The chemotherapeutic potential of doxorubicin-loaded PEG-b-PLGA nanopolymersomes in mouse breast cancer model

• DOI: 10.1016/j.ejpb.2015.07.005
• Publication Date: 2015-07-11T04:33:21Z
• Authors: Mona Alibolandi; Fatemeh Sadeghi; Khalil Abnous; Fatemeh Atyabi; Mohammad Ramezani; Farzin Hadizadeh
• Keywords: 0301 basic medicine; Drug Carriers; Mice, Inbred BALB C; Antibiotics, Antineoplastic; Cell Survival; Surface Properties; Drug Compounding; Polyesters; Mammary Neoplasms, Experimental; Polyethylene Glycols; 3. Good health; 03 medical and health sciences; Drug Stability; Microscopy, Electron, Transmission; Doxorubicin; Cell Line, Tumor; Animals; Nanoparticles; Particle Size

Vesicles of mPEG-PLGA block copolymer were developed to deliver a therapeutic quantity of doxorubicin (DOX) for breast cancer treatment. The DOX-loaded nanoparticles (NPs) were prepared by the pH-gradient method and then evaluated in terms of morphology, size, DOX encapsulation efficiency and in vitro drug release mechanism. The PEG-PLGA nanopolymersomes were 134±1.2nm spherical NPs with a narrow size distribution (PDI=0.121). DOX was entrapped in mPEG-PLGA nanopolymersomes with an encapsulation efficiency and a loading content of 91.25±4.27% and 7.3±0.34%, respectively. The DOX-loaded nanopolymersomes were found to be stable, demonstrating no significant change in particle size and encapsulation efficiency (EE%) during the 6-month storage period of the lyophilized powder at 4°C. The nanopolymersomes sustained the release of DOX. In cytotoxicity studies of 4T1 cell line samples, free DOX showed a higher cytotoxicity (IC50=1.76μg/mL) than did DOX-loaded nanopolymersomes (15.82μg/mL) in vitro. In order to evaluate the antitumor efficacy and biodistribution of DOX-loaded nanopolymersomes, murine breast tumors were established on the BALB/c mice, and in vivo studies were performed. The obtained results demonstrated that the prepared drug delivery system was highly effective against a murine breast cancer tumor model and successfully accumulated in the tumor site through an enhanced permeation and retention mechanism. In vivo studies also proved that DOX-loaded nanopolymersomes are stable in blood circulation and could be considered a promising and effective DOX delivery system for breast cancer treatment.