Guémené-sur-Scorff, pays des Pourleths... Illustrations : Joë Le Fur / Paul Le Bourlais

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Supercritical fluid impregnation of a biocompatible polymer for ophthalmic drug delivery

Supercritical fluid impregnation was tested to prepare a new ophthalmic drug delivery device. Poly(methylmethacrylate-co-ethylhexylacrylate-co-ethyleneglycoldimethacrylate), P(MMA-EHA-EGDMA) has been proposed by Mariz [M. Mariz, Preparação de uma lente intra-ocular dotada de um sistema de libertação controlada de fármaco, Master Thesis, Universidade de Coimbra, 1999] as a promising matrix to be used for intraocular delivery of anti-inflammatory drugs used in eye surgery. This matrix was successfully impregnated with flurbiprofen, a non-steroidal anti-inflammatory agent.http://www.sciencedirect.com/science/article/B6VMF-4N02J5M-1/1/ee8d7c5effb50ccf2b99656a67b77da

Ocular injectable formulation assessment for oxidized dextran-based hydrogels

Initiator-free injectable hydrogels are very interesting for drug and/or cell delivery applications, since they can be administered in a minimally invasive way, and avoid the use of potentially harmful chemical initiators. In the current work, oxidized dextran crosslinked with adipic acid dihydrazide hydrogels were further characterized and tuned to produce formulations, with the aim of producing an injectable formulation for the possible treatment of posterior eye diseases. The gelation rate and the hydrogel dissolution profile were shown to be dependent on the balance between the degree of dextran oxidation, and the concentration of both components. For the in vitro studies, rabbit corneal endothelial cells were seeded on the hydrogels to assess cytotoxicity. Hydrogels prepared with low oxidized dextrans were able to promote cell adhesion and proliferation to confluence in just 24 h, while more highly oxidized samples promoted cell adhesion and proliferation, but without achieving confluence. Cell viability studies were performed using MTS assays to verify the non-cytotoxicity of hydrogels and their degradation byproducts, rendering these formulations attractive for further in vivo studies.Instituto de Investigação Interdisciplinar (financial support of JM – III/BIO/20/2005); Portuguese Foundation for Science and Technology (in the form of fellowship to IJC - SFRH/BPD/19776/2004

Supercritical solvent impregnation of poly(ɛ-caprolactone)/poly(oxyethylene-b-oxypropylene-b-oxyethylene) and poly(ɛ-caprolactone)/poly(ethylene-vinyl acetate) blends for controlled release applications

Poly(ɛ-caprolactone) blends were successfully impregnated with timolol maleate, an anti-glaucoma drug, using a supercritical solvent impregnation (SSI) technique. Supercritical fluid impregnation efficiency results suggested that the best impregnating conditions were obtained when a cosolvent was used and when specific drug–polymer interactions occurred as a consequence of different chemical structures due to polymer blending. Pressure can be either a favourable factor, when there is enough drug affinity for the polymers, or an unfavourable factor when weaker bonding is involved. In order to determine the relative hydrophilicity/hydrophobicity of the blends, contact angle analysis was performed, while crystallinity determination was also useful to understand the obtained release profiles. Drug loading, heterogeneous/homogeneous dispersion of drug inside the matrix, hydrophilicity, crystallinity, all seem to influence the obtained drug release rates. The “in vitro” release results suggested that a sustained drug release rate can be obtained by changing the SSI operational conditions and by modulating the composition of blends, as a mean to control crystallinity, hydrophilicity and drug affinity for the polymer matrix. After a first day burst release, all samples showed a sustained release profile (1.2–4 μg/(ml day), corresponding to a mass of 3–10 μg/day) which is between the therapeutic and toxic levels of timolol maleate, during a period of 1 month. These drug-loaded polymeric matrices can be a feasible alternative treatment modality for the conventional repeated daily administration of eye drops

Self-​assembling colloidal system for the ocular administration of cyclosporine A

PURPOSE: In this study, we developed a self-assembling micellar system to deliver cyclosporine A (CsA) in an aqueous solution to the cornea. METHODS: Two nonionic surfactants of the poly(ethylene glycol)-fatty alcohol ether type (Sympatens AS and Sympatens ACS) were characterized in terms of micelle size, shape, and charge, and their encapsulation efficiency for CsA. In an in situ single dose bioavailability study, the corneal CsA levels were determined in an enucleated porcine eye model. A commercial formulation and a 2% CsA olive oil solution served as references. RESULTS: Both surfactants formed spherical micelles with a size of 9 to 12 nm in water. A concentration as low as 0.3% (wt/vol) Sympatens AS was sufficient to entrap therapeutic levels of at least 0.1% (wt/vol) CsA. In the porcine in situ model, exceptionally high drug levels in the cornea were obtained for the micellar CsA solution (1557 ± 407 ngCsA/gcornea). They were significantly higher than those of Restasis (545 ± 137 ngCsA/gcornea) or the olive oil solution (452 ± 142 ngCsA/gcornea). CONCLUSIONS: In conclusion, we have shown a promising simple and efficient approach for the application of CsA in an aqueous solution to the cornea to treat inflammatory corneal diseases