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J Control Release. 2005 Nov 28;108(2-3):282-93. Epub 2005 Oct 17.

Development of a novel formulation containing poly(d,l-lactide-co-glycolide) microspheres dispersed in PLGA-PEG-PLGA gel for sustained delivery of ganciclovir.

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  • 1Department of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 5005, Rockhill road, Kansas City, MO 64110, USA.


The purpose of this work is to develop empirical equations for describing the in vitro ganciclovir (GCV) release from PLGA microspheres and also to develop and characterize a formulation containing GCV loaded PLGA microspheres dispersed in thermogelling PLGA-PEG-PLGA polymer gel. Effect of polymer chain length and polymer blending on GCV entrapment and release from PLGA microspheres is also examined. PLGA microspheres of GCV were prepared from two polymers PLGA 6535 (d,l-lactide:glycolideColon, two colons65:35, Mw=45,000-75,000 Da) and Resomer RG 502H (d,l-lactide:glycolideColon, two colons50:50, Mw=8000 Da) and a 3:1 mixture. PLGA-PEG-PLGA polymer was synthesized and characterized. In vitro GCV release studies were conducted with microspheres and microspheres dispersed in 23% w/v PLGA-PEG-PLGA solution. Polymer blended microspheres entrap more GCV (72.67+/-2.49%) than both PLGA 6535 (51.37+/-2.7%) and Resomer RG 502H (47.13+/-1.13%) microspheres. In vitro drug release data was fit to sigmoid equations and release parameters were estimated by nonlinear regression analysis. These equations effectively describe three different phases in GCV release from PLGA microspheres, initial diffusion, matrix hydration and degradation. The amount of drug release during the initial phase decreased for the blend microspheres indicating efficient packing between the PLGA 6535 and Resomer RG 502H in the microsphere matrix. Moreover, upon dispersion into the polymer gel, the rate of drug release during initial diffusion phases slowed relative to microspheres alone. In conclusion, this study reports the development of PLGA microspheres with high payloads and their PLGA-PEG-PLGA gel based formulations. Drug release equations have been developed that effectively describe the triphasic GCV release.

[PubMed - indexed for MEDLINE]
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