Spherical and spheroidal biodegradable particles from poly(D,L-lactide-co-glycolide): preparation and properties

In the literature there are numerous reports on preparation, properties and application of biodegradable particles in targeted drug delivery systems to various organs in the human body. However, information on properties and degradation of these systems is still very scarce. The aim of the study was preparation and characterization of spherical and spheroidal particles composed of poly(D,L-lactide-co-glycolide, PGLA) (Resomer® RG504H). Furthermore, our investigations led to finding relations between shape of particles and degradation mechanism determined in vitro. The spherical particles with Dn=3.2 μm and dispersity factor equal 1.3 were obtained via classical nanoprecipitation method using poly(vinyl alcohol) (PVA) as emulsifier in water. The PGLA microspheres embedded in PVA film underwent deformation into prolate spheroids in Instron tensile test system at 90 ^oC in controlled conditions of stretching, above glass transition temperature of both, polymer forming matrix and particles. Finally, particles were liberated from the polymer matrix by repeated sedimentation and washing with di. water. The spheroidal particles with aspect ratio (AR) in the range 2-7 were obtained and the obtained ARs were directly proportional to the film elongation. The spheroids longer axis was in the range from 5.2 μm to 11.9 μm depending on the extension of the particles. The progress of particles degradation in aqueous environment (pH=7.4, ionic strength=0.02 mol/L, T=37.0 ±0.5 ^oC) was monitored using SEM, GPC and gravimetric analysis. SEM images and GPC analysis of particles molecular mass were registered every 7 days of degradation progress. It was found that elongation of spherical particles and particles aspect ratio affected time of particles degradation. The degradation time increased with increasing particles aspect ratio. Moreover, the results of the studies revealed that the spherical and spheroidal particles degraded according to different mechanisms. The different mechanism of hydrolysis of the spheroidal particles was related to the reorganization of the polymer chains in the surface layer of the particles during their stretching at temperature above T_g.

Acknowledgements.

The studies were financially supported by National Science Centre (Poland) grant, UMO-2018/29/B/ST8/01721.