Preparation, characterization and biodistribution of the lactone form of 10-hydroxycamptothecin (HCPT)-loaded bovine serum albumin (BSA) nanoparticles.

10-Hydroxycamptothecin (HCPT) is insoluble in both water and physiological acceptable organic solvents and tends to change into its carboxylate form, which shows minimal anticancer activity and several unpredictable side effects. The goal of this study is to exploit an appropriate delivery system for HCPT to improve the stability of its lactone form. Bovine serum albumin (BSA) nanoparticles entrapping HCPT were prepared by reformative emulsion-heat stabilization technique. During this process, HCPT transformed from lactone to carboxylate and finally back to lactone form successfully. A simple reversed-phased HPLC method was developed to analyze both lactone and carboxylate forms of HCPT synchronously. Mean particle size and the ratio of lactone and carboxylate forms of HCPT were evaluated to investigate the effects of the formulations and preparation conditions. It was indicated the percentage of lactone form of HCPT in resultant BSA nanoparticles could be improved over 95% through adjusting the concentration of NaOH solution and the stirring time after high-speed emulsification. This drug delivery system was also characterized by dynamic light scattering (DLS) and light microscopy. The investigations on drug loading, in vitro release and body distribution in rats after intravenous (i.v.) administration were also carried out. It was found that the obtained nanoparticles showed spherical shape with the mean particle size of around 600 nm, and drug loading content, encapsulation efficiency and yield achieved 2.21%, 57.5% and 90.5% with the optimal preparation conditions, respectively. The in vitro release behavior exhibited a sustaining release manner and was affected by the trypsin in medium. HCPT could release more than 90% within 20 h in the medium of pH 7.4 PBS containing 750 U/ml trypsin, but only 25% within 40 h in the pure pH 7.4 PBS. The results of body distribution study in rats showed the liver targeting potential of HCPT-BSA nanoparticles that 59.6%, 52.9% and 55.3% of the examined amount of lactone HCPT accumulated in livers at 1, 4 and 24h after injection, respectively. These results suggest that the HCPT-BSA nanoparticles seem to be a stable delivery system for poorly soluble HCPT or its derivatives.