PLA nanoparticles loaded with an active lactone form of hydroxycamptothecin: Development, optimization, and in vitro-in vivo evaluation in mice bearing H22 solid tumor

Hydroxycamptothecin (HCPT)-loaded PLA nanoparticles were prepared by a one-step method using the direct dialysis technique, and were examined for particle characteristics, in vitro drug release, and cytotoxicity, as well as antitumor efficiency. Three main influential factors based on the results of a single-factor test, i.e., PLA concentration, ratio of HCPT to PLA (wt/wt), and dialysis bags with different molecule weight cutoffs, were evaluated using an orthogonal design, giving nanoparticles an average diameter of ∼226.8 nm with smooth surface, modest drug entrapment efficiency (65.15%), and fine drug-loading content (5.16%, w/w). HCPT was in a crystalline state within the particles. In vitro drug release studies exhibited a slow and prolonged release profile over a period of 30 days. The cytotoxicity test on BEL-7402 cells indicated that the HCPT-PLA nanoparticles were more cytotoxic than commercially available HCPT injection. When the antitumor effect was examined by i.v. administration to mice bearing H22 solid tumor, HCPT-PLA nanoparticles showed a significant suppression of tumor growth without loss of body weight. These results suggest that HCPT-PLA nanoparticles prepared by the dialysis technique present desirable characteristics for sustained drug delivery and are potentially useful to enhance the antitumor efficacy of HCPT.