Polyelectrolyte complex micelles by self-assembly of polypeptide-based triblock copolymer for doxorubicin delivery

• Published in: Asian journal of pharmceutical sciences 2014-08, Vol.9 (4), p.191-198
• Main Authors: Kim, Jeong Hwan, Ramasamy, Thiruganesh, Tran, Tuan Hiep, Choi, Ju Yeon, Cho, Hyuk Jun, Yong, Chul Soon, Kim, Jong Oh
• Format: Article
• Language: English
• Subjects: Drug delivery; Micelles; Poly(ethylene glycol); Poly(l-aspartic acid); Polyelectrolyte
• ISSN: 1818-0876; 2221-285X
• DOI: 10.1016/j.ajps.2014.05.001

Polyelectrolyte complex micelles were prepared by self-assembly of polypeptide-based triblock copolymer as a new drug carrier for cancer chemotherapy. The triblock copolymer, poly(l-aspartic acid)-b-poly(ethylene glycol)-b-poly(l-aspartic acid) (PLD-b-PEG-b-PLD), spontaneously self-assembled with doxorubicin (DOX) via electrostatic interactions to form spherical micelles with a particle size of 60–80 nm (triblock ionomer complexes micelles, TBIC micelles). These micelles exhibited a high loading capacity of 70% (w/w) at a drug/polymer ratio of 0.5 at pH 7.0. They showed pH-responsive release patterns, with higher release at acidic pH than at physiological pH. Furthermore, DOX-loaded TBIC micelles exerted less cytotoxicity than free DOX in the A-549 human lung cancer cell line. Confocal microscopy in A-549 cells indicated that DOX-loaded TBIC micelles were transported into lysosomes via endocytosis. These micelles possessed favorable pharmacokinetic characteristics and showed sustained DOX release in rats. Overall, these findings indicate that PLD-b-PEG-b-PLD polypeptide micelles are a promising approach for anti-cancer drug delivery.