In-vivo pharmacokinetics, tissue distribution and anti-tumour effect of hydroxycamptothecin delivered in oil-in-water submicron emulsions

Objectives The aim of this study was to investigate the pharmacokinetics, tissue distribution and anti-tumour effect of hydroxycamptothecin submicron emulsions (HCPT-SEs). Methods HCPT-SEs or HCPT injection (HCPT-I) was administered intravenously into the tail vein of rats or S180 tumour-bearing mice. Key findings HCPT-SEs increased the plasma concentration of HCPT compared with HCPT-I at all time points. The AUC0-8, elimination half-life and mean residence time of anionic submicron emulsions containing HCPT (HCPT-ASEs) and cationic submicron emulsions containing HCPT (HCPT-CSEs) were significantly greater than those of HCPT-I (P < 0.01). Especially, a prolonged elimination half-life was found for HCPT-CSEs. HCPT-CSEs and HCPT-ASEs resulted in a 7.9-fold and 3.1-fold increase in AUC0-6h of tumour compared with HCPT-I, respectively. The targeting efficiency (Te) of HCPT-ASEs and HCPT-CSEs indicated their selectivity to tumour and the Te of HCPT-CSEs was significantly higher than that of HCPT-ASEs (P < 0.01). The anti-tumour effect studies showed that HCPT-SEs improved the therapeutic efficiency of HCPT compared with HCPT-I. The percentage of tumour growth suppression rate of mice treated with HCPT-CSEs (2.0 mg HCPT eq./kg) increased 2.1 fold compared with that of HCPT-I. Conclusions Submicron emulsions can alter the pharmacokinetic characteristics and tissue distribution of HCPT, and enhance tumour targeting and anti-tumour activity.