The Chemotherapeutic Potential of Doxorubicin-Loaded Peg-B-Plga Nanopolymersomes in Mouse Breast Cancer Model Publisher Pubmed



Alibolandi M¹ ; Sadeghi F^{2, 3} ; Abnous K⁴ ; Atyabi F⁵ ; Ramezani M^{4, 6} ; Hadizadeh F¹ Show Affiliations
Source: European Journal of Pharmaceutics and Biopharmaceutics Published:2015

Abstract

Abstract 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 ± 1.2 nm 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 = 1.76 μg/mL) than did DOX-loaded nanopolymersomes (15.82 μg/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. © 2015 Elsevier B.V.