title: Thermogelling chitosan-g-(PAF-PEG) aqueous solution as an injectable scaffold.
abstract: The present study reports on a thermogelling poly(ethylene glycol)-poly(L-alanine-co-L-phenyl alanine) grafted chitosan (CS-g-(PAF-PEG)) system, focusing on phase diagram, transition mechanism, and in vivo gel duration. The sol-to-gel transition temperature decreased from 27 to 11 °C as the concentration increased from 4.0 wt % to 9.0 wt %. The polymer formed micelles with 10-50 nm in diameter at 10 °C and formed large aggregates ranging from hundreds to thousands of nanometers in size as the temperature increased from 10 to 35 °C, suggesting that an extensive molecular aggregation might be involved in the sol-to-gel transition. To study the transition mechanism on a molecular level, we investigated pH, circular dichroism spectra, and (13)C NMR spectra of the CS-g-(PAF-PEG) aqueous solution as a function of temperature. As the temperature increased, deprotonation of the chitosan and dehydration of the PEG were suggested, whereas the α-helical secondary structure of PAF was slightly changed in the sol-to-gel transition temperature range of 10-50 °C. A gel was formed in situ after injecting the CS-g-(PAF-PEG) aqueous solution into the subcutaneous layer of rats. About 60-70% of the gel was eliminated in 1 week, and the remaining gel was completely cleared from the implant site in 14 days. The results indicate the potential of CS-g-(PAF-PEG) as a promising short-term carrier for pharmaceutical agents.
authors.affiliation: Department of Bioinspired Science (WCU), Ewha Womans University, Seoul, Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kang
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Moon
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Joo
authors.forename: Byeongmoon
authors.initials: B
authors.lastname: Jeong
mesh_terms: D000818:Animals; D048271:Chitosan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002942:Circular Dichroism; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007267:Injections; D046911:Macromolecular Substances / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D012996:Solutions; D013696:Temperature; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D046911:Macromolecular Substances; D010455:Peptides; D012996:Solutions; C578194:poly(ethylene glycol)-poly(alanine-co-phenyl alanine) grafted chitosan; D014867:Water; D011092:Polyethylene Glycols; D048271:Chitosan