Preparation and in vitro/in vivo evaluation of doxorubicin-loaded poly[lactic-co-glycol acid] microspheres using electrospray method for sustained drug delivery and potential intratumoral injection

Colloids and Surfaces. B, Biointerfaces
Ming-Yi HsuShih-Jung Liu

Abstract

For cancer treatment, intratumoral drug injection has many limitations and not commonly adopted. The poly[lactic-co-glycolic acid] (PLGA) has emerged as a promising vehicle to enhance the in vitro/in vivo characteristic of various drugs. We prepared doxorubicin-PLGA microspheres (DOX-PLGA MSs) using the electrospray method. An in vitro elution method was employed to evaluate the release of DOX from the MSs. We performed an in vivo study on rats, in which we directly injected DOX-PLGA MSs into the liver. We measured liver and plasma DOX concentrations to assess local retention and systemic exposure. The mean diameter of the MSs was 6.74 ± 1.01 μm. The in vitro DOX release from the MSs exhibited a 12.3 % burst release on day 1, and 85.8 % of the drug had been released after 30 days. The in vivo tests revealed a higher local drug concentration at the target lobe of the liver than at the adjacent median lobe. In the first week, the DOX concentration in the peripheral blood of the MS group was lower than that of the direct DOX injection group. Based on the measured intrahepatic concentration and plasma pharmacokinetic profiles, DOX-PLGA MSs could be suitable vectors of chemotoxic agents for intratumoral injection.

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