Journal Title
Title of Journal: Drug Deliv and Transl Res
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Abbravation: Drug Delivery and Translational Research
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Authors: Namdev B Shelke Rajendra Kadam Puneet Tyagi Vidhya R Rao Uday B Kompella
Publish Date: 2010/12/22
Volume: 1, Issue: 1, Pages: 76-90
Abstract
While poorly soluble drugs such as corticosteroids sustain drug delivery in the vitreous humor by virtue of slow dissolution macromolecules such as antibodies and their fragments sustain their levels due to their slow clearance However currently there are no approaches to sustain the delivery of well watersoluble small molecule drugs in the vitreous In this study we optimized a polyllactide PLA microparticle formulation for sustained intravitreal delivery of TG0054 a well watersoluble antiangiogenic drug that is of potential value in treating choroid neovascularization After determining the influence of process parameters on particle size and drug loading spherical microparticles syringeable through a 27G needle with a mean diameter of 76 μm 10 w/w TG0054 loading sustained in vitro drug release for at least 6 months and low residual organic solvent content ~ 1 ppb/mg were prepared Microparticles as well as drug solution were assessed for their in vivo drug delivery over 3 months following intravitreal injection in New Zealand white rabbits Drug levels in the microparticle dosed eyes at 3 months were 437 ± 162 243 ± 426 and 628 ± 226 μg/g vitreous retina and choroid–retinal pigment epithelium RPE respectively and similar to levels at 1 month Intravitreal injection of plain drug solution resulted in significantly lower amounts of drug in the dosed eye with the levels being 08 ± 05 27 ± 28 and 49 ± 42 μg/g in vitreous retina and choroid–RPE respectively at 1 month with no detectable drug at 3 months Although surface degradation was evident microparticles maintained their spherical structure during the 6month in vitro study and the 3month in vivo study with the vitreal particle retention at 1 and 3 months being 60 and 27 respectively Thus PLA microparticles capable of sustaining retinal and choroidal delivery of TG0054 for 3 to 6 months were developed
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