Biodegradability and biocompatibility of a pH- and thermo-sensitive hydrogel formed from a sulfonamide-modified poly(epsilon-caprolactone-co-lactide)-poly(ethylene glycol)-poly(epsilon-caprolactone-co-lactide) block copolymer.
A pH- and thermo-sensitive block copolymer was synthesized by adding pH-sensitive sulfamethazine oligomers (SMOs) to either end of a thermo-sensitive poly(epsilon-caprolactone-co-lactide)-poly(ethylene glycol)-poly(epsilon-caprolactone-co-lactide) (PCLA-PEG-PCLA) block copolymer. The resulting pH- and thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer solution did not form a gel at high pH (pH 8.0) or at increased temperatures (ca. 70 degrees C), but did form a stable gel under physiological conditions (pH 7.4 and 37 degrees C). The degradation rate of the pH- and thermo-sensitive block copolymer decreased substantially compared with the control block copolymer of PCLA-PEG-PCLA, due to the buffering effect of the SMO-PCLA-PEG-PCLA-SMO sulfonamide groups on the acidic monomer-induced rapid degradation of PCLA-PEG-PCLA. This suitable sol-gel transition and sustained biodegradability of the pH- and thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer resolves two of the major drawbacks associated with thermo-sensitive block copolymers, namely premature gelation and rapid degradation. Interestingly, SMO-PCLA-PEG-PCLA-SMO showed no evidence of cytotoxicity in vitro. However, subcutaneous injection of the pH- and thermo-sensitive block copolymer solution (20wt% in PBS at pH 8.0) into Sprague-Dawley (SD) rats resulted in rapid, stable gel formation, with the injected hydrogel being completely degraded in vivo in just 6 weeks. The injected hydrogel in vivo presented a typical acute inflammation within 2 weeks, although chronic inflammation was not observed during the first 6-week period. As such, the pH- and thermo-sensitive hydrogel of the SMO-PCLA-PEG-PCLA-SMO block copolymer is a suitable candidate for use in drug delivery systems and cell therapy.
Shim
Woo Sun
WS
Department of Polymer Science & Engineering, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
Kim
Jong-Ho
JH
Park
Hungkyu
H
Kim
Kwangmeyung
K
Chan Kwon
Ick
I
Lee
Doo Sung
DS
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D001673:Biodegradation, Environmental; D002208:Caproates / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D006358:Hot Temperature; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D006863:Hydrogen-Ion Concentration; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D011091:Polyesters / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions / Q000737:chemistry; D013696:Temperature
D001672:Biocompatible Materials; D002208:Caproates; D020100:Hydrogels; D007783:Lactones; D011091:Polyesters; D012996:Solutions; C121056:caprolactone; C062968:lactide-caprolactone copolymer