In vivo evaluation of doxorubicin-loaded (PEG)(3)-PLA nanopolymersomes (PolyDoxSome) using DMBA-induced mammary carcinoma rat model and comparison with marketed LipoDox™.
OBJECTIVE
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 h*μg/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 h*μg/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™.
Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research, S.A.S. Nagar, Mohali 160062, Punjab, India.
Wubeante Yenet
WY
Ayen
Neeraj
N
Kumar
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002273:Carcinogens / Q000633:toxicity*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004337:Drug Carriers; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D053758:Nanoparticles; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D002273:Carcinogens; D004337:Drug Carriers; D015127:9,10-Dimethyl-1,2-benzanthracene; D004317:Doxorubicin