Phenomenology of the Initial Burst Release of Drugs from PLGA Microparticles

Poly­(lactic-co-glycolic acid) (PLGA) is the most prevalent polymer drug delivery vehicle in use today. There are about 20 commercialized drug products in which PLGA is used as an excipient. In more than half of these formulations, PLGA is used in the form of microparticles (with sizes in the range between 60 nm and 100 μm). The primary role of PLGA is to control the kinetics of drug release toward achieving sustained release of the drug. Unfortunately, most drug-loaded PLGA microparticles exhibit a common drawback: an initial uncontrolled burst of the drug. After 30 years of utilization of PLGA in controlled drug delivery systems, this initial burst drug release still remains an unresolved challenge. In this Review, we present a summary of the proposed mechanisms responsible for this phenomenon and the known factors affecting the burst release process. Also, we discuss examples of recent efforts made to reduce the initial burst release of the drug from PLGA particles.