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K.G. Janoria, S. Duvvuri, A.K. Mitra; Poly (Lactide–Co–Glycolide) Microspheres for the Controlled Delivery of Ganciclovir to the Posterior Segment of the Eye: In vitro Release and Intravitreal Pharmacokinetics . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4497.
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Objectives of the current studies are: (a) to study the effect of PLGA polymer blending on GCV release (b) to prepare and characterize a formulation containing GCV loaded microspheres dispersed in thermogelling polymer that releases GCV continuously for 1 month (c) to study the vitreal GCV pharmacokinetics following intravitreal administration of the formulation.
PLGA 6535 (lactide: glycolide:: 65:35; Mw = 45,000 da) and Resomer 502H (lactide:glycolide::50:50; Mw = 8000 da) were used for preparation of GCV loaded microspheres. Thermogelling polymer (PLGA–PEG–PLGA) was synthesized and characterized. In vitro release studies were performed and both polymer blending (PLGA 6535: Resomer 502H::3:1) and microsphere blending (Resomer 502H and PLGA6535:Resomer 502H blend microspheres) strategies were investigated for their potential to release GCV continuously for 1 month. The formulation is then administered to rabbits with microdialysis probes implanted in the vitreous and GCV levels monitored for 14 days.
A series of sigmoidal equations were developed to exactly characterize GCV release from PLGA microspheres. Particle sizes ranged with in 200 – 250 µm. Entrapment studies revealed that micorpsheres prepared from polymer blends entrap greater amounts than single polymers. In vitro release studies show that PLGA 6535 releases GCV over 70 days, where as Resomer 502H over 10 days. Moreover, microspheres where polymer blends were employed; durations of drug release were intermediate. A formulation was prepared by using a blend of GCV loaded microspheres of PLGA6535:502H:: 3:1 and Resomer 502H dispersed in PLGA–PEG–PLGA gel. In vitro release studies demonstrate a dual release phase from the formulation with an average release rate of 4.85 µg/day. Intravitreal administration of this formulation into rabbit vitreous maintained GCV levels at 1 µg/ml in the vitreous for 14 days.
PLGA polymeric microspheres can be designed for desired duration and release rates. Moreover, both polymer and microsphere blends can be used for this purpose. When administered along with thermogelling polymers, these microspheres remain entrapped in the gel matrix and do not migrate in the vitreous. Vitreal administration of the formulation did not cause any toxic effects in the retina.
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