In vivo evaluation of doxorubicin-loaded (PEG)(3)-PLA nanopolymersomes (PolyDoxSome) using DMBA-induced mammary carcinoma rat model and comparison with marketed LipoDox™.

PURPOSE

To evaluate in vivo doxorubicin-loaded (PEG)(3)-PLA nanopolymersomes (PolyDoxSome) using 7,12-dimethyl benz[α]anthracene (DMBA)-induced mammary carcinoma rat model compared to marketed formulation LipoDox™.

METHODS

Sprague Dawley female rats with mean tumor volume of about 2 cm(3) were used for pharmacokinetics, biodistribution, antitumor efficacy and toxicity studies.

RESULTS

This study demonstrates that PolyDoxSome has higher AUC (569 vs. 4 hμg/mL), longer plasma circulation half life (21.9 vs. 0.49 h), decreased clearance (10.5 vs. 1579 mL/h/kg) and volume of distribution (137.7 vs. 1091 mL/kg) as compared to free doxorubicin. Tissue distribution profile showed increased doxorubicin concentration in tumor and decreased concentration in heart as compared to free doxorubicin. The toxicity studies as measured from liver function tests, cardiac enzyme assays, hematology test and body weight has demonstrated that it is better tolerated than free doxorubicin. When PolyDoxSome was compared with LipoDox™, it differs in size (171 vs. <100 nm), plasma circulation half life (22 vs. 35 h), C(max) (34 vs. 67 μg/mL), and AUC (568 vs. 2291 hμg/mL), however PolyDoxSome was comparable on efficacy and toxicity profile of LipoDox™.

CONCLUSIONS

Results suggest that PolyDoxSome has better in vivo profile than free doxorubicin and comparable efficacy and toxicity to LipoDox™.