Enzymatically degradable temperature-sensitive polypeptide as a new in-situ gelling biomaterial.
We are reporting a poly (ethylene glycol)-block-poly(alanine-co-phenyl alanine) (PEG-PAF) aqueous solution that undergoes sol-to-gel transition as the temperature increases. The sol-to-gel transition was observed at as low a concentration as 3.0-7.0 wt.%. Micellar aggregation accompanying small conformational changes of the peptide from random coils to beta-sheets is suggested as the sol-to-gel transition mechanism of the PEG-PAF aqueous solution. The PEG-PAF is stable in phosphate buffered saline, however, it degraded in the subcutaneous layer of rats. In vitro study showed that proteolytic enzymes such as cathepsin B, cathepsin C, and elastase that are present in the subcutaneous layer of the mammalian tissue might be responsible for the degradation of the polymer in rats. As a feasibility study of this material, a single shot of an aqueous insulin formulation (13.8 mg insulin/kg) showed a hypoglycemic effect over 18 days in rats. The current functional polypeptide may be very promising as an in-situ gelling system for tissue engineering, cell/stem cell therapy, and drug delivery.
Jeong
Yuri
Y
Department of Chemistry and Nano Science, Ewha Womans University, Daehyun-Dong, Seodaemun-Ku, Seoul, 120-750, Republic of Korea.
Joo
Min Kyung
MK
Bahk
Kyung Hyun
KH
Choi
Yun Young
YY
Kim
Ho-Tae
HT
Kim
Won-Ki
WK
Lee
Hwa Jeong
HJ
Sohn
Youn Soo
YS
Jeong
Byeongmoon
B
D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry*; D001673:Biodegradation, Environmental; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005240:Feasibility Studies; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage; D008823:Micelles; D015394:Molecular Structure; D008970:Molecular Weight; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry*; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D011487:Protein Conformation; D051381:Rats; D012996:Solutions; D050151:Subcutaneous Fat / Q000201:enzymology / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry
D001672:Biocompatible Materials; D005782:Gels; D007004:Hypoglycemic Agents; D007328:Insulin; D008823:Micelles; D010455:Peptides; D011108:Polymers; D012996:Solutions; D014867:Water; C019529:polyalanine; C012001:polyphenylalanine; D011092:Polyethylene Glycols