A biodegradable, injectable, gel system based on MPEG-b-(PCL-ran-PLLA) diblock copolymers with an adjustable therapeutic window.
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 < or = 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.
Kang
Yun Mi
YM
Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea.
Lee
Sang Hyo
SH
Lee
Ju Young
JY
Son
Jin Soo
JS
Kim
Byung Soo
BS
Lee
Bong
B
Chun
Heung Jae
HJ
Min
Byoung Hyun
BH
Kim
Jae Ho
JH
Kim
Moon Suk
MS
D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis*; D002850:Chromatography, Gel; D003460:Crystallization; D005455:Fluorescent Antibody Technique; D005782:Gels; D020007:Implants, Experimental; D007267:Injections; D019344:Lactic Acid / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D044367:Phase Transition; D011091:Polyesters / Q000138:chemical synthesis*; D011092:Polyethylene Glycols / Q000138:chemical synthesis*; D011108:Polymers / Q000138:chemical synthesis*; D051381:Rats; D012996:Solutions; D013194:Staining and Labeling; D013696:Temperature; D014783:Viscosity; D014867:Water / Q000737:chemistry
D001672:Biocompatible Materials; D005782:Gels; D011091:Polyesters; D011108:Polymers; D012996:Solutions; D014867:Water; C016240:polycaprolactone; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); C028210:monomethoxypolyethylene glycol