Mechanistic study of hydrolytic erosion and drug release behaviour of PLGA nanoparticles: Influence of chitosan

The hydrolytic erosion of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (PLGA-NPs) was investigated in vitro. The changes in physical properties of the nanoparticles with time were evaluated by ultra high-pressure liquid chromatographic (UHPLC) analysis, particle size analysis and scanning electron microscopy (SEM). Mass reduction data demonstrated a triphasic erosion pattern for PLGA-NPs with nearly no mass loss (3.0%) up to a week, followed by a rapid mass loss (weeks 1-3, 61.4%), and further followed by slow mass loss (weeks 3-5, 19.8%). SEM revealed microcavitation on the surface of nanoparticles, which tended to increase with the erosion time and eventually particle fragmentation was evident at 5 weeks. A significant increase in particle size was observed at 4 weeks which can be attributed to particle aggregation, however, at about 5 weeks, the particle size decreased significantly owing to particle fragmentation. The hydrolytic erosion of PLGA-NPs was found to be specifically proton catalyzed. The release profile of the model drug, moxifloxacin, from PLGA-NPs was closely related to nanoparticle erosion except for the initial burst release which was based on diffusion. The presence of chitosan in the PLGA-NPs accelerated the rate of erosion of the nanoparticles and reduced the burst release of the drug. An understanding of the erosion mechanism and alteration in erosion by chitosan could give desirable and more uniform drug release kinetics from PLGA-NPs.