Abstract
Poly(lactic-co-glycolic acid) (PLGA) is the most widely used biomaterial for microencapsulation and prolonged delivery of therapeutic drugs, proteins and antigens. PLGA has excellent biodegradability and biocompatibility and is generally recognized as safe by international regulatory agencies including the United States Food and Drug Administration and the European Medicines Agency. The physicochemical properties of PLGA may be varied systematically by changing the ratio of lactic acid to glycolic acid. This in turn alters the release rate of microencapsulated therapeutic molecules from PLGA microparticle formulations. The obstacles hindering more widespread use of PLGA for producing sustained-release formulations for clinical use include low drug loading, particularly of hydrophilic small molecules, high initial burst release and/or poor formulation stability. In this review, we address strategies aimed at overcoming these challenges. These include use of low-temperature double-emulsion methods to increase drug-loading by producing PLGA particles with a small volume for the inner water phase and a suitable pH of the external phase. Newer strategies for producing PLGA particles with high drug loading and the desired sustained-release profiles include fabrication of multi-layered microparticles, nanoparticles-in-microparticles, use of hydrogel templates, as well as coaxial electrospray, microfluidics, and supercritical carbon dioxide methods. Another recent strategy with promise for producing particles with well-controlled and reproducible sustained-release profiles involves complexation of PLGA with additives such as polyethylene glycol, poly(ortho esters), chitosan, alginate, caffeic acid, hyaluronic acid, and silicon dioxide.
Highlights
Drug delivery systems with high efficiency and tuneable release characteristics continue to be sought. This is despite recent advances in the field of nanobiotechnology that have produced a range of new materials for improving control over drug delivery rates (Hillery et al, 2005)
Poly(lactic-co-glycolic acid) (PLGA) is generally recognized as safe by international regulatory agencies such as the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for use in pharmaceutical products administered to humans via conventional oral and parenteral routes (YunSeok et al, 2010) as well as suspension formulations for implantation without surgical procedures (Freiberg and Zhu, 2004)
Based upon the diversity of encapsulated drug release profiles produced by PLGA microspheres of varying sizes to date (Table 1), release rates do not necessarily conform to predicted behavior and it is only possible to quantitatively predict the effect of microparticle size on drug release kinetics for certain well-defined formulations (Siepmann et al, 2004)
Summary
Drug delivery systems with high efficiency and tuneable release characteristics continue to be sought. For PLGA microparticles, release of the encapsulated drug occurs via diffusion and/or homogeneous bulk erosion of the biopolymer (Siegel et al, 2006; Kamaly et al, 2016) with the diffusion rate dependent upon drug diffusivity and partition coefficient (Hillery et al, 2005) These parameters are influenced by the physicochemical properties of the drug, such as molecular size, hydrophilicity, and charge (Hillery et al, 2005). Based upon the diversity of encapsulated drug release profiles produced by PLGA microspheres of varying sizes to date (Table 1), release rates do not necessarily conform to predicted behavior and it is only possible to quantitatively predict the effect of microparticle size on drug release kinetics for certain well-defined formulations (Siepmann et al, 2004). (1) Particle size Drug loading and release rates from PLGA particles do not necessarily conform to predicted behavior as the effect of microparticle size on drug release kinetics quantitatively can only be predicted for certain well-defined formulations
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
