Ketal containing amphiphilic block copolymer micelles as pH-sensitive drug carriers

• Published in: International journal of pharmaceutics Vol. 448; no. 1; pp. 259 - 266
• Main Authors: Lee, Iljae, Park, Minhyung, Kim, Yerang, Hwang, On, Khang, Gilson, Lee, Dongwon
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2013
• Subjects: Animals; antineoplastic agents; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - chemistry; Block copolymers; Camptothecin - administration & dosage; Camptothecin - chemistry; Cell Line, Tumor; Cell Survival - drug effects; composite polymers; cytosol; drug carriers; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug delivery; endosomes; ethylene glycol; Humans; Hydrogen-Ion Concentration; hydrophobicity; Ketal linkages; lysosomes; Mice; Micelles; NIH 3T3 Cells; pH-sensitive; Polyesters - administration & dosage; Polyesters - chemistry; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - chemistry; pH-sensitive; Drug delivery; Micelles; Ketal linkages; Block copolymers
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2013.03.017

pH-Responsive linkages have been widely exploited in the development of polymeric drug delivery systems, which trigger drug release selectively at tumor tissues or endosomes and lysosomes of cells. Herein we report new pH-sensitive amphiphilic poly(ketal adipate)-co-poly(ethylene glycol) block copolymers (PKA-PEG), which have acid-cleavable ketal linkages in their hydrophobic backbone. PKA-PEG copolymers self-assemble to form stable micelles with a mean diameter of ~175nm, which can encapsulate a payload of anticancer drugs and rapidly dissociate to release drug payload at the acid environment. The micelles are biocompatible and exhibit abilities to disrupt endosomes to enhance the cytosol drug delivery. Taken together, we anticipate that the pH-sensitive PKA-PEG micelles have great potential as anticancer drug carriers.