Analysis of particle size, polydispersity and polymer degradation on progesterone delivery from PLGA-based microparticles: Experimental and mathematical modelling

JUAN PESOA; DIANA ESTENOZ; IGNACIO HELBLING; CARLOS BUSATTO; JULIO LUNA

Montreal

Simposio; 18th International Biotechnology Symposium and Exhibition; 2018

Poly(lactic-co-glycolic acid) (PLGA) has been widely studied as biomaterial for drug delivery applications [1]. Progesterone is a lipophilic steroid hormone with low molecular weight. Several progesterone delivery systems based on biodegradable and non-biodegradable polymeric matrices has been used for estrous regulation in production animals [2]. Biodegradable microparticles are of special interest because they present several advantages, such as easy preparation and administration, do not require surgical intervention to remove the material and it is possible to control the release and degradation rates based on the physicochemical properties of the polymer. In this study, PLGA microparticles for progesterone delivery were prepared by the solvent extraction/evaporation and microfluidic techniques. Microparticles were characterized by size distribution, morphology, encapsulation efficiency and thermal properties. The effect of particle size, polydispersity and polymer degradation on the in vitro release of progesterone was studied. Biphasic and triphasic release profiles were observed for smaller and larger microparticles, respectively. This behavior is related to the complete drug release in a few days for smaller microparticles, during which polymer degradation effects are still negligible. Microparticles prepared by microfluidics showed a release profile with high reproducibility compared to microparticles prepared by the conventional technique. A mathematical model for the prediction of progesterone release from PLGA microspheres was developed. Our previous model for the heterogeneous hydrolytic degradation of PLGA microspheres [3] was extended in order to incorporate the drug dissolution and diffusion in the polymeric matrix. The model was adjusted and validated with the experimental data. Simulation results are in very good agreement with experimental results [4].