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Research Project
INTRAOCULAR CONTROLLED RELEASE SYSTEM FOR OPTHALMOLOGIC APPLICATIONS
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A poly(ε-caprolactone) device for sustained release of an anti-glaucoma drug
Publication . Natu, Mădălina; Gaspar, Manuel; Ribeiro, Carlos; Correia, Ilídio Joaquim Sobreira; Silva, Daniela; Sousa, Hermínio C. de; Gil, Maria
Implantable dorzolamide-loaded discs were prepared by blending poly(ε-caprolactone), PCL, with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), Lu. By blending, crystallinity, water uptake and mass loss were modified relative to the pure polymers. Burst was diminished by coating the discs with a PCL shell. All samples presented burst release except PCL-coated samples that showed controlled release during 18 days. For PCL-coated samples, barrier control of diffusion coupled with partition control from the core slowed down the release, while for 50/50 Lu/PCL-coated samples, the enhancement in the porosity of the core diminished partition control of drug release. Nonlinear regression analysis suggested that a degradation model fully describes the release curve considering a triphasic release mechanism: the instantaneous diffusion (burst), diffusion and polymer degradation stages. The MTT test indicated that the materials are not cytotoxic for corneal endothelial cells. A good in vitro–in vivo correlation was obtained, with similar amounts of drug released in vitro and in vivo. The discs decreased intraocular pressure (IOP) in normotensive rabbit eyes by 13.0% during 10 days for PCL-coated and by 13.0% during 4 days for 50/50 Lu/PCL-coated samples. The percentages of IOP decrease are similar to those obtained by dorzolamide eyedrop instillation (11.0%).
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Fundação para a Ciência e a Tecnologia
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POSI
Funding Award Number
SFRH/BD/30198/2006