 mV, and an EE of 85.29 ± 3.42%. Baicalin was released from NLCs in a sustained manner. In addition, B-NLCs showed a significantly higher antidiabetic efficacy compared with baicalin. B-NLCs described in this study are well-suited for the delivery of baicalin. Currently, herbal medicines have attracted increasing attention as a complementary approach for type 2 diabetesBaicalin has antihyperglycemic effects by inhibiting lipid peroxidationA suitable formulation is highly desired to overcome the disadvantages (poor solubility and low bioavailability) of baicalinNanostructured lipid carriers could enhance the antidiabetic effects of baicalin. Abbreviations used: B-NLCs: Baicalin-Loaded Nanostructured Lipid Carriers, B-SUS: Baicalin Water Suspension, EE: Encapsulation Efficiency, FBG: Fasting Blood Glucose, HbAlc: Glycosylated Hemoglobin, HPLC: High-performance Liquid Chromatography; NLCs: Nanostructured Lipid Carriers, PI: Polydispersity Index, SD: Sprague-Dawley, SLNs: Solid lipid nanoparticles, STZ

  8. Lipoxin A4 and lipoxin B4 stimulate the release but not the oxygenation of arachidonic acid in human neutrophils: Dissociation between lipid remodeling and adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Nigam, S.; Fiore, S.; Luscinskas, F.W.; Serhan, C.N. (Brigham and Women' s Hospital, Boston, MA (USA))

    1990-06-01

    The profiles of actions of lipoxin A4 (LXA4) and lipoxin B4 (LXB4), two lipoxygenase-derived eicosanoids, were examined with human neutrophils. At nanomolar concentrations, LXA4 and LXB4 each stimulated the release of (1-14C)arachidonic acid from esterified sources in neutrophils. Lipoxin-induced release of (1-14C)arachidonic acid was both dose- and time-dependent and was comparable to that induced by the chemotactic peptide f-met-leu-phe. Time-course studies revealed that lipoxin A4 and lipoxin B4 each induced a biphasic release of (1-14C)arachidonic acid, which was evident within seconds (5-15 sec) in its initial phase and minutes (greater than 30 sec) in the second phase. In contrast, the all-trans isomers of LXA4 and LXB4 did not provoke (1-14C)AA release. Lipoxin-induced release of arachidonic acid was inhibited by prior treatment of the cells with pertussis toxin but not by its beta-oligomers, suggesting the involvement of guaninine nucleotide-binding regulatory proteins in this event. Dual radiolabeling of neutrophil phospholipid classes with (1-14C)arachidonic acid and (3H)palmitic acid showed that phosphatidylcholine was a major source of lipoxin-induced release of (1-14C)arachidonic acid. They also demonstrated that lipoxins rapidly stimulate both formation of phosphatidic acid as well as phospholipid remodeling. Although both LXA4 and LXB4 (10(-8)-10(-6) M) stimulated the release of (1-14C)arachidonic acid, neither compound evoked its oxygenation by either the 5- or 15-lipoxygenase pathways (including the formation of LTB4, 20-COOH-LTB4, 5-HETE, or 15-HETE). LXA4 and LXB4 (10(-7) M) each stimulated the elevation of cytosolic Ca2+ as monitored with Fura 2-loaded cells, albeit to a lesser extent than equimolar concentrations of FMLP. Neither lipoxin altered the binding of (3H)LTB4 to its receptor on neutrophils.

  9. Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Nagelová, Veronika; Tichá, Anežka; Zemenová, Jana; Pirník, Zdenko; Holubová, Martina; Špolcová, Andrea; Mikulášková, Barbora; Blechová, Miroslava; Sýkora, D.; Lacinová, Z.; Haluzík, M.; Železná, Blanka; Kuneš, Jaroslav

    2015-01-01

    Roč. 39, č. 6 (2015), s. 986-993 ISSN 0307-0565 R&D Projects: GA ČR GAP303/10/1368; GA ČR GAP303/12/0576; GA TA ČR(CZ) TE01020028 Institutional support: RVO:61388963 Keywords : food intake * prolactin-releasing peptide * GPR10 receptor Subject RIV: CE - Biochemistry Impact factor: 5.337, year: 2015

  10. Biodegradable Poly(D,L-Lactide)/Lipid Blend Microparticles Prepared by Oil-in-Water Emulsion Method for Controlled Release Drug Delivery

    OpenAIRE

    Yaowalak Srisuwan; Yodthong Baimark

    2014-01-01

    The effects of blend ratio and drug loading content of poly(D,L-lactide) (PDLL)/stearic acid blends on microparticle characteristics and drug release behaviors were evaluated. The blend microparticles were prepared by an oil-in-water emulsion solvent evaporation method for drug delivery of a poorly water-soluble model drug, indomethacin. The microparticles were characterized using a combination of scanning electron microscopy (SEM), light scattering particle size analysis, differential scanni...

  11. Effects of solid-state fermentation with two filamentous fungi on the total phenolic contents, flavonoids, antioxidant activities and lipid fractions of plum fruit (Prunus domestica L.) by-products.

    Science.gov (United States)

    Dulf, Francisc Vasile; Vodnar, Dan Cristian; Socaciu, Carmen

    2016-10-15

    Evolutions of phenolic contents and antioxidant activities during solid-state fermentation (SSF) of plum pomaces (from the juice industry) and brandy distillery wastes with Aspergillus niger and Rhizopus oligosporus were investigated. The effect of fermentation time on the oil content and major lipid classes in the plum kernels was also studied. Results showed that total phenolic (TP) amounts increased by over 30% for SSF with Rhizopus oligosporus and by >21% for SSF with A. niger. The total flavonoid contents presented similar tendencies to those of the TPs. The free radical scavenging activities of methanolic extracts were also significantly enhanced. The HPLC-MS analysis showed that quercetin-3-glucoside was the major phenolic compound in both fermented plum by-products. The results also demonstrated that SSF not only helped to achieve higher lipid recovery from plum kernels, but also resulted in oils with better quality attributes (high sterol ester and n-3 PUFA-rich polar lipid contents). Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Nanostructured lipid carriers versus microemulsions for delivery of the poorly water-soluble drug luteolin.

    Science.gov (United States)

    Liu, Ying; Wang, Lan; Zhao, Yiqing; He, Man; Zhang, Xin; Niu, Mengmeng; Feng, Nianping

    2014-12-10

    Nanostructured lipid carriers and microemulsions effectively deliver poorly water-soluble drugs. However, few studies have investigated their ability and difference in improving drug bioavailability, especially the factors contributed to the difference. Thus, this study was aimed at investigating their efficiency in bioavailability enhancement based on studying two key processes that occur in NLC and ME during traverse along the intestinal tract: the solubilization process and the intestinal permeability process. The nanostructured lipid carriers and microemulsions had the same composition except that the former were prepared with solid lipids and the latter with liquid lipids; both were evaluated for particle size and zeta potential. Transmission electron microscopy, differential scanning calorimetry, and X-ray diffraction were performed to characterize their properties. Furthermore, in vitro drug release, in situ intestinal absorption, and in vitro lipolysis were studied. The bioavailability of luteolin delivered using nanostructured lipid carriers in rats was compared with that delivered using microemulsions and suspensions. The in vitro analysis revealed different release mechanisms for luteolin in nanostructured lipid carriers and microemulsions, although the in situ intestinal absorption was similar. The in vitro lipolysis data indicated that digestion speed and extent were higher for microemulsions than for nanostructured lipid carriers, and that more of the former partitioned to the aqueous phase. The in vivo bioavailability analysis in rats indicated that the oral absorption and bioavailability of luteolin delivered using nanostructured lipid carriers and microemulsions were higher than those of luteolin suspensions. Nanostructured lipid carriers and microemulsions improved luteolin's oral bioavailability in rats. The rapid lipid digestion and much more drug solubilized available for absorption in microemulsions may contribute to better absorption and

  13. Solid phase microextraction as a reliable alternative to conventional extraction techniques to evaluate the pattern of hydrolytically released components in Vitis vinifera L. grapes.

    Science.gov (United States)

    Perestrelo, Rosa; Caldeira, Michael; Câmara, José S

    2012-06-15

    In present research, headspace solid-phase microextraction (HS-SPME) followed by gas chromatography-mass spectrometry (GC-qMS), was evaluated as a reliable and improved alternative to the commonly used liquid-liquid extraction (LLE) technique for the establishment of the pattern of hydrolytically released components of 7 Vitis vinifera L. grape varieties, commonly used to produce the world-famous Madeira wine. Since there is no data available on their glycosidic fractions, at a first step, two hydrolyse procedures, acid and enzymatic, were carried out using Boal grapes as matrix. Several parameters susceptible of influencing the hydrolytic process were studied. The best results, expressed as GC peak area, number of identified components and reproducibility, were obtained using ProZym M with b-glucosidase activity at 35°C for 42h. For the extraction of hydrolytically released components, HS-SPME technique was evaluated as a reliable and improved alternative to the conventional extraction technique, LLE (ethyl acetate). HS-SPME using DVB/CAR/PDMS as coating fiber displayed an extraction capacity two fold higher than LLE (ethyl acetate). The hydrolyzed fraction was mainly characterized by the occurrence of aliphatic and aromatic alcohols, followed by acids, esters, carbonyl compounds, terpenoids, and volatile phenols. Concerning to terpenoids its contribution to the total hydrolyzed fraction is highest for Malvasia Cândida (23%) and Malvasia Roxa (13%), and their presence according previous studies, even at low concentration, is important from a sensorial point of view (can impart floral notes to the wines), due to their low odor threshold (μg/L). According to the obtained data by principal component analysis (PCA), the sensorial properties of Madeira wines produced by Malvasia Cândida and Malvasia Roxa could be improved by hydrolysis procedure, since their hydrolyzed fraction is mainly characterized by terpenoids (e.g. linalool, geraniol) which are responsible

  14. Effects of long-term intraperitoneal injection of thyrotropin-releasing hormone (TRH) on aging- and obesity-related changes in body weight, lipid metabolism, and thyroid functions.

    Science.gov (United States)

    Pierpaoli, Walter; Lesnikov, Vladimir A

    2011-02-01

    Adult adipose mice, high fat diet-fed (HFD) mice, anterior hypothalamus-lesioned obese mice and genetically obese mice, were injected daily with thyrotropin releasing hormone (TRH). The treatment provoked a mobilization of triglycerides in the peripheral blood, a decrease of leptin and a loss of body weight. The weight loss did not depend on TSH-mediated stimulation of thyroid hormone secretion with consequent metabolic hyperthyroidism. The levels of blood cholesterol were not affected or even suppressed. Even at a very high dosage TRH did not affect the obesity of genetically obese mice. The ubiquitous tripeptide TRH may thus constitute a key element in the hormone-controlled regulation of body weight and fat stores in the adult and aging body.

  15. Municipal solid waste compost as a novel sorbent for antimony(V): adsorption and release trials at acidic pH.

    Science.gov (United States)

    Diquattro, Stefania; Garau, Giovanni; Lauro, Gian Paolo; Silvetti, Margherita; Deiana, Salvatore; Castaldi, Paola

    2018-02-01

    The ability of two municipal solid waste composts (MSW-Cs) to sorb antimony(V) in acidic conditions (pH 4.5) was investigated. Sorption isotherms and kinetics showed that both MSW-Cs could sorb antimony(V), even if in different amounts (~ 0.18 and 0.24 mmol g -1 of Sb(V) by MSW-C1 and MSW-C2, respectively). These differences were ascribed to the chemical composition of composts, as well as to the total acidity of their humic substances. The Sb(V) sorption by both MSW-Cs followed a pseudo-second-order kinetic model, while the sorption isotherms data fitted the Freundlich model better than the Langmuir one. The humic acids extracted from composts contributed to 4.26 and 8.24% of Sb(V) sorption by MSW-C1 and MSW-C2 respectively. SEM-EDX spectra of the MSW-C+Sb(V) systems showed a certain association of Ca(II) with Sb(V), while sequential extraction procedures indicated that more than 80% of the Sb(V) sorbed was strongly retained by MSW-Cs. On the other hand, treatment with oxalic acid at pH 4.5 favored the release of more than 98 and 65% of the Sb(V) sorbed by MSW-C1 and MSW-C2 respectively, supporting a possible role of calcium in Sb(V) retention. The results from this study suggest that MSW-Cs could be used as amendments for the in-situ immobilization of Sb(V) in acidic-polluted soils.

  16. 15N and 31P solid-state NMR study of transmembrane domain alignment of M2 protein of influenza A virus in hydrated cylindrical lipid bilayers confined to anodic aluminum oxide nanopores.

    Science.gov (United States)

    Chekmenev, Eduard Y; Hu, Jun; Gor'kov, Peter L; Brey, William W; Cross, Timothy A; Ruuge, Andres; Smirnov, Alex I

    2005-04-01

    This communication reports the first example of a high resolution solid-state 15N 2D PISEMA NMR spectrum of a transmembrane peptide aligned using hydrated cylindrical lipid bilayers formed inside nanoporous anodic aluminum oxide (AAO) substrates. The transmembrane domain SSDPLVVA(A-15N)SIIGILHLILWILDRL of M2 protein from influenza A virus was reconstituted in hydrated 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine bilayers that were macroscopically aligned by a conventional micro slide glass support or by the AAO nanoporous substrate. 15N and 31P NMR spectra demonstrate that both the phospholipids and the protein transmembrane domain are uniformly aligned in the nanopores. Importantly, nanoporous AAO substrates may offer several advantages for membrane protein alignment in solid-state NMR studies compared to conventional methods. Specifically, higher thermal conductivity of aluminum oxide is expected to suppress thermal gradients associated with inhomogeneous radio frequency heating. Another important advantage of the nanoporous AAO substrate is its excellent accessibility to the bilayer surface for exposure to solute molecules. Such high accessibility achieved through the substrate nanochannel network could facilitate a wide range of structure-function studies of membrane proteins by solid-state NMR.

  17. Reducible cationic lipids for gene transfer.

    Science.gov (United States)

    Wetzer, B; Byk, G; Frederic, M; Airiau, M; Blanche, F; Pitard, B; Scherman, D

    2001-01-01

    One of the main challenges of gene therapy remains the increase of gene delivery into eukaryotic cells. We tested whether intracellular DNA release, an essential step for gene transfer, could be facilitated by using reducible cationic DNA-delivery vectors. For this purpose, plasmid DNA was complexed with cationic lipids bearing a disulphide bond. This reduction-sensitive linker is expected to be reduced and cleaved in the reducing milieu of the cytoplasm, thus potentially improving DNA release and consequently transfection. The DNA--disulphide-lipid complexation was monitored by ethidium bromide exclusion, and the size of complexes was determined by dynamic light scattering. It was found that the reduction kinetics of disulphide groups in DNA--lipid complexes depended on the position of the disulphide linker within the lipid molecule. Furthermore, the internal structure of DNA--lipid particles was examined by small-angle X-ray scattering before and after lipid reduction. DNA release from lipid complexes was observed after the reduction of disulphide bonds of several lipids. Cell-transfection experiments suggested that complexes formed with selected reducible lipids resulted in up to 1000-fold higher reporter-gene activity, when compared with their analogues without disulphide bonds. In conclusion, reduction-sensitive groups introduced into cationic lipid backbones potentially allow enhanced DNA release from DNA--lipid complexes after intracellular reduction and represent a tool for improved vectorization. PMID:11389682

  18. Lemon (Citrus limon, Burm.f.) essential oil enhances the trans-epidermal release of lipid-(A, E) and water-(B6, C) soluble vitamins from topical emulsions in reconstructed human epidermis.

    Science.gov (United States)

    Valgimigli, L; Gabbanini, S; Berlini, E; Lucchi, E; Beltramini, C; Bertarelli, Y L

    2012-08-01

    Topical bioavailability of lipid- and water-soluble vitamins is a critical issue for protecting or anti-ageing formulations. Using 17-day-old SkinEthic(®) reconstructed human epidermis, we investigated (at 34°C) the role of lemon EO in enhancing the penetration of α-tocopherol (E) and retinyl acetate (A), pyridoxine (B(6)) and ascorbic acid (C), released from O/W or W/O emulsions. D-limonene, α-pinene and p-cymene (65.9, 2.2 and 0.5%w/w of the oil) had skin permeability coefficients Ps (10(-3) cm h(-1)) of 0.56 ± 0.03 (or 0.73 ± 0.02), 0.72 ± 0.05 (or 0.98 ± 0.05) and 0.84 ± 0.04 (or 1.14 ± 0.04), respectively, when incorporated in a W/O (or O/W) emulsion. Vitamins B6, C and A had Ps values of (3.0 ± 0.4) × 10(-3), (7.9 ± 0.6) × 10(-3) and (0.37 ± 0.02) × 10(-5) cm h(-1), respectively, and their flux through the skin was enhanced by a factor of 4.1, 3.4 and 5.8, respectively, in the presence of lemon EO. The penetration of vitamin E was nine-fold enhanced. Lemon EO produced only reversible modification of TEWL, and it is a safe and effective penetration enhancer for topical administration of lipid- and water-soluble vitamins. © 2012 The Authors. ICS © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  19. Alendronate-Loaded Modified Drug Delivery Lipid Particles Intended for Improved Oral and Topical Administration

    Directory of Open Access Journals (Sweden)

    Lacramioara Ochiuz

    2016-06-01

    Full Text Available The present paper focuses on solid lipid particles (SLPs, described in the literature as the most effective lipid drug delivery systems that have been introduced in the last decades, as they actually combine the advantages of polymeric particles, hydrophilic/lipophilic emulsions and liposomes. In the current study, we present our most recent advances in the preparation of alendronate (AL-loaded SLPs prepared by hot homogenization and ultrasonication using various ratios of a self-emulsifying lipidic mixture of Compritol 888, Gelucire 44/14, and Cremophor A 25. The prepared AL-loaded SLPs were investigated for their physicochemical, morphological and structural characteristics by dynamic light scattering, differential scanning calorimetry, thermogravimetric and powder X-ray diffraction analysis, infrared spectroscopy, optical and scanning electron microscopy. Entrapment efficacy and actual drug content were assessed by a validated HPLC method. In vitro dissolution tests performed in simulated gastro-intestinal fluids and phosphate buffer solution pH 7.4 revealed a prolonged release of AL of 70 h. Additionally, release kinetics analysis showed that both in simulated gastrointestinal fluids and in phosphate buffer solution, AL is released from SLPs based on equal ratios of lipid excipients following zero-order kinetics, which characterizes prolonged-release drug systems.

  20. Lipid somersaults

    DEFF Research Database (Denmark)

    Günther-Pomorski, Thomas; Menon, Anant K.

    2016-01-01

    Membrane lipids diffuse rapidly in the plane of the membrane but their ability to flip spontaneously across a membrane bilayer is hampered by a significant energy barrier. Thus spontaneous flip-flop of polar lipids across membranes is very slow, even though it must occur rapidly to support diverse...... aspects of cellular life. Here we discuss the mechanisms by which rapid flip-flop occurs, and what role lipid flipping plays in membrane homeostasis and cell growth. We focus on conceptual aspects, highlighting mechanistic insights from biochemical and in silico experiments, and the recent, ground......-breaking identification of a number of lipid scramblases....

  1. Stepwise encapsulation and controlled two-stage release system for cis-Diamminediiodoplatinum.

    Science.gov (United States)

    Chen, Yun; Li, Qian; Wu, Qingsheng

    2014-01-01

    cis-Diamminediiodoplatinum (cis-DIDP) is a cisplatin-like anticancer drug with higher anticancer activity, but lower stability and price than cisplatin. In this study, a cis-DIDP carrier system based on micro-sized stearic acid was prepared by an emulsion solvent evaporation method. The maximum drug loading capacity of cis-DIDP-loaded solid lipid nanoparticles was 22.03%, and their encapsulation efficiency was 97.24%. In vitro drug release in phosphate-buffered saline (pH =7.4) at 37.5°C exhibited a unique two-stage process, which could prove beneficial for patients with tumors and malignancies. MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay results showed that cis-DIDP released from cis-DIDP-loaded solid lipid nanoparticles had better inhibition activity than cis-DIDP that had not been loaded.

  2. Pharmacogenetics of lipid diseases

    Directory of Open Access Journals (Sweden)

    Ordovas Jose M

    2004-01-01

    Full Text Available Abstract The genetic basis for most of the rare lipid monogenic disorders have been elucidated, but the challenge remains in determining the combination of genes that contribute to the genetic variability in lipid levels in the general population; this has been estimated to be in the range of 40-60 per cent of the total variability. Therefore, the effect of common polymorphisms on lipid phenotypes will be greatly modulated by gene-gene and gene-environment interactions. This approach can also be used to characterise the individuality of the response to lipid-lowering therapies, whether using drugs (pharmacogenetics or dietary interventions (nutrigenetics. In this regard, multiple studies have already described significant interactions between candidate genes for lipid and drug metabolism that modulate therapeutic response--although the outcomes of these studies have been controversial and call for more rigorous experimental design and analytical approaches. Once solid evidence about the predictive value of genetic panels is obtained, risk and therapeutic algorithms can begin to be generated that should provide an accurate measure of genetic predisposition, as well as targeted behavioural modifications or drugs of choice and personalised dosages of these drugs.

  3. Consumption of a solid fat rich in lauric acid results in a more favorable serum lipid profile in healthy men and women than consumption of a solid fat rich in trans-fatty acids

    NARCIS (Netherlands)

    Roos, de N.M.; Schouten, E.G.; Katan, M.B.

    2001-01-01

    Solid fats are used in food manufacturing to provide texture and firmness to foods. Such fats are rich in either saturated or trans-fatty acids, both of which increase the risk of coronary heart disease. Epidemiological and experimental studies suggest that trans-fatty acids increase risk more than

  4. An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersions prepared via fused deposition modeling (FDM) 3D printing.

    Science.gov (United States)

    Alhijjaj, Muqdad; Belton, Peter; Qi, Sheng

    2016-11-01

    FDM 3D printing has been recently attracted increasing research efforts towards the production of personalized solid oral formulations. However, commercially available FDM printers are extremely limited with regards to the materials that can be processed to few types of thermoplastic polymers, which often may not be pharmaceutically approved materials nor ideal for optimizing dosage form performance of poor soluble compounds. This study explored the use of polymer blends as a formulation strategy to overcome this processability issue and to provide adjustable drug release rates from the printed dispersions. Solid dispersions of felodipine, the model drug, were successfully fabricated using FDM 3D printing with polymer blends of PEG, PEO and Tween 80 with either Eudragit E PO or Soluplus. As PVA is one of most widely used polymers in FDM 3D printing, a PVA based solid dispersion was used as a benchmark to compare the polymer blend systems to in terms of processability. The polymer blends exhibited excellent printability and were suitable for processing using a commercially available FDM 3D printer. With 10% drug loading, all characterization data indicated that the model drug was molecularly dispersed in the matrices. During in vitro dissolution testing, it was clear that the disintegration behavior of the formulations significantly influenced the rates of drug release. Eudragit EPO based blend dispersions showed bulk disintegration; whereas the Soluplus based blends showed the 'peeling' style disintegration of strip-by-strip. The results indicated that interplay of the miscibility between excipients in the blends, the solubility of the materials in the dissolution media and the degree of fusion between the printed strips during FDM process can be used to manipulate the drug release rate of the dispersions. This brings new insight into the design principles of controlled release formulations using FDM 3D printing. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Structured emulsion-based delivery systems: controlling the digestion and release of lipophilic food components.

    Science.gov (United States)

    McClements, David Julian; Li, Yan

    2010-09-15

    There is a need for edible delivery systems to encapsulate, protect and release bioactive and functional lipophilic constituents within the food and pharmaceutical industries. These delivery systems could be used for a number of purposes: controlling lipid bioavailability; targeting the delivery of bioactive components within the gastrointestinal tract; and designing food matrices that delay lipid digestion and induce satiety. Emulsion technology is particularly suited for the design and fabrication of delivery systems for lipids. In this article we provide an overview of a number of emulsion-based technologies that can be used as edible delivery systems by the food and other industries, including conventional emulsions, nanoemulsions, multilayer emulsions, solid lipid particles, and filled hydrogel particles. Each of these delivery systems can be produced from food-grade (GRAS) ingredients (e.g., lipids, proteins, polysaccharides, surfactants, and minerals) using relatively simple processing operations (e.g., mixing, homogenizing, and thermal processing). The structure, preparation, and utilization of each type of delivery system for controlling lipid digestion are discussed. This knowledge can be used to select the most appropriate emulsion-based delivery system for specific applications, such as encapsulation, controlled digestion, and targeted release. Copyright 2010 Elsevier B.V. All rights reserved.

  6. Viability of the microencapsulation of a casein hydrolysate in lipid microparticles of cupuacu butter and stearic acid

    Directory of Open Access Journals (Sweden)

    Samantha Cristina Pinho

    2013-04-01

    Full Text Available Normal 0 21 false false false PT-BR X-NONE X-NONE Solid lipid microparticles produced with a mixture of cupuacu butter and stearic acid were used to microencapsulate a commercial casein hydrolysate (Hyprol 8052. The composition of the lipid matrix used for the production of the lipid microparticles was chosen according to data on the wide angle X-ray diffraction (WAXD and differential scanning calorimetry (DSC of bulk lipid mixtures, which indicated that the presence of 10 % cupuacu butter was sufficient to significantly change the crystalline arrangement of pure stearic acid. Preliminary tests indicated that a minimum proportion of 4 % of surfactant (polysorbate 80 was necessary to produce empty spherical lipid particles with average diameters below 10 mm. The lipid microparticles were produced using 20 % cupuacu butter and 80 % stearic acid and then stabilized with 4 % of polysorbate 80, exhibiting an encapsulation efficiency of approximately 74 % of the casein hydrolysate. The melting temperature of the casein hydrolysate-loaded lipid microparticles was detected at 65.2 °C, demonstrating that the particles were solid at room temperature as expected and indicating that the incorporation of peptides had not affected their thermal behavior. After 25 days of storage, however, there was a release of approximately 30 % of the initial amount of encapsulated casein hydrolysate. This release was not thought to have been caused by the liberation of encapsulated casein hydrolysate. Instead, it was attributed to the possible desorption of the adsorbed peptides present on the surface of the lipid microparticles.

  7. Phase I study of OM-174, a lipid A analogue, with assessment of immunological response, in patients with refractory solid tumors

    International Nuclear Information System (INIS)

    Isambert, Nicolas; Bardou, Marc; Fumoleau, Pierre; Paul, Catherine; Ferrand, Christophe; Zanetta, Sylvie; Bauer, Jacques; Ragot, Kevin; Lizard, Gérard; Jeannin, Jean-François

    2013-01-01

    Lipids A, the lipophilic partial structure of lipopolysaccharides, induce regression of several tumor types in animal models. Rather than exerting direct cytotoxic effect, these compounds trigger the immune system which in turn stimulates secretion of cytokines, and activates the inducible nitric oxide synthase, as well as immune cell infiltration of tumors. OM-174 is an analogue of lipid A with dual action on Toll-like receptors 2 and 4. In an experimental model of peritoneal carcinomatosis induced in BDIX rats by intraperitoneal injection of syngeneic PROb colon cancer cells, it induced a complete regression of tumors. The present phase I trial was conducted to determine the maximum tolerated dose, the recommended phase II dose and biological response associated with OM-174 administered as intravenous infusion. Patients received OM-174 twice weekly for a total of 5, 10 or 15 injections of either 600, 800 or 1000 μg/m 2 . Blood samples for pharmacokinetic analysis and cytokine dosages were collected. NK cells activity and Toll-like receptors 4 polymorphism analysis were also performed. Seventeen patients were included. The highest dose administered was 1000 μg/m 2 repeated in 15 injections. The most common toxicities were a chills, fever, nausea/vomiting, diarrhea, fatigue and headache. No patient experienced haematological side effects. As no dose limiting toxicity was observed, despite a grade 3 respiratory complication, the maximal tolerated dose and recommended dose were not established. Three patients exhibited disease stabilization with a mean duration of 4 months. Pharmacokinetic profile of OM-174 was characterized by a low distribution volume and clearance. Analysis of TLR 4 polymorphysm showed that most (16/17) patients carried the wild type alleles. A progressive increase in NK cell number and activity was observed only in patients receiving 1000 μg/m 2 of OM-174. A peak of IL-8 and IL-10 concentrations were observed after each OM-174 injection. Peaks

  8. Identifying a compound modifying a cellular response, comprises attaching cells having a reporter system onto solid supports, releasing a library member, screening and identifying target cells

    DEFF Research Database (Denmark)

    2011-01-01

    The present invention relates to methods for identifying compounds capable of modulating a cellular response. The methods involve attaching living cells to solid supports comprising a library of test compounds. Test compounds modulating a cellular response, for example via a cell surface molecule...... may be identified by selecting solid supports comprising cells, wherein the cellular response of interest has been modulated. The cellular response may for example be changes in signal transduction pathways modulated by a cell surface molecule....

  9. Mechanical properties and drug release of venlafaxine HCl solid mini matrices prepared by hot-melt extrusion and hot or ambient compression.

    Science.gov (United States)

    Avgerinos, Theodoros; Kantiranis, Nikolaos; Panagopoulou, Athanasia; Malamataris, Stavros; Kachrimanis, Kyriakos; Nikolakakis, Ioannis

    2018-02-01

    Objective/significance: To elucidate the role of plasticizers in different mini matrices and correlate mechanical properties with drug release. Cylindrical pellets were prepared by hot-melt extrusion (HME) and mini tablets by hot (HC) and ambient compression (AC). Venlafaxine HCl was the model drug, Eudragit ® RSPO the matrix former and citric acid or Lutrol ® F127 the plasticizers. The matrices were characterized for morphology, crystallinity, and mechanical properties. The influence of plasticizer's type and content on the extrusion pressure (P e ) during HME and ejection during tableting was examined and the mechanical properties were correlated with drug release parameters. Resistance to extrusion and tablet ejection force were reduced by Lutrol ® F127 which also produced softer and weaker pellets with faster release, but harder and stronger HC tablets with slower release. HME pellets showed greater tensile strength (T) and 100 times slower release than tablets. P e correlated with T and resistance to deformation of the corresponding pellets (r 2  = 0.963 and 0.945). For both HME and HC matrices the decrease of drug release with T followed a single straight line (r 2  = 0.990) and for HME the diffusion coefficient (D e ) and retreat rate constant (k b ) decreased linearly with T (r 2  = 0.934 and 0.972). Lutrol ® F127 and citric acid are efficient plasticizers and Lutrol ® F127 is a thermal binder/lubricant in HC compression. The different bonding mechanisms of the matrices were reflected in the mechanical strength and drug release. Relationships established between T and drug release parameters for HME and HC matrices may be useful during formulation work.

  10. Development of nanostructured lipid carriers containing salicyclic acid for dermal use based on the Quality by Design method.

    Science.gov (United States)

    Kovács, A; Berkó, Sz; Csányi, E; Csóka, I

    2017-03-01

    The aim of our present work was to evaluate the applicability of the Quality by Design (QbD) methodology in the development and optimalization of nanostructured lipid carriers containing salicyclic acid (NLC SA). Within the Quality by Design methology, special emphasis is layed on the adaptation of the initial risk assessment step in order to properly identify the critical material attributes and critical process parameters in formulation development. NLC SA products were formulated by the ultrasonication method using Compritol 888 ATO as solid lipid, Miglyol 812 as liquid lipid and Cremophor RH 60® as surfactant. LeanQbD Software and StatSoft. Inc. Statistica for Windows 11 were employed to indentify the risks. Three highly critical quality attributes (CQAs) for NLC SA were identified, namely particle size, particle size distribution and aggregation. Five attributes of medium influence were identified, including dissolution rate, dissolution efficiency, pH, lipid solubility of the active pharmaceutical ingredient (API) and entrapment efficiency. Three critical material attributes (CMA) and critical process parameters (CPP) were identified: surfactant concentration, solid lipid/liquid lipid ratio and ultrasonication time. The CMAs and CPPs are considered as independent variables and the CQAs are defined as dependent variables. The 2 3 factorial design was used to evaluate the role of the independent and dependent variables. Based on our experiments, an optimal formulation can be obtained when the surfactant concentration is set to 5%, the solid lipid/liquid lipid ratio is 7:3 and ultrasonication time is 20min. The optimal NLC SA showed narrow size distribution (0.857±0.014) with a mean particle size of 114±2.64nm. The NLC SA product showed a significantly higher in vitro drug release compared to the micro-particle reference preparation containing salicylic acid (MP SA). Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Carbon-Based Solid-State Calcium Ion-Selective Microelectrode and Scanning Electrochemical Microscopy: A Quantitative Study of pH-Dependent Release of Calcium Ions from Bioactive Glass.

    Science.gov (United States)

    Ummadi, Jyothir Ganesh; Downs, Corey J; Joshi, Vrushali S; Ferracane, Jack L; Koley, Dipankar

    2016-03-15

    Solid-state ion-selective electrodes are used as scanning electrochemical microscope (SECM) probes because of their inherent fast response time and ease of miniaturization. In this study, we report the development of a solid-state, low-poly(vinyl chloride), carbon-based calcium ion-selective microelectrode (Ca(2+)-ISME), 25 μm in diameter, capable of performing an amperometric approach curve and serving as a potentiometric sensor. The Ca(2+)-ISME has a broad linear response range of 5 μM to 200 mM with a near Nernstian slope of 28 mV/log[a(Ca(2+))]. The calculated detection limit for Ca(2+)-ISME is 1 μM. The selectivity coefficients of this Ca(2+)-ISME are log K(Ca(2+),A) = -5.88, -5.54, and -6.31 for Mg(2+), Na(+), and K(+), respectively. We used this new type of Ca(2+)-ISME as an SECM probe to quantitatively map the chemical microenvironment produced by a model substrate, bioactive glass (BAG). In acidic conditions (pH 4.5), BAG was found to increase the calcium ion concentration from 0.7 mM ([Ca(2+)] in artificial saliva) to 1.4 mM at 20 μm above the surface. In addition, a solid-state dual SECM pH probe was used to correlate the release of calcium ions with the change in local pH. Three-dimensional pH and calcium ion distribution mapping were also obtained by using these solid-state probes. The quantitative mapping of pH and Ca(2+) above the BAG elucidates the effectiveness of BAG in neutralizing and releasing calcium ions in acidic conditions.

  12. A novel co-processed directly compressible release-retarding polymer: In vitro, solid state and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Prashant Kumar Choudhari

    2018-06-01

    Full Text Available Directly compressible (DC co-processed excipient capable of providing nearly zero order release with improved functionality was developed without any chemical modification by employed various techniques such as physical mixing, high shear mixer granulation and spray drying. Co-processed excipient was developed by using release retarding polymer Eudragit RSPO, separately, in combination with different concentration of hydroxyl propyl methyl cellulose 100 cps (Methocel K100 LV, HPMC, ethyl cellulose (Ethocel N50, EC and hydroxyl propyl cellulose (Klucel EF, HPC. All co-processed excipients were evaluated for their flow properties in terms of angle of repose, bulk density, tapped density, compressibility index and Hausner's ratio. Out of eighteen combinations, the nine co-processed excipients exhibited promising flow properties were found suitable for direct compression and formulated as tablets. Metoprolol succinate, a BCS Class I drug, was selected as a model drug and the formulation was developed employing direct compression approach. The developed tablets were evaluated for physical parameters like uniformity of weight, thickness, hardness, friability and assay. In vitro dissolution study confirms that formulation prepared using co-processed excipient showed sustained drug release. The optimized tablet formulation was characterized by DSC, FTIR and PXRD which confirms the absence of any chemical change during co-processing. The optimized formulation was kept for stability study for six months as per ICH guidelines and found to be stable. In vivo pharmacokinetic study of optimized formulation in rats showed similar pharmacokinetic behaviour as was observed with the marketed brand. Study revealed that co-processed excipient has advantage over polymers with single property and can be utilised for sustained release formulation. Keywords: Co-processed excipient, Metoprolol succinate, Extended-release, Direct compression, Zero-order release

  13. Lipid Nanotechnology

    Directory of Open Access Journals (Sweden)

    Gijsje Koenderink

    2013-02-01

    Full Text Available Nanotechnology is a multidisciplinary field that covers a vast and diverse array of devices and machines derived from engineering, physics, materials science, chemistry and biology. These devices have found applications in biomedical sciences, such as targeted drug delivery, bio-imaging, sensing and diagnosis of pathologies at early stages. In these applications, nano-devices typically interface with the plasma membrane of cells. On the other hand, naturally occurring nanostructures in biology have been a source of inspiration for new nanotechnological designs and hybrid nanostructures made of biological and non-biological, organic and inorganic building blocks. Lipids, with their amphiphilicity, diversity of head and tail chemistry, and antifouling properties that block nonspecific binding to lipid-coated surfaces, provide a powerful toolbox for nanotechnology. This review discusses the progress in the emerging field of lipid nanotechnology.

  14. Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability

    Directory of Open Access Journals (Sweden)

    Neves AR

    2013-01-01

    structure conferred by the inclusion of the liquid lipid, since they had lower values for phase transition temperature, melting enthalpy, and the recrystallization index. The presence of resveratrol induced a disorder in the crystal structure of the nanoparticles, suggesting a favoring of its entrapment. The in vitro release studies on conditions of storage showed a negligible resveratrol release over several hours for both nanosystems and the in vitro simulation of gastrointestinal transit showed that the resveratrol remained mostly associated with the lipid nanoparticles after their incubation in digestive fluids.Conclusion: Both nanodelivery systems can be considered suitable carriers for oral administration, conferring protection to the incorporated resveratrol and allowing a controlled release after uptake.Keywords: nanodelivery systems, solid lipid nanoparticles, nanostructured lipid carriers, polyphenol

  15. Development of In Vitro-In Vivo Correlation for Amorphous Solid Dispersion Immediate-Release Suvorexant Tablets and Application to Clinically Relevant Dissolution Specifications and In-Process Controls.

    Science.gov (United States)

    Kesisoglou, Filippos; Hermans, Andre; Neu, Colleen; Yee, Ka Lai; Palcza, John; Miller, Jessica

    2015-09-01

    Although in vitro-in vivo correlations (IVIVCs) are commonly pursued for modified-release products, there are limited reports of successful IVIVCs for immediate-release (IR) formulations. This manuscript details the development of a Multiple Level C IVIVC for the amorphous solid dispersion formulation of suvorexant, a BCS class II compound, and its application to establishing dissolution specifications and in-process controls. Four different 40 mg batches were manufactured at different tablet hardnesses to produce distinct dissolution profiles. These batches were evaluated in a relative bioavailability clinical study in healthy volunteers. Although no differences were observed for the total exposure (AUC) of the different batches, a clear relationship between dissolution and Cmax was observed. A validated Multiple Level C IVIVC against Cmax was developed for the 10, 15, 20, 30, and 45 min dissolution time points and the tablet disintegration time. The relationship established between tablet tensile strength and dissolution was subsequently used to inform suitable tablet hardness ranges within acceptable Cmax limits. This is the first published report for a validated Multiple Level C IVIVC for an IR solid dispersion formulation demonstrating how this approach can facilitate Quality by Design in formulation development and help toward clinically relevant specifications and in-process controls. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Lipid Panel

    Science.gov (United States)

    ... A routine cardiac risk assessment typically includes a fasting lipid panel. Beyond that, research continues into the usefulness of other non-traditional markers of cardiac risk, such as Lp-PLA 2 . A health practitioner may choose to evaluate one or more ...

  17. Microemulsion extrusion technique : a new method to produce lipid nanoparticles

    NARCIS (Netherlands)

    de Jesus, Marcelo Bispo; Radaic, Allan; Zuhorn, Inge S.; de Paula, Eneida

    2013-01-01

    Solid lipid nanoparticles (SLN) and nano-structured lipid carriers (NLC) have been intensively investigated for different applications, including their use as drug and gene delivery systems. Different techniques have been employed to produce lipid nanoparticles, of which high pressure homogenization

  18. LipidPedia: a comprehensive lipid knowledgebase.

    Science.gov (United States)

    Kuo, Tien-Chueh; Tseng, Yufeng Jane

    2018-04-10

    Lipids are divided into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, sterols, prenol lipids and polyketides. Fatty acyls and glycerolipids are commonly used as energy storage, whereas glycerophospholipids, sphingolipids, sterols and saccharolipids are common used as components of cell membranes. Lipids in fatty acyls, glycerophospholipids, sphingolipids and sterols classes play important roles in signaling. Although more than 36 million lipids can be identified or computationally generated, no single lipid database provides comprehensive information on lipids. Furthermore, the complex systematic or common names of lipids make the discovery of related information challenging. Here, we present LipidPedia, a comprehensive lipid knowledgebase. The content of this database is derived from integrating annotation data with full-text mining of 3,923 lipids and more than 400,000 annotations of associated diseases, pathways, functions, and locations that are essential for interpreting lipid functions and mechanisms from over 1,400,000 scientific publications. Each lipid in LipidPedia also has its own entry containing a text summary curated from the most frequently cited diseases, pathways, genes, locations, functions, lipids and experimental models in the biomedical literature. LipidPedia aims to provide an overall synopsis of lipids to summarize lipid annotations and provide a detailed listing of references for understanding complex lipid functions and mechanisms. LipidPedia is available at http://lipidpedia.cmdm.tw. yjtseng@csie.ntu.edu.tw. Supplementary data are available at Bioinformatics online.

  19. Nanostructured Lipid Carriers (NLC) as Vehicles for Topical Administration of Sesamol: In Vitro Percutaneous Absorption Study and Evaluation of Antioxidant Activity.

    Science.gov (United States)

    Puglia, Carmelo; Lauro, Maria Rosaria; Offerta, Alessia; Crascì, Lucia; Micicchè, Lucia; Panico, Anna Maria; Bonina, Francesco; Puglisi, Giovanni

    2017-03-01

    Sesamol is a natural phenolic compound extracted from Sesamum indicum seed oil. Sesamol is endowed with several beneficial effects, but its use as a topical agent is strongly compromised by unfavorable chemical-physical properties. Therefore, to improve its characteristics, the aim of the present work was the formulation of nanostructured lipid carriers as drug delivery systems for topical administration of sesamol.Two different nanostructured lipid carrier systems have been produced based on the same solid lipid (Compritol® 888 ATO) but in a mixture with two different kinds of oil phase such as Miglyol® 812 (nanostructured lipid carrier-M) and sesame oil (nanostructured lipid carrier-PLUS). Morphology and dimensional distribution of nanostructured lipid carriers have been characterized by differential scanning calorimetry and photon correlation spectroscopy, respectively. The release pattern of sesamol from nanostructured lipid carriers was evaluated in vitro determining drug percutaneous absorption through excised human skin. Furthermore, an oxygen radical absorbance capacity assay was used to determine their antioxidant activity.From the results obtained, the method used to formulate nanostructured lipid carriers led to a homogeneous dispersion of particles in a nanometric range. Sesamol has been encapsulated efficiently in both nanostructured lipid carriers, with higher encapsulation efficiency values (> 90 %) when sesame oil was used as the oil phase (nanostructured lipid carrier-PLUS). In vitro evidences show that nanostructured lipid carrier dispersions were able to control the rate of sesamol diffusion through the skin, with respect to the reference formulations.Furthermore, the oxygen radical absorbance capacity assay pointed out an interesting and prolonged antioxidant activity of sesamol, especially when vehiculated by nanostructured lipid carrier-PLUS. Georg Thieme Verlag KG Stuttgart · New York.

  20. Lipid nanocarriers containing sorafenib inhibit colonies formation in human hepatocarcinoma cells.

    Science.gov (United States)

    Bondì, Maria Luisa; Botto, Chiara; Amore, Erika; Emma, Maria Rita; Augello, Giuseppa; Craparo, Emanuela Fabiola; Cervello, Melchiorre

    2015-09-30

    Here, the potential of two nanostructured lipid carriers (NLC) for controlled release of sorafenib was evaluated. The obtained systems showed characteristics suitable as drug delivery systems for the treatment of hepatocellular carcinoma (HCC) through parenteral administration. The use of a mixture between a solid lipid (tripalmitin) with a liquid lipid (Captex 355 EP/NF or Miglyol 812) to prepare NLC systems could give a higher drug loading capacity and a longer term stability during storage than that obtained by using only solid lipids. The obtained nanoparticles showed a nanometer size and high negative zeta potential values. Scansion electron microscopy (SEM) of the sorafenib loaded NLC revealed a spherical shape with a diameter <300 nm. In vitro biological studies demonstrated that sorafenib loaded into NLC had enhanced anti-tumor activity compared to that of free drug. This finding raises hope in terms of future drug delivery strategy of sorafenib loaded NLC, that can be useful for therapeutic application in HCC. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Triggered Release from Polymer Capsules

    Energy Technology Data Exchange (ETDEWEB)

    Esser-Kahn, Aaron P. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Odom, Susan A. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Sottos, Nancy R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Materials Science and Engineering; White, Scott R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Aerospace Engineering; Moore, Jeffrey S. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry

    2011-07-06

    Stimuli-responsive capsules are of interest in drug delivery, fragrance release, food preservation, and self-healing materials. Many methods are used to trigger the release of encapsulated contents. Here we highlight mechanisms for the controlled release of encapsulated cargo that utilize chemical reactions occurring in solid polymeric shell walls. Triggering mechanisms responsible for covalent bond cleavage that result in the release of capsule contents include chemical, biological, light, thermal, magnetic, and electrical stimuli. We present methods for encapsulation and release, triggering methods, and mechanisms and conclude with our opinions on interesting obstacles for chemically induced activation with relevance for controlled release.

  2. Applications and limitations of lipid nanoparticles in dermal and transdermal drug delivery via the follicular route.

    Science.gov (United States)

    Lauterbach, Andreas; Müller-Goymann, Christel C

    2015-11-01

    Lipid nanoparticles (LN) such as solid lipid nanoparticles (SLN) and nanolipid carriers (NLC) feature several claimed benefits for topical drug therapy including biocompatible ingredients, drug release modification, adhesion to the skin, and film formation with subsequent hydration of the superficial skin layers. However, penetration and permeation into and across deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). As different kinds of nanoparticles provide the potential for penetration into hair follicles (HF) LN are applicable drug delivery systems (DDS) for this route in order to enhance the dermal and transdermal bioavailability of active pharmaceutical ingredients (API). Therefore, this review addresses the HF as application site, published formulations of LN which showed follicular penetration (FP), and characterization methods in order to identify and quantify the accumulation of API delivered by the LN in the HF. Since LN are based on lipids that appear in human sebum which is the predominant medium in HF an increased localization of the colloidal carriers as well as a promoted drug release may be assumed. Therefore, sebum-like lipid material and a size of less or equal 640 nm are appropriate specifications for FP of particulate formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. On the phenomenon of the fast release of energy in irradiated solid methane: discussion of models considering the local space distribution of energy

    International Nuclear Information System (INIS)

    Shabalin, E.P.

    1995-01-01

    A general idea of the phenomenon, so-called 'a burp', is provided. It is concluded that no justified and consistent theory of the burp phenomenon is proposed. The paper expresses criticism on the application of the classic theory of homogeneous chemical reactions and of thermal explosion to analyze burps as it was in common usage up to now. Two hypotheses to explain features burps display are presented instead. Both of them have to do with mechanism of storing and releasing energy accounting for local non-uniformity of temperature end energy deposition. 11 refs., 4 figs

  4. Electrosprayed nanoparticle delivery system for controlled release

    Energy Technology Data Exchange (ETDEWEB)

    Eltayeb, Megdi, E-mail: megdi.eltayeb@sustech.edu [Department of Biomedical Engineering, Sudan University of Science and Technology, PO Box 407, Khartoum (Sudan); Stride, Eleanor, E-mail: eleanor.stride@eng.ox.ac.uk [Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Old Road Campus Research Building, Headington OX3 7DQ (United Kingdom); Edirisinghe, Mohan, E-mail: m.edirisinghe@ucl.ac.uk [Department of Mechanical Engineering, University College London, Torrington Place, London WC1E 7JE (United Kingdom); Harker, Anthony, E-mail: a.harker@ucl.ac.uk [London Centre for Nanotechnology, Gordon Street, London WC1H 0AH (United Kingdom); Department of Physics & Astronomy, University College London, Gower Street, London WC1E 6BT (United Kingdom)

    2016-09-01

    This study utilises an electrohydrodynamic technique to prepare core-shell lipid nanoparticles with a tunable size and high active ingredient loading capacity, encapsulation efficiency and controlled release. Using stearic acid and ethylvanillin as model shell and active ingredients respectively, we identify the processing conditions and ratios of lipid:ethylvanillin required to form nanoparticles. Nanoparticles with a mean size ranging from 60 to 70 nm at the rate of 1.37 × 10{sup 9} nanoparticles per minute were prepared with different lipid:ethylvanillin ratios. The polydispersity index was ≈ 21% and the encapsulation efficiency ≈ 70%. It was found that the rate of ethylvanillin release was a function of the nanoparticle size, and lipid:ethylvanillin ratio. The internal structure of the lipid nanoparticles was studied by transmission electron microscopy which confirmed that the ethylvanillin was encapsulated within a stearic acid shell. Fourier transform infrared spectroscopy analysis indicated that the ethylvanillin had not been affected. Extensive analysis of the release of ethylvanillin was performed using several existing models and a new diffusive release model incorporating a tanh function. The results were consistent with a core-shell structure. - Highlights: • Electrohydrodynamic spraying is used to produce lipid-coated nanoparticles. • A new model is proposed for the release rates of active components from nanoparticles. • The technique has potential applications in food science and medicine. • Electrohydrodynamic processing controlled release lipid nanoparticles.

  5. Lipid nanoparticles (SLN & NLC) for delivery of vitamin E: a comprehensive review.

    Science.gov (United States)

    Saez, V; Souza, I D L; Mansur, C R E

    2018-04-01

    The antioxidative and photoprotective properties of vitamin E have caused it to be included as an active agent in various pharmaceutical and cosmetic products. However, its lipophilicity, chemical instability and poor skin penetration have limited the effectiveness of these formulations. For that reason, many attempts to include it in different drug delivery systems have been made. In recent decades, lipid nanoparticles have received special attention due to their advantages of compatibility with the skin, ability to enhance penetration of drugs in the stratum corneum, protection of the encapsulated substance against degradation induced by the external medium and control of drug release. This work reviews the current status of the encapsulation of vitamin E in lipid nanoparticles. We describe the most important methods for obtaining and characterizing lipid nanoparticles containing vitamin E (LNP-VE), various techniques for the evaluation of vitamin E's properties after encapsulation, the main in vitro and in vivo studies of the potential effectiveness or toxicity of LNP-VE, the formulations and stability studies of this delivery system, the commercial products based on LNP-VE and the regulatory aspects related to lipid nanoparticles. Finally, we discuss the most relevant advantages of encapsulating vitamin E in such particles and critical aspects that still demand attention to enhance the potential of solid lipid nanoparticles to deliver vitamin E. © 2018 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  6. Beyond liposomes: Recent advances on lipid based nanostructures for poorly soluble/poorly permeable drug delivery.

    Science.gov (United States)

    Teixeira, M C; Carbone, C; Souto, E B

    2017-10-01

    Solid lipid nanoparticle (SLN), nanostructured lipid carriers (NLC) and hybrid nanoparticles, have gained increasing interest as drug delivery systems because of their potential to load and release drugs from the Biopharmaceutical classification system (BCS) of class II (low solubility and high permeability) and of class IV (low solubility and low permeability). Lipid properties (e.g. high solubilizing potential, biocompatibility, biotolerability, biodegradability and distinct route of absorption) contribute for the improvement of the bioavailability of these drugs for a set of administration routes. Their interest continues to grow, as translated by the number of patents being field worldwide. This paper discusses the recent advances on the use of SLN, NLC and lipid-polymer hybrid nanoparticles for the loading of lipophilic, poorly water-soluble and poorly permeable drugs, being developed for oral, topical, parenteral and ocular administration, also discussing the industrial applications of these systems. A review of the patents filled between 2014 and 2017, concerning the original inventions of lipid nanocarriers, is also provided. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Implications of formulation design on lipid-based nanostructured carrier system for drug delivery to brain.

    Science.gov (United States)

    Salunkhe, Sachin S; Bhatia, Neela M; Bhatia, Manish S

    2016-05-01

    The aim of present investigation was to formulate and develop lipid-based nanostructured carriers (NLCs) containing Idebenone (IDE) for delivery to brain. Attempts have been made to evaluate IDE NLCs for its pharmacokinetic and pharmacodynamic profile through the objective of enhancement in bioavailability and effectivity of drug. Nanoprecipitation technique was used for development of drug loaded NLCs. The components solid lipid Precirol ATO 5, oil Miglyol 840, surfactants Tween 80 and Labrasol have been screened out for formulation development by consideration of preformulation parameters including solubility, Required Hydrophilic lipophilic balance (HLB) of lipids and stability study. Developed IDE NLCs were subjected for particle size, zeta potential, entrapment efficiency (%EE), crystallographic investigation, transmission electron microscopy, in vitro drug release, pharmacokinetics, in vivo and stability study. Formulation under investigation has particle size 174.1 ± 2.6 nm, zeta potential -18.65 ± 1.13 mV and% EE 90.68 ± 2.90. Crystallographic studies exemplified for partial amorphization of IDE by molecularly dispersion within lipid crust. IDE NLCs showed drug release 93.56 ± 0.39% at end of 24 h by following Higuchi model which necessitates for appropriate drug delivery with enhancement in bioavailability of drug by 4.6-fold in plasma and 2.8-fold in brain over plain drug loaded aqueous dispersions. In vivo studies revealed that effect of drug was enhanced by prepared lipid nanocarriers. IDE lipid-based nanostructured carriers could have potential for efficient drug delivery to brain with enhancement in bioavailability of drug over the conventional formulations.

  8. Releasing metal catalysts via phase transition: (NiO)0.05-(SrTi0.8Nb0.2O3)0.95 as a redox stable anode material for solid oxide fuel cells.

    Science.gov (United States)

    Xiao, Guoliang; Wang, Siwei; Lin, Ye; Zhang, Yanxiang; An, Ke; Chen, Fanglin

    2014-11-26

    Donor-doped perovskite-type SrTiO3 experiences stoichiometric changes at high temperatures in different Po2 involving the formation of Sr or Ti-rich impurities. NiO is incorporated into the stoichiometric strontium titanate, SrTi0.8Nb0.2O3-δ (STN), to form an A-site deficient perovskite material, (NiO)0.05-(SrTi0.8Nb0.2O3)0.95 (Ni-STN), for balancing the phase transition. Metallic Ni nanoparticles can be released upon reduction instead of forming undesired secondary phases. This material design introduces a simple catalytic modification method with good compositional control of the ceramic backbones, by which transport property and durability of solid oxide fuel cell anodes are largely determined. Using Ni-STN as anodes for solid oxide fuel cells, enhanced catalytic activity and remarkable stability in redox cycling have been achieved. Electrolyte-supported cells with the cell configuration of Ni-STN-SDC anode, La0.8Sr0.2Ga0.87Mg0.13O3 (LSGM) electrolyte, and La0.6Sr0.4Co0.2Fe0.8O3 (LSCF) cathode produce peak power densities of 612, 794, and 922 mW cm(-2) at 800, 850, and 900 °C, respectively, using H2 as the fuel and air as the oxidant. Minor degradation in fuel cell performance resulted from redox cycling can be recovered upon operating the fuel cells in H2. Such property makes Ni-STN a promising regenerative anode candidate for solid oxide fuel cells.

  9. How "lucky" we are that the Fukushima disaster occurred in early spring: predictions on the contamination levels from various fission products released from the accident and updates on the risk assessment for solid and thyroid cancers.

    Science.gov (United States)

    Evangeliou, Nikolaos; Balkanski, Yves; Cozic, Anne; Møller, Anders Pape

    2014-12-01

    The present paper studies how a random event (earthquake) and the subsequent disaster in Japan affect transport and deposition of fallout and the resulting health consequences. Therefore, except for the original accident in March 2011, three additional scenarios are assessed assuming that the same releases took place in winter 2010, summer 2011 and autumn 2011 in order to cover a full range of annual seasonality. This is also the first study where a large number of fission products released from the accident are used to assess health risks with the maximum possible efficiency. Xenon-133 and (137)Cs are directly estimated within the model, whereas 15 other radionuclides are calculated indirectly using reported isotopic ratios. As much as 85% of the released (137)Cs would be deposited in continental regions worldwide if the accident occurred in winter 2010, 22% in spring 2011 (when it actually happened), 55% in summer 2011 and 48% if it occurred during autumn 2011. Solid cancer incidents and mortalities from Fukushima are estimated to be between 160 and 880 and from 110 to 640 close to previous estimations. By adding thyroid cancers, the total number rises from 230 to 850 for incidents and from 120 to 650 for mortalities. Fatalities due to worker exposure and mandatory evacuation have been reported to be around 610 increasing total estimated mortalities to 730-1260. These estimates are 2.8 times higher than previously reported ones for radiocaesium and (131)I and 16% higher than those reported based on radiocaesium only. Total expected fatalities from Fukushima are 32% lower than in the winter scenario, 5% that in the summer scenario and 30% lower than in the autumn scenario. Nevertheless, cancer fatalities are expected to be less than 5% of those from the tsunami (~20,000). Copyright © 2014 Elsevier B.V. All rights reserved.

  10. In vitro dissolution of generic immediate-release solid oral dosage forms containing BCS class I drugs: comparative assessment of metronidazole, zidovudine, and amoxicillin versus relevant comparator pharmaceutical products in South Africa and India.

    Science.gov (United States)

    Reddy, Nallagundla H S; Patnala, Srinivas; Löbenberg, Raimar; Kanfer, Isadore

    2014-10-01

    Biowaivers are recommended for immediate-release solid oral dosage forms using dissolution testing as a surrogate for in vivo bioequivalence studies. Several guidance are currently available (the World Health Organization (WHO), the US FDA, and the EMEA) where the conditions are described. In this study, definitions, criteria, and methodologies according to the WHO have been applied. The dissolution performances of immediate-release metronidazole, zidovudine, and amoxicillin products purchased in South African and Indian markets were compared to the relevant comparator pharmaceutical product (CPP)/reference product. The dissolution performances were studied using US Pharmacopeia (USP) apparatus 2 (paddle) set at 75 rpm in each of three dissolution media (pH1.2, 4.5, and 6.8). Concentrations of metronidazole, zidovudine, and amoxicillin in each dissolution media were determined by HPLC. Of the 11 metronidazole products tested, only 8 could be considered as very rapidly dissolving products as defined by the WHO, whereas 2 of those products could be considered as rapidly dissolving products but did not comply with the f 2 acceptance criteria in pH 6.8. All 11 zidovudine products were very rapidly dissolving, whereas in the case of the 14 amoxicillin products tested, none of those products met any of the WHO criteria. This study indicates that not all generic products containing the same biopharmaceutics classification system (BCS) I drug and in similar strength and dosage form are necessarily in vitro equivalent. Hence, there is a need for ongoing market surveillance to determine whether marketed generic products containing BCS I drugs meet the release requirements to confirm their in vitro bioequivalence to the respective reference product.

  11. Dominant portion of thyrotropin-releasing hormone receptor is excluded from lipid domains. Detergent-resistant and detergent-sensitive pools of TRH receptor and Gq alpha/G11 alpha protein

    Czech Academy of Sciences Publication Activity Database

    Rudajev, Vladimír; Novotný, Jiří; Hejnová, Lucie; Milligan, G.; Svoboda, Petr

    2005-01-01

    Roč. 138, č. 2 (2005), s. 111-125 ISSN 0021-924X R&D Projects: GA MŠk(CZ) LC554 Grant - others:GA-(GB) Wellcome Trust Institutional research plan: CEZ:AV0Z50110509 Keywords : TRH receptor * lipid domains * trimeric G proteins Subject RIV: CE - Biochemistry Impact factor: 1.827, year: 2005

  12. Preparation and Characterization of Minoxidil Loaded Nanostructured Lipid Carriers.

    Science.gov (United States)

    Wang, Wenxi; Chen, Lina; Huang, Xinyan; Shao, Anna

    2017-02-01

    Nanostructured lipid carriers (NLCs) are interesting delivery systems for enhancing the penetration of an active substance through the skin after topical administration. The present paper described the development of a novel NLCs for minoxidil (MXD) topical delivery. Stearic acid and oleic acid that showed the highest solubility for MXD were selected as solid lipid and liquid lipid, respectively, and the NLCs were prepared by hot high pressure homogenization method. The minoxidil loaded NLCs prepared accordingly to the optimal formulation exhibited spherical shape with a mean diameter of 281.4 ± 7.4 nm, polydispersity of 0.207 ± 0.009, zeta potential of -32.90 ± 1.23 mV, drug entrapment efficiency of 92.48 ± 0.31%, and drug loading of 13.85 ± 0.47%. Storage stability studies demonstrated that the particle size and entrapment efficiency of the MXD-NLCs were not changed during 3 months both at 4°C and room temperature. Moreover, the release of MXD from the NLCs was faster than drug release from SLNs. In vitro skin permeability test demonstrated that MXD-NLCs had a more pronounced permeation and retention profile than MXD-SLNs. Furthermore, no erythema was observed after administration of MXD-NLCs. All these results indicated that the developed MXD-NLCs could be a promising and effective nanocarrier for topical delivery of MXD.

  13. Development of a validated UPLC method for simultaneous estimation of both free and entrapped (in solid lipid nanoparticles) all-trans retinoic acid and cholecalciferol (vitamin D3) and its pharmacokinetic applicability in rats.

    Science.gov (United States)

    Kumar, Manoj; Sharma, Gaurav; Singla, Dinesh; Singh, Sukhjeet; Sahwney, Sudhir; Chauhan, Anurag S; Singh, Gagandeep; Kaur, Indu Pal

    2014-03-01

    A sensitive ultra-performance liquid chromatography (UPLC) method was developed for simultaneous estimation of all-trans retinoic acid (ATRA) and cholecalciferol (vitamin D3) in rat plasma. The method was validated over the linear range of 1.0-5000ng/ml (r(2)=0.999) for both vitamins with a limit of detection of 0.5ng/ml. Chromatographic separation was achieved using liquid-liquid extraction (LLE) on an Acquity BEH RP 18 column (2.1mm×50mm, I.D. 1.7μm), with mobile phase comprising of acetonitrile:methanol:water (90:8:2, v/v/v), at a flow rate of 0.20ml/min and a total run time of 5min. Intra and inter-day variability (RSD) was ≤3.1%, and the accuracy varied between 95.4-99.9% and 95.3-101.1% respectively, for ATRA and 98.5-100.8% and 99.3-101.7%, respectively for vitamin D3. High recovery of ≥96.0% for ATRA and ≥87.80% for vitamin D3 was achieved. ATRA and vitamin D3 were stable in plasma under different storage and processing conditions. The method was applied to estimate the total drug content and entrapment efficiency of ATRA and vitamin D3 loaded solid lipid nanoparticles (SLNs). Concentration of these two agents was determined in rat plasma after simultaneous subcutaneous administration in free form or when loaded into SLNs thus establishing pharmacokinetic application of the developed procedure. Results indicated an improvement in AUC0-∞ by 5.4 times and 29.4 times for ATRA and vitamin D3, respectively, upon their incorporation into SLNs. Simultaneous administration of these two vitamins and their improved and prolonged bioavailability has scope for their use in treatment and control of tuberculosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Utilisation of solid waste

    Energy Technology Data Exchange (ETDEWEB)

    Balu, K

    1978-07-01

    The prime solution to the present energy crisis is the recovery of latent energy from waste materials, for solid waste contains recoverable energy and it merely needs to be released. The paper is concerned with classification of solid waste, energy content of waste, methods of solid waste disposal, and chemical processing of solid waste. Waste disposal must be performed in situ with energy recovery. Scarcity of available land, pollution problem, and unrecovered latent energy restrict the use of the land-filling method. Pyrolysis is an effective method for the energy recovery and disposal problems. Chemical processing is suitable for the separated cellulosic fraction of the waste material.

  15. A Dansyl Fluorescence-Based Assay for Monitoring Kinetics of Lipid Extraction and Transfer

    Science.gov (United States)

    Ran, Yong

    2008-01-01

    Lipid transfer proteins (LTPs) play important roles in cellular biology, and fluorescence spectroscopy has found wide range use as a facile means for time-resolved monitoring of protein-lipid interactions[1]. Here, we show how the fluorescence emission properties of dansyl-DHPE can be exploited to characterize lipid extraction and lipid transfer kinetics. The GM2 activator protein serves as an example LTP where the ability to independently characterize lipid extraction from donor vesicles, formation of a protein:lipid complex in solution, and release of lipid from the complex to acceptor liposomes is crucial for full kinetic characterization of lipid transfer. PMID:18694718

  16. Lipid Configurations from Molecular Dynamics Simulations

    DEFF Research Database (Denmark)

    Pezeshkian, Weria; Khandelia, Himanshu; Marsh, Derek

    2018-01-01

    of dihedral angles in palmitoyl-oleoyl phosphatidylcholine from molecular dynamics simulations of hydrated fluid bilayer membranes. We compare results from the widely used lipid force field of Berger et al. with those from the most recent C36 release of the CHARMM force field for lipids. Only the CHARMM force......The extent to which current force fields faithfully reproduce conformational properties of lipids in bilayer membranes, and whether these reflect the structural principles established for phospholipids in bilayer crystals, are central to biomembrane simulations. We determine the distribution...

  17. Optimization of pineapple pulp residue hydrolysis for lipid production by Rhodotorula glutinis TISTR5159 using as biodiesel feedstock.

    Science.gov (United States)

    Tinoi, Jidapha; Rakariyatham, Nuansri

    2016-08-01

    The higher lipid productivity of Rhodotorula glutinis TISTR5159 was achieved by optimizing the pineapple pulp hydrolysis for releasing the high sugars content. The sequential simplex method operated by varied; solid-to-liquid ratio, sulfuric acid concentration, temperature, and hydrolysis time were successfully applied and the highest sugar content (83.2 g/L) evaluated at a solid-to-liquid ratio of 1:10.8, 3.2% sulfuric acid, 105 °C for 13.9 min. Moreover, the (NH4)2SO4 supplement enhanced the lipid productivity and gave the maximum yields of biomass and lipid of 15.2 g/L and 9.15 g/L (60.2%), respectively. The C16 and C18 fatty acids were found as main components included oleic acid (55.8%), palmitic acid (16.6%), linoleic acid (11.9%), and stearic acid (7.8%). These results present the possibility to convert the sugars in pineapple pulp hydrolysate to lipids. The fatty acid profile was also similar to vegetable oils. Thus, it could be used as potential feedstock for biodiesel production.

  18. ATP Release Channels

    Directory of Open Access Journals (Sweden)

    Akiyuki Taruno

    2018-03-01

    Full Text Available Adenosine triphosphate (ATP has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have been demonstrated in many cell types. Although large and negatively charged ATP molecules cannot diffuse across the lipid bilayer of the plasma membrane, conductive ATP release from the cytosol into the extracellular space is possible through ATP-permeable channels. Such channels must possess two minimum qualifications for ATP permeation: anion permeability and a large ion-conducting pore. Currently, five groups of channels are acknowledged as ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1, volume-regulated anion channels (VRACs, also known as volume-sensitive outwardly rectifying (VSOR anion channels, and maxi-anion channels (MACs. Recently, major breakthroughs have been made in the field by molecular identification of CALHM1 as the action potential-dependent ATP-release channel in taste bud cells, LRRC8s as components of VRACs, and SLCO2A1 as a core subunit of MACs. Here, the function and physiological roles of these five groups of ATP-release channels are summarized, along with a discussion on the future implications of understanding these channels.

  19. Spontaneous charged lipid transfer between lipid vesicles.

    Science.gov (United States)

    Richens, Joanna L; Tyler, Arwen I I; Barriga, Hanna M G; Bramble, Jonathan P; Law, Robert V; Brooks, Nicholas J; Seddon, John M; Ces, Oscar; O'Shea, Paul

    2017-10-03

    An assay to study the spontaneous charged lipid transfer between lipid vesicles is described. A donor/acceptor vesicle system is employed, where neutrally charged acceptor vesicles are fluorescently labelled with the electrostatic membrane probe Fluoresceinphosphatidylethanolamine (FPE). Upon addition of charged donor vesicles, transfer of negatively charged lipid occurs, resulting in a fluorescently detectable change in the membrane potential of the acceptor vesicles. Using this approach we have studied the transfer properties of a range of lipids, varying both the headgroup and the chain length. At the low vesicle concentrations chosen, the transfer follows a first-order process where lipid monomers are transferred presumably through the aqueous solution phase from donor to acceptor vesicle. The rate of transfer decreases with increasing chain length which is consistent with energy models previously reported for lipid monomer vesicle interactions. Our assay improves on existing methods allowing the study of a range of unmodified lipids, continuous monitoring of transfer and simplified experimental procedures.

  20. Lipid nanoparticle interactions and assemblies

    Science.gov (United States)

    Preiss, Matthew Ryan

    Novel liposome-nanoparticle assemblies (LNAs) provide a biologically inspired route for designing multifunctional bionanotheranostics. LNAs combine the benefits of lipids and liposomes to encapsulate, transport, and protect hydrophilic and hydrophobic therapeutics with functional nanoparticles. Functional nanoparticles endow LNAs with additional capabilities, including the ability to target diseases, triggered drug release, controlled therapeutic output, and diagnostic capabilities to produce a drug delivery system that can effectively and efficiently deliver therapeutics while reducing side effects. Not only could LNAs make existing drugs better, they could also provide an avenue to allow once promising non-approved drugs (rejected due to harmful side effects, inadequate pharmacokinetics, and poor efficacy) to be safely used through targeted and controlled delivery directly to the diseased site. LNAs have the potential to be stimuli responsive, delivering drugs on command by external (ultrasound, RF heating, etc.) or internal (pH, blood sugar, heart rate, etc.) stimuli. Individually, lipids and nanoparticles have been clinically approved for therapy, such as Doxil (a liposomal doxorubicin for cancer treatment), and diagnosis, such as Feridex (an iron oxide nanoparticle an MRI contrast enhancement agent for liver tumors). In order to engineer these multifunctional LNAs for theranostic applications, the interactions between nanoparticles and lipids must be better understood. This research sought to explore the formation, design, structures, characteristics, and functions of LNAs. To achieve this goal, different types of LNAs were formed, specifically magnetoliposomes, bilayer decorated LNAs (DLNAs), and lipid-coated magnetic nanoparticles (LMNPs). A fluorescent probe was embedded in the lipid bilayer of magnetoliposomes allowing the local temperature and membrane fluidity to be observed. When subjected to an electromagnetic field that heated the encapsulated iron

  1. The effects of particle properties on nanoparticle drug retention and release in dynamic minoxidil foams.

    Science.gov (United States)

    Zhao, Yanjun; Brown, Marc B; Jones, Stuart A

    2010-01-04

    Nanocarriers may act as useful tools to deliver therapeutic agents to the skin. However, balancing the drug-particle interactions; to ensure adequate drug loading, with the drug-vehicle interactions; to allow efficient drug release, presents a significant challenge using traditional semi-solid vehicles. The aim of this study was to determine how the physicochemical properties of nanoparticles influenced minoxidil release pre and post dose application when formulated as a simple aqueous suspension compared to dynamic hydrofluoroalkane (HFA) foams. Minoxidil loaded lipid nanoparticles (LN, 1.4 mg/ml, 50 nm) and polymeric nanoparticles with a lipid core (PN, 0.6 mg/ml, 260 nm) were produced and suspended in water to produce the aqueous suspensions. These aqueous suspensions were emulsified with HFA using pluronic surfactant to generate the foams. Approximately 60% of the minoxidil loaded into the PN and 80% of the minoxidil loaded into the LN was released into the external aqueous phase 24h after production. Drug permeation was superior from the PN, i.e. it was the particle that retained the most drugs, irrespective of the formulation method. Premature drug release, i.e. during storage, resulted in the performance of the topical formulation being dictated by the thermodynamic activity of the solubilised drug not the particle properties.

  2. Residue-specific membrane location of peptides and proteins using specifically and extensively deuterated lipids and {sup 13}C-{sup 2}H rotational-echo double-resonance solid-state NMR

    Energy Technology Data Exchange (ETDEWEB)

    Xie Li; Ghosh, Ujjayini; Schmick, Scott D.; Weliky, David P., E-mail: weliky@chemistry.msu.edu [Michigan State University, Department of Chemistry (United States)

    2013-01-15

    Residue-specific location of peptides in the hydrophobic core of membranes was examined using {sup 13}C-{sup 2}H REDOR and samples in which the lipids were selectively deuterated. The transmembrane topology of the KALP peptide was validated with this approach with substantial dephasing observed for deuteration in the bilayer center and reduced or no dephasing for deuteration closer to the headgroups. Insertion of {beta} sheet HIV and helical and {beta} sheet influenza virus fusion peptides into the hydrophobic core of the membrane was validated in samples with extensively deuterated lipids.

  3. Improved cytotoxicity of paclitaxel loaded in nanosized lipid carriers by intracellular delivery

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Jing, E-mail: joemj1005@163.com, E-mail: miaojing@zju.edu.cn [Zhejiang University, Department of Pharmacy, the First Affiliated Hospital, College of Medicine (China); Du, Yongzhong; Yuan, Hong [Zhejiang University, College of Pharmaceutical Sciences (China); Zhang, Xingguo; Li, Qian; Rao, Yuefeng [Zhejiang University, Department of Pharmacy, the First Affiliated Hospital, College of Medicine (China); Zhao, Mengdan [Zhejiang University, Women’s Hospital, College of Medicine (China); Hu, Fuqiang, E-mail: hufq@zju.edu.cn [Zhejiang University, College of Pharmaceutical Sciences (China)

    2015-01-15

    Nanosized lipid carriers (NLC) can improve the limited drug-loading (DL) capacity and drug expulsion during storage, and adjust the drug release profile of solid lipid nanoparticles (SLN). In this study, Paclitaxel (PTX)-loaded NLC were prepared by solvent diffusion method using monostearin as solid lipid and oleic acid (OA) as liquid lipid matrix. The blank NLC with different OA content (the size range was from 89.5 ± 7.4 to 160.2 ± 34.6 nm) showed smaller size than the blank SLN (the size was 272.7 ± 43.6 nm), while the PTX-loaded NLC (the size range was from 481.3 ± 29.8 to 561.7 ± 38.3 nm) showed little bigger size, higher DL capacity, and faster drug in vitro release rate comparing with SLN (the size was 437.3 ± 68.2 nm). The 50 % cellular growth inhibitions (IC{sub 50}) of PTX-loaded NLC with 0, 5, 10, and 20 wt % OA were 0.92 ± 0.06, 0.69 ± 0.04, 0.25 ± 0.02, and 0.12 ± 0.02 µg mL{sup −1}, respectively, while the IC{sub 50} of Taxol{sup TM} was 1.72 ± 0.09 µg mL{sup −1}. For analyzing cellular drug effect, cellular uptakes of fluorescent NLC and intracellular drug concentration were investigated. As the incorporation of OA into solid lipid matrix could accelerate both the cellular uptake and the PTX delivery, loaded by NLC, the cytotoxicity of PTX could be enhanced, and further enhanced by increasing OA content in NLC.

  4. Improved cytotoxicity of paclitaxel loaded in nanosized lipid carriers by intracellular delivery

    International Nuclear Information System (INIS)

    Miao, Jing; Du, Yongzhong; Yuan, Hong; Zhang, Xingguo; Li, Qian; Rao, Yuefeng; Zhao, Mengdan; Hu, Fuqiang

    2015-01-01

    Nanosized lipid carriers (NLC) can improve the limited drug-loading (DL) capacity and drug expulsion during storage, and adjust the drug release profile of solid lipid nanoparticles (SLN). In this study, Paclitaxel (PTX)-loaded NLC were prepared by solvent diffusion method using monostearin as solid lipid and oleic acid (OA) as liquid lipid matrix. The blank NLC with different OA content (the size range was from 89.5 ± 7.4 to 160.2 ± 34.6 nm) showed smaller size than the blank SLN (the size was 272.7 ± 43.6 nm), while the PTX-loaded NLC (the size range was from 481.3 ± 29.8 to 561.7 ± 38.3 nm) showed little bigger size, higher DL capacity, and faster drug in vitro release rate comparing with SLN (the size was 437.3 ± 68.2 nm). The 50 % cellular growth inhibitions (IC 50 ) of PTX-loaded NLC with 0, 5, 10, and 20 wt % OA were 0.92 ± 0.06, 0.69 ± 0.04, 0.25 ± 0.02, and 0.12 ± 0.02 µg mL −1 , respectively, while the IC 50 of Taxol TM was 1.72 ± 0.09 µg mL −1 . For analyzing cellular drug effect, cellular uptakes of fluorescent NLC and intracellular drug concentration were investigated. As the incorporation of OA into solid lipid matrix could accelerate both the cellular uptake and the PTX delivery, loaded by NLC, the cytotoxicity of PTX could be enhanced, and further enhanced by increasing OA content in NLC

  5. Nanostructured lipid carriers system: recent advances in drug delivery.

    Science.gov (United States)

    Iqbal, Md Asif; Md, Shadab; Sahni, Jasjeet Kaur; Baboota, Sanjula; Dang, Shweta; Ali, Javed

    2012-12-01

    Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.

  6. Novel Caffeic Acid Nanocarrier: Production, Characterization, and Release Modeling

    Directory of Open Access Journals (Sweden)

    Milad Fathi

    2013-01-01

    Full Text Available This paper deals with the development of novel nanocarriers using layer by layer carbohydrate coating of caffeic acid loaded solid lipid nanoparticles (SLNs to improve stability and colon delivery of the poorly water-soluble caffeic acid. Three biopolymers (chitosan, alginate, and pectin in different concentrations (0.1, 0.25, and 0.5% were electrostatically coated over the SLN surface. The size and zeta potential of produced nanocarriers were measured using photon correlation spectroscopy. Mathematical models (i.e., zero-order, first-order, Higuchi, Ritger-Peppas, reciprocal powered time, Weibull, and quadratic models were used to describe the release and kinetic modeling in gastrointestinal solution (GIS. Also, antioxidant activity of caffeic acid during the release in GIS was investigated using DPPH and reducing activity methods. The prepared treatments coated by alginate-chitosan as well as pectin-chitosan coated SLN at the concentration of 0.1% showed nanosized bead; the latter efficiently retarded the release of caffeic acid in gastric media up to 2.5 times higher than that of SLN. Zeta potential values of coated samples were found to significantly increase in comparison to SLN indicating the higher stability of produced nanocarriers. Antioxidant activity of caffeic acid after gastric release did not result in the same trend as observed for caffeic acid release from different treatments; however, in line with less caffeic acid release in the intestine solution by the effect of coating, lower antioxidant activity was determined at the end stage of the experiment.

  7. Design of lipid matrix particles for fenofibrate

    DEFF Research Database (Denmark)

    Xia, Dengning; Cui, Fude; Gan, Yong

    2014-01-01

    The effect of polymorphism of glycerol monostearate (GMS) on drug incorporation and release from lipid matrix particles (LMPs) was investigated using fenofibrate as a model drug. X-ray powder diffraction and differential scanning calorimetry were used to study the polymorphism change of GMS and t...

  8. On the interaction between fluoxetine and lipid membranes: Effect of the lipid composition

    Science.gov (United States)

    Pham, Vy T.; Nguyen, Trinh Q.; Dao, Uyen P. N.; Nguyen, Trang T.

    2018-02-01

    Molecular interaction between the antidepressant fluoxetine and lipid bilayers was investigated in order to provide insights into the drug's incorporation to lipid membranes. In particular, the effects of lipid's unsaturation degree and cholesterol content on the partitioning of fluoxetine into large unilamellar vesicles (LUVs) comprised of unsaturated 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and saturated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were evaluated using second derivative spectrophotometry and Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). It was found that fluoxetine partitioned to a greater extent into the liquid-crystalline DOPC LUVs than into the solid-gel DPPC LUVs. The lipid physical state dependence of drug partitioning was verified by increasing the temperature in which the partition coefficient of fluoxetine significantly increased upon the change of the lipid phase from solid-gel to liquid-crystalline. The incorporation of 28 mol% cholesterol into the LUVs exerted a significant influence on the drug partitioning into both DOPC and DPPC LUVs. The ATR-FTIR study revealed that fluoxetine perturbed the conformation of DOPC more strongly than that of DPPC due to the cis-double bonds in the lipid acyl chains. Fluoxetine possibly bound to the carbonyl moiety of the lipids through the hydrogen bonding formation while displaced some water molecules surrounding the PO2- regions of the lipid head groups. Cholesterol, however, could lessen the interaction between fluoxetine and the carbonyl groups of both DOPC and DPPC LUVs. These findings provided a better understanding of the role of lipid structure and cholesterol on the interaction between fluoxetine and lipid membranes, shedding more light into the drug's therapeutic action.

  9. Development, in vitro and in vivo evaluations of novel lipid drug delivery system of (P. Beauv.

    Directory of Open Access Journals (Sweden)

    Chukwuebuka Umeyor

    2016-11-01

    Full Text Available Newbouldia laevis (P. Beauv. is a tropical rainforest plant used in traditional folk medicine for the treatment of malaria, cough, joint pains, stomach ache, oedema and inflammation. The main thrust of this research work was to study the analgesic/anti-nociceptive properties of N. laevis -loaded solid lipid microdispersions. N. laevis leaves were extracted using ethanol, and the extract was formulated into solid lipid microdispersions using lipid matrix comprising a rational blend of Precirol ® ATO 5 and Softisan ® 154. Characterization of the solid lipid microdispersions include determination of morphology, particle size, pH, thermal property, encapsulation efficiency percentage and analgesic/anti-nociceptive property. The results obtained showed that the particles were spherical with sizes ranging from 40 µm to 125 µm. The solid lipid microdispersions maintained a stable pH within the acidic region of 5–6 with insignificant variations ( p > 0.05 over a period of 90 days. Thermal analysis showed that N. laevis was entrapped in the lipid matrix used for the formulations. Solid lipid microdispersions recorded a maximum encapsulation efficiency up to 88.1%. N. laevis -loaded solid lipid microdispersions also produced good analgesic/anti-nociceptive property comparable with the standard diclofenac potassium. N. laevis -loaded solid lipid microdispersions showed good analgesic/anti-nociceptive effect and could be used in the treatment and management of pain.

  10. Stepwise encapsulation and controlled two-stage release system for cis-Diamminediiodoplatinum

    Directory of Open Access Journals (Sweden)

    Chen Y

    2014-06-01