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Polymeric systems made of poly(lactic acid) or poly(lactic-co-glycolic acid) are widely used for long-term delivery of small and large molecules. The advantages of poly(lactic acid)/poly(lactic-co-glycolic acid) systems include biodegradability, safety and a long history of use in US FDA-approved products. However, as drugs delivered by the polymeric systems and their applications become more diverse, the significance of microenvironment change of degrading systems on long-term drug stability and release kinetics has gained renewed attention. In this review, we discuss various issues experienced with acidifying microenvironment of biodegradable polymer systems and approaches to overcome the detrimental effects of polymer degradation on drug stability and release control.

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