Effect of non-cross-linked calcium on characteristics, swelling, drug release and mucoadhesion of calcium alginate beads

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Retinal cell regeneration using tissue engineered polymeric scaffolds

Degenerative retinal diseases, such as age-related macular degeneration (AMD), can lead to permanent sight loss. Although intravitreal anti-vascular endothelial growth factor (VEGF) and steroid injections are effective for the management of early stages of wet and/or neovascular AMD (nAMD), no proven treatments currently exist for dry AMD or for the advanced geographic atrophy of the retina that follows. Tissue engineering (TE) has recently emerged as a promising alternative to repair retinal damaged and restore its functions. Here, we review recent advances in TE, with a particular emphasis on retinal regeneration. We provide an overview of retinal diseases, followed by a comprehensive review of TE techniques, cells, and polymers used in the fabrication of scaffolds for retinal cell regenerations, in particular the retinal pigment epithelium (RPE). - 2019Scopu

Sunscreens containing cyclodextrin inclusion complexes for enhanced efficiency : a strategy for skin cancer prevention

Unprotected exposure of skin to solar ultraviolet radiation (UVR) may damage the DNA of skin cells and can lead to skin cancer. Sunscreens are topical formulations used to protect skin against UVR. The active ingredients of sunscreens are UV filters that absorb, scatter, and/or reflect UVR. Preventing the formation of free radicals and repairing DNA damages, natural antioxidants are also added to sunscreens as a second fold of protection against UVR. Antioxidants can help stabilise these formulations during the manufacturing process and upon application on skin. However, UV filters and antioxidants are both susceptible to degradation upon exposure to sunlight and oxygen. Additionally, due to their poor water solubility, natural antioxidants are challenging to formulate and exhibit limited penetration and bioavailability in the site of action (i.e., deeper skin layers). Cyclodextrins (CDs) are cyclic oligosaccharides that are capable of forming inclusion complexes with poorly soluble drugs, such as antioxidants. In this review, we discuss the use of CDs inclusion complexes to enhance the aqueous solubility of antioxidants and chemical UV filters and provide a protective shield against degradative factors. The role of CDs in providing a controlled drug release profile from sunscreens is also discussed. Finally, incorporating CDs inclusion complexes into sunscreens has the potential to increase their efficiency and hence improve their skin cancer prevention

Potential use of the Maillard reaction for pharmaceutical applications : gastric and intestinal controlled release alginate-albumin beads

In this study, bovine serum albumin (BSA) and alginate (ALG) conjugates were synthesized by the Maillard reaction in order to evaluate their potential to develop controlled release drug delivery systems. The progress of the Maillard reaction was evidenced using ultraviolet (UV) absorbance, determination of BSA remaining free amino groups, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). BSA-ALG conjugates possessed enhanced and tunable viscosity, foamability and foam stability. Foam generated from BSA-ALG conjugate solution was used to prepare floating gastroretentive calcium ALG beads. Unlike traditional ALG beads, BSA-ALG foam beads were able to float and sustain the ciprofloxacin (CIP) release in gastric medium. Interestingly, intestinal beads made of ALG, BSA-ALG physical mixture and BSA-ALG conjugate resulted in different release rates and orders of indomethacin (IND) in simulated intestinal fluids; while beads based on a physical mixture of BSA-ALG resulted in a first order sustained release profile, both systems based on ALG and BSA-ALG conjugate displayed zero order sustained release profiles with IND being released at a slower rate from the conjugate bead

Cyclodextrin Diethyldithiocarbamate Copper II Inclusion Complexes: A Promising Chemotherapeutic Delivery System against Chemoresistant Triple Negative Breast Cancer Cell Lines

Diethyldithiocarbamate Copper II (DDC-Cu) has shown potent anticancer activity against a wide range of cancer cells, but further investigations are hindered by its practical insolubility in water. In this study, inclusion complexes of DDC-Cu with hydroxypropyl beta-cyclodextrin (HP) or sulfobutyl ether beta-cyclodextrin (SBE) were prepared and investigated as an approach to enhance the apparent solubility of DDC-Cu. Formulations were prepared by simple mixing of DDC-Cu with both cyclodextrin (CDs) at room temperature. Phase solubility assessments of the resulting solutions were performed. DDC-Cu CD solutions were freeze-dried for further characterisations by DSC, thermogravimetric analysis (TGA) and FT-IR. Stability and cytotoxicity studies were also performed to investigate the maintenance of DDC-Cu anticancer activity. The phase solubility profile deviated positively from the linearity (Ap type) showing significant solubility enhancement of the DDC-Cu in both CD solutions (approximately 4 mg/mL at 20% w/w CD solutions). The DSC and TGA analysis confirmed the solid solution status of DDC-Cu in CD. The resulting solutions of DDC-Cu were stable for 28 days and conveyed the anticancer activity of DDC-Cu on chemoresistant triple negative breast cancer cell lines, with IC50 values less than 200 nM. Overall, cyclodextrin DDC-Cu complexes offer a great potential for anticancer applications, as evidenced by their very positive effects against chemoresistant triple negative breast cancer cells

Billes de pectine encapsulant du charbon actif pour l'élimination de la ciprofloxacine résiduelle dans le tube digestif

Les antibiotiques résiduels dans le tube digestif, suite à une antibiothérapie orale ou parentérale, sont à l'origine de nombreux effets délétères sur la flore intestinale aboutissant à la sélection de nouvelles résistances aux antibiotiques. L'objectif de cette thèse est d'élaborer un système galénique à base des billes de pectine pour l'administration orale du charbon actif qui permettrait, après une libération contrôlée, l'inactivation intra-intestinale des résidus actifs des antibiotiques. Au cours des travaux réalisés pendant cette thèse, des libérations contrôlées du charbon actif dans les milieux intestinal et colique simulés ont été obtenues en variant la quantité du zinc résiduel dans les billes. La co-administration des billes conçues pour le ciblage intestinal avec la ciprofloxacine à des rats a entrainé une diminution significative d environ 70% de la concentration fécale de ciprofloxacine active sans affecter sa pharmacocinétique. Ce travail pourrait offrir une nouvelle stratégie pour protéger la flore intestinale contre les effets délétères associés à l antibiothérapie et lutter contre la sélection et la dissimilation de nouvelles résistances aux antibiotiques.Residual antibiotics reaching the colon have many deleterious effects on the colonic microbiota including the selection of new antibiotic resistances. The goal of this thesis is to develop a pharmaceutical system based on pectin beads for the oral administration of activated carbon for the intra-intestinal inactivation of residual ciprofloxacin. The work performed during this thesis allowed the preparation of intestine and colon-targeted beads by adjusting the concentration of residual zinc in beads. The co-administration of intestine-targeted beads with ciprofloxacin in the rat model led to a significant decrease of the residual fecal free ciprofloxacin without affecting its pharmacokinetics. This work may provide a new strategy to protect the gut against the deleterious effects associated with antibiotherapy and may prevent the emergence of ciprofloxacin resistance in the gastrointestinalCHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

A Novel Multilayer Natural Coating for Fed-State Gastric Protection

Several nutraceutical products require gastric protection against the hostile environment in the stomach. Currently marketed synthetic and semi-synthetic coatings suffer from major shortcomings such as poor gastric protection, slow-release response to pH change, and the use of artificial ingredients. The challenge of coating natural products is further exacerbated by the relatively high gastric pH in the fed state. In this work, a novel natural enteric coating is presented as a breakthrough alternative to current solutions. Two coating systems were devised: (i) a triple-layer coating that comprises a wax layer embedded between two alginate-based coatings, and (ii) a double-layer coating, where an overcoat of organic acids (fumaric or citric acid) is applied to an alginate-based coating. The multi-layer architecture did not impact the pH-responsive nature of the coating even when more biologically relevant Krebs bicarbonate buffer of lower buffer capacity was used. Interestingly, the gastric protection barrier of organic acid-based coating remained resistant at elevated gastric pH 2, 3, or 4 for 2 h. This is the first report of using an alginate-based coating to provide gastric protection against fed-state stomach conditions (pH 2−4). Being biodegradable, naturally occurring, and with no limit on daily intake, the reported novel coating provides a superior platform to current coating solutions for pharmaceutical and nutraceutical products

Solid dispersions of gefitinib prepared by spray drying with improved mucoadhesive and drug dissolution properties

Gefitinib is a tyrosine kinase inhibitor that is intended for oral administration yet suffers poor bioavailability along with undesirable side effects. To enhance its solubility and allow colon targeting, gefitinib (ZD) and blends of different ratios of polymers (ternary dispersion) were prepared in organic solution, and solid dispersions were generated employing the spray drying (SD) technique. The methylmethacrylate polymer Eudragit S 100 was incorporated for colon targeting; polyvinylpyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC) were utilised to improve the solubility of ZD. SEM, DSC, XRPD, FT-IR, dissolution and cytotoxicity studies were undertaken to characterise and evaluate the developed formulations. SEM images revealed that the rod-shaped crystals of ZD were transformed into collapsed spheres with smaller particle size in the spray-dried particles. DSC, FTIR and XRPD studies showed that ZD loaded in the spray-dried dispersions was amorphous. ZD dissolution and release studies revealed that while a significant (P < 0.05) increase in the ZD dissolution and release was observed from HPMC-based solid dispersion at pH 7.2 (up to 95% in 15 h), practically no drug was released at pH 1.2 and pH 6.5. Furthermore, the HPMC-based solid dispersions displayed enhanced mucoadhesive properties compared with PVP-based ones. Interestingly, cell viability studies using the neutral red assay showed that PVP and HPMC-based solid dispersions had no additional inhibitory effect on Caco-2 cell line compared to the pure drug

In Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugates

The present study compares the use of high generation G3 and low generation G0 Polyamidoamine (PAMAM) dendrimers as drug carriers of naproxen (NAP), a poorly water soluble drug. Naproxen was conjugated to G3 in different ratios and to G0 in a 1:1 ratio via a diethylene glycol linker. A lauroyl chain (L), a lipophilic permeability enhancer, was attached to G3 and G0 prodrugs. The G3 and G0 conjugates were more hydrophilic than naproxen as evaluated by the measurement of partitioning between 1-octanol and a phosphate buffer at pH 7.4 and pH 1.2. The unmodified surface PAMAM-NAP conjugates showed significant solubility enhancements of NAP at pH 1.2; however, with the number of NAP conjugated to G3, this was limited to 10 molecules. The lactate dehydrogenase (LDH) assay indicated that the G3 dendrimer conjugates had a concentration dependent toxicity towards Caco-2 cells. Attaching naproxen to the surface of the dendrimer increased the IC50 of the resulting prodrugs towards Caco-2 cells. The lauroyl G3 conjugates showed the highest toxicity amongst the PAMAM dendrimer conjugates investigated and were significantly more toxic than the lauroyl-G0-naproxen conjugates. The permeability of naproxen across monolayers of Caco-2 cells was significantly increased by its conjugation to either G3 or G0 PAMAM dendrimers. Lauroyl-G0 conjugates displayed considerably lower cytotoxicity than G3 conjugates and may be preferable for use as a drug carrier for low soluble drugs such as naproxen