Tamibarotene-Loaded PLGA Microspheres for Intratumoral Injection Administration: Preparation and Evaluation.

ABSTRACT

Tamibarotene (Am80) has good curative effect on advanced hepatocellular carcinoma (HCC). To improve the therapeutic efficacy furtherly, we prepared tamibarotene-loaded PLGA microspheres (Am80-PLGA-MS) for intratumoral injection. Firstly, Am80-PLGA-MS were prepared by emulsion-solvent evaporation method. Subsequently, microspheres were characterized by particle size analysis, drug loading (DL), and entrapment efficiency (EE). Finally, the drug release characteristics in vitro, pharmacokinetic, and pharmacodynamics were studied separately. According to results obtained, microspheres were spherical with a uniform particle size 7.04 ± 0.03 µm and its EE and DL were 82.23 ± 0.74 and 11.74 ± 0.11%, respectively. In vitro, Am80-PLGA-MS can release drug for 14 days and its release behavior was fitted with the Higuchi equation. In pharmacokinetic studies, the t1/2ß, MRT, and AUC of microspheres were 15.43-fold, 8.62-fold, and 9.98-fold those of Am80 solution, respectively, which revealed that the utilization of drug was improved obviously. The pharmacodynamics studies showed that the tumor doubling time, growth inhibition rate, and specific growth rate of tumor of Am80-PLGA-MS were 1.34 times, 2.63 times, and 0.72 times those of drug solution, respectively, indicating that the inhibitory effect on tumor by the microspheres was significantly improved. In summary, Am80-PLGA-MS are promising carrier to enhance the inhibitory effect on tumor, which will provide significantly clinical value for treatment of HCC.