Abbott Laboratories, in collaboration with Shenyang Pharmaceutical University, China, and Philipps-University Marburg, Germany, has studied PLGA microspheres loading hydrophobic drug atrasentan (ABT627), an endothelin receptor A antagonist in development by Abbott for the treatment of prostate cancer.

Countless research articles are focused on microencapsulation of hydrophilic drug substances, such as proteins and peptides, in poly(lactic-co-glycolic) acid (PLGA) matrices. However, scarce investigations are available regarding PLGA microparticles loading lipophilic active principles. The present study concentrates on the effects of various process parameters on the internal morphology of ABT627-loaded PLGA microspheres, prepared by a conventional oil-in-water (O/W) microencapsulation method.

From the cross-sectional scanning electron microscopy (SEM) images of the microspheres, it seemed clear that the internal phase of the microspheres was continuous phase/dispersed phase ratio-dependent, the porosity being inversely proportional to the continuous phase/dispersed phase ratio. At a particular continuous phase/dispersed phase ratio, the microspheres showed a core/shell structure.

Following ABT627-loaded PLGA microspheres in vitro incubation, drug release showed a biphasic pattern. Internal morphology did not change during the first 13 days of ABT627 release, suggesting that the main release mechanism was diffusion. During the following 17 days, internal morphology observation evidenced that micropheres were degraded by auto-catalyzation from the inside of the matrix.

A stated by the authors, hydrophobic drugs release from PLGA microspheres is highly dependent on the internal morphology of the particles.

Source: Mao S, Shi Y, Li L, Xu J, Schaper A, Kissel T. European Journal of Pharmaceutics and Biopharmaceutics 68 (2008) 214-223