A comprehensive study of the influence of particle size and pH on the degradation of poly(lactide-co-glycolide)-based microspheres

IGNACIO M. HELBLING; CARLOS BUSATTO; JUAN C. D. IBARRA; DIANA ESTENOZ; JULIO A. LUNA

Beijing

Simposio; 5th Annual World Symposium of Drug Delivery System; 2015

Biodegradable microspheres have been studied extensively as deliveryvehicles for drugs. Drug delivery from biodegradable microspheres provideseveral advantages compared to conventional pharmaceutical dosage forms, suchas: (i) the possibility to accurately control the drug release rates overextended periods of time, (ii) easy administration and (iii) completebiodegradation. Among the various biodegradable polymers used to preparemicrospheres, poly(lactic-co-glycolic acid) copolymer(PLGA) is one of the most used because of its biocompatibility, long clinical experience,controllable degradation characteristics and possibilities for sustained drugdelivery. In the present contribution, PLGA-based microspheres were prepared bythe oil-in-water emulsion solvent evaporation technique. Degradation studiesfrom different particle sizes were carried out in aqueous environment at 37ºC. Buffered and un-bufferedsolutions were used to analyze the effect of pH variation on degradationbehaviour. Size exclusion chromatography (SEC), scanning electron microscopy(SEM), nuclear magnetic resonance (NMR) and differential scanning calorimetry(DSC) techniques and gravimetric and pH measurements were used to evaluate thedegradation and microsphere morphological changes. Results showed a two-phasedegradation for all systems: A first stage of around 14 days in wheredegradation rates were slower (kd =5-20 10-3 days-1) followed by a second stage in wheredegradation becomes faster (kd = 20-80 10-3 days-1).All microspheres suffered bulk degradation. Degradation was faster in un-buffered than in buffered solutions. Also, largermicrospheres degrades faster than smaller particles. These results could be dueto the autocatalytic effect generated by acidic environment inside largermicrospheres. A drop in the microenvironmental pH accelerate PLGA degradationbecause the ester bond cleavage is catalyzed by protons. RMN analysis showedthat cleavage occurs in both lactide and glicolide residues with same frequency.No preference cleavage was observed. Drug delivery from PLGA-based microspherescould be controlled by polymer degradation. As larger microspheres degradesfaster, it can be expected that release rates be higher in that system than insmaller particles. In conclusion, larger PLGA microspheres could be used torapid delivery of drugs while smaller microspheres could be used to a moreextended release.