title: Synthesis, characterization, biodegradability and biocompatibility of a temperature-sensitive PBLA-PEG-PBLA hydrogel as protein delivery system with low critical gelation concentration.
abstract: Temperature-sensitive hydrogels were designed using a series of A-B-A triblock copolymers consisting of poly (ethylene glycol) (PEG) with different molecular weights as the hydrophilic block B and poly (β-butyrolactone-co-lactic acid)(PBLA) with varying block lengths and composition as the hydrophobic block A. The triblock copolymers were synthesized by ring-opening polymerization (ROP) of β-BL and LA in bulk using PEG as an initiator and Sn(Oct)2 as the catalyst. Their chemical structure and molecular characteristics were determined by NMR, GPC and DSC, and the relationship between structure and phase behaviors in aqueous solutions was investigated as well. It was found that the phase behaviors in aqueous solutions including critical micelle concentration (CMC), sol-gel-sedimentation phase transition temperature, gel window width and critical gelation concentration (CGC) are largely dependent on the molecular weight and block length ratio of PEG/PBLA. Most importantly, they show a very low CGC ranging from 4 to 8 wt% because of the introduction of β-BL. Furthermore, the biodegradability and biocompatibility of the hydrogels were evaluated. Finally, lysozyme as a model protein was used to evaluate the ability to deliver protein drugs in a sustained release manner and biologically active form. All results demonstrated that the temperature-sensitive in situ forming hydrogel has a promising potential as sustained delivery system for protein drugs.
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University , Nanjing , China.
authors.forename: Yourui
authors.initials: Y
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Yerong
authors.initials: Y
authors.lastname: Xiong
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.forename: Chunmeng
authors.initials: C
authors.lastname: Sun
authors.forename: Ammar
authors.initials: A
authors.lastname: Ouahab
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Tu
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001673:Biodegradation, Environmental; D003692:Delayed-Action Preparations / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008823:Micelles; D008970:Molecular Weight; D009113:Muramidase / Q000737:chemistry*; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions / Q000737:chemistry; D013696:Temperature
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D008823:Micelles; D011108:Polymers; D012996:Solutions; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C013426:beta-butyrolactone; D019344:Lactic Acid; D011092:Polyethylene Glycols; D009113:Muramidase; D015107:4-Butyrolactone
keywords: Biocompatible; biodegradable; hydrogel; protein drugs; temperature-sensitive