Preparation and characterization of poly(lactic-co-glycolic acid) microspheres loaded with a labile antiparkinson prodrug

作者：D'Aurizio E; van Nostrum C F; van Steenbergen M J; Sozio P; Siepmann F; Siepmann J; Hennink W E; Di Stefano A^*

来源：International Journal of Pharmaceutics, 2011, 409(1-2): 289-296.

DOI：10.1016/j.ijpharm.2011.02.036

• Parkinson's disease
• L-Dopa-alpha-lipoic acid
• Hydrolysis kinetics
• PLGA microspheres
• Release

L-Dopa-alpha-lipoic acid (LD-LA) is a new multifunctional prodrug for the treatment of Parkinson's disease. In human plasma, LD-LA catechol esters and amide bonds are chemically and enzymatically cleaved, respectively, resulting in a half-life time of about fifty minutes. In the present work, the unstable LD-LA was entrapped into biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres designed as depot systems to protect this prodrug against degradation and to obtain a sustained release of the intact compound. The microspheres were prepared by an oil-in-water emulsion/solvent evaporation technique and the effect of formulation and processing parameters (polymer concentration in the organic solvent, volumes ratio of the phases, rate of the organic solvent evaporation) on microspheres characteristics (size, loading, morphology, release) was investigated. Also emphasis was given on the stability of the drug before and after release as well as on the underlying mass transport mechanisms controlling LD-LA release. Interestingly, when encapsulated in appropriate conditions into PLGA microspheres, the labile prodrug was stabilized and released via Fickian diffusion up to more than one week.

• 出版日期2011-5-16