Effect of Different Tensoactives on the Morphology and Release Kinetics of PLA-b-PEG Microcapsules Loaded With the Natural Anticancer Compound Perillyl Alcohol

Abstract

Perillyl alcohol is a natural compound that has attracted a significant interest due to its potent antitumor activity. However, clinical trials have exhibited poor tolerance by oral administration, mainly due to gastrointestinal side effects. We propose the entrapment of perillyl alcohol into poly(D,L-lactic acid)-block-poly(ethylene glycol) (PLA-b-PEG) as delivery platform (entrapment efficiency of 63%-68%). The influence of different concentrations of the tensoactives poly(vinyl alcohol) and sodium cholate (SC) on shear strength and morphology was evaluated by confocal laser scanning microscopy and interfacial tension studies. Only the microcapsules formulated with SC maintained their sphericity when submitted to shear stress. These results indicate that the interface is better organized with SC, conferring mutual stacked packing that is able to better stabilize the organic drop. The in vitro release profile of the drug from the microcapsules was correlated with pore formation and polymer degradation, best fitted to the Baker-Lonsdale model. The loaded microcapsules showed an IC₅₀ equivalent to that of the free drug (80 μg/mL) after 72 h of exposure. However, after 24 h of exposure, loaded microcapsules showed an IC₅₀ almost two-fold higher (220 μg/mL) suggesting gradual release.

Keywords: biodegradable polymer; controlled release; kinetics; microencapsulation; polylactide acid (PLA); polymeric drug delivery system; surfactant.