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Jens Thies, Mirian Gillissen, Lukasz Koroniak, George Mihov, Martina Kropp, Gabriele Thumann; Slow-release latanoprost delivery by DSM’s injectable PEA microfibers. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5256.
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Since compliance for the treatments for ocular hypertension and glaucoma with topical drugs is poor, sustained dosage forms are critical for more advanced treatment of these diseases. Subconjunctival implantation of (polyester)amide (PEA) microfibers containing drugs currently used to treat ocular hypertension and glaucoma have the potential to safely degrade in the tissue while providing long term delivery of the drug and associated reduction of intraocular pressure. Here we have investigated the release of latanoprost, a prostaglandin analogue used to treat glaucoma, by PEA microfibers in vitro as well as PEA microfiber behavior after subconjunctival and intravitreal implantation.
PEA fibers were prepared by thermal and solvent based processing to construct fibers of 200 µm in diameter and 4-5 mm in length containing 0, 7 or 15 wt% latanoprost. In-vitro release was analyzed by incubation of latanoprost-loaded PEA fibers at 37°C in PBS. Latanoprost release was quantified by HPLC analysis. Ocular biocompatibility was assessed by implantation of PEA fibers subconjunctivally and intravitreally in rabbits.
Latanoprost-loaded microfibers were engineered to release the drug from day 7 to day 35 at a rate of 0.01 µg to 0.5µg latanoprost per day. Previous studies indicated continued release up to six months in-vitro. Biocompatibility of PEA microfibers subconjunctivally and intravitreally was excellent during the 6-month follow up as evidenced by the absence of inflammatory reactions or alteration after complete clinical examination including ERG.
PEA microfibers can be engineered to release drugs over long periods of time. Here we have shown that in vitro PEA microfibers release latanoprost over a period of 35 days and that subconjunctival implantation of PEA microfibers is safe and, therefore, could be useful for the delivery of drugs to treat hypertension and glaucoma.
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