A biodegradable, injectable, gel system based on MPEG- b -(PCL- ran -PLLA) diblock copolymers with an adjustable therapeutic window

• Published in: Biomaterials 2010-03, Vol.31 (9), p.2453-2460
• Main Authors: Kang, Yun Mi, Lee, Sang Hyo, Lee, Ju Young, Son, Jin Soo, Kim, Byung Soo, Lee, Bong, Chun, Heung Jae, Min, Byoung Hyun, Kim, Jae Ho, Kim, Moon Suk
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Biocompatible Materials - chemical synthesis; Chromatography, Gel; Crystallization; Degradation; Dentistry; Fluorescent Antibody Technique; Gels; Implants, Experimental; In situ-forming gel; Injections; Lactic Acid - chemical synthesis; Magnetic Resonance Spectroscopy; MPEG- b-(PCL- ran-PLLA) diblock copolymer; Phase Transition; Polyesters - chemical synthesis; Polyethylene Glycols - chemical synthesis; Polymers - chemical synthesis; Rats; Solutions; Staining and Labeling; Temperature; Viscosity; Water - chemistry
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2009.11.115

Abstract In situ-forming gel systems have drawn increasing attention for their potential use in a variety of biomedical applications. Here, we examined an in situ-forming gel system comprised of MPEG- b -PCL and MPEG- b -(PCL- ran -PLLA) diblock copolymers with different PLLA contents (0–10 mol%) in the PCL segment. The crystalline region of the PCL- ran -PLLA segment decreased with increasing PLLA content. The MPEG- b -(PCL- ran -PLLA) diblock copolymer solutions were liquid at room temperature and only MPEG- b -(PCL- ran -PLLA) diblock copolymer solutions with a PLLA content ≤5 mol% in the PCL segment showed a sol-to-gel transition as the temperature was increased. The viscosity change associated with sol-to-gel phase transition depended on the PLLA content in the PCL segment. A MPEG- b -PCL diblock copolymer solution incubated in vitro showed increasing viscosity without degradation, whereas the viscosity of MPEG- b -(PCL- ran -PLLA) diblock copolymer solutions continuously and sharply decreased with increasing PLLA content in the PCL segment. As the amount of PLLA increased, the size of in vivo-formed MPEG- b -(PCL- ran -PLLA) gels after initial injection tended to gradually decrease because of hydrolytic degradation of the PLLA in the PCL- ran -PLLA segment. An immunohistochemical examination showed that in vivo MPEG- b -(PCL- ran -PLLA) diblock copolymer gels provoked only a modest inflammatory response. Collectively, our results show that the MPEG- b -(PCL- ran -PLLA) diblock copolymer gel described here could serve as a minimally invasive, therapeutic, in situ-forming gel system that offers an experimental window adjustable from a few weeks to a few months.