Biodegradability and biocompatibility of a pH- and thermo-sensitive hydrogel formed from a sulfonamide-modified poly(ε-caprolactone-co-lactide)-poly(ethylene glycol)-poly(ε-caprolactone-co-lactide) block copolymer

Woo Sun Shim, Jong Ho Kim, Hungkyu Park, Kwang Meyung Kim, Ick Chan Kwon, Doo Sung Lee

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

A pH- and thermo-sensitive block copolymer was synthesized by adding pH-sensitive sulfamethazine oligomers (SMOs) to either end of a thermo-sensitive poly(ε-caprolactone-co-lactide)-poly(ethylene glycol)-poly(ε-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 °C), but did form a stable gel under physiological conditions (pH 7.4 and 37 °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 (20 wt% 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.

Original languageEnglish
Pages (from-to)5178-5185
Number of pages8
JournalBiomaterials
Volume27
Issue number30
DOIs
Publication statusPublished - 2006 Oct 1
Externally publishedYes

Fingerprint

Ethylene Glycol
Hydrogel
Biodegradability
Sulfonamides
Sulfamethazine
Biocompatibility
Oligomers
Hydrogels
Polyethylene glycols
Block copolymers
Gels
Degradation
dilactide
polycaprolactone
poly(lactide)
Gelation
Cytotoxicity
Inflammation
Sol-gels
Rats

Keywords

  • Biocompatibility
  • Biodegradability
  • pH- and thermo-sensitive hydrogel
  • Sulfonamide-modified block copolymer

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

Cite this

Biodegradability and biocompatibility of a pH- and thermo-sensitive hydrogel formed from a sulfonamide-modified poly(ε-caprolactone-co-lactide)-poly(ethylene glycol)-poly(ε-caprolactone-co-lactide) block copolymer. / Shim, Woo Sun; Kim, Jong Ho; Park, Hungkyu; Kim, Kwang Meyung; Kwon, Ick Chan; Lee, Doo Sung.

In: Biomaterials, Vol. 27, No. 30, 01.10.2006, p. 5178-5185.

Research output: Contribution to journalArticle

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T1 - Biodegradability and biocompatibility of a pH- and thermo-sensitive hydrogel formed from a sulfonamide-modified poly(ε-caprolactone-co-lactide)-poly(ethylene glycol)-poly(ε-caprolactone-co-lactide) block copolymer

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AU - Kim, Jong Ho

AU - Park, Hungkyu

AU - Kim, Kwang Meyung

AU - Kwon, Ick Chan

AU - Lee, Doo Sung

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N2 - A pH- and thermo-sensitive block copolymer was synthesized by adding pH-sensitive sulfamethazine oligomers (SMOs) to either end of a thermo-sensitive poly(ε-caprolactone-co-lactide)-poly(ethylene glycol)-poly(ε-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 °C), but did form a stable gel under physiological conditions (pH 7.4 and 37 °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 (20 wt% 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.

AB - A pH- and thermo-sensitive block copolymer was synthesized by adding pH-sensitive sulfamethazine oligomers (SMOs) to either end of a thermo-sensitive poly(ε-caprolactone-co-lactide)-poly(ethylene glycol)-poly(ε-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 °C), but did form a stable gel under physiological conditions (pH 7.4 and 37 °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 (20 wt% 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.

KW - Biocompatibility

KW - Biodegradability

KW - pH- and thermo-sensitive hydrogel

KW - Sulfonamide-modified block copolymer

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