title: Stable thermosensitive in situ gel-forming systems based on the lyophilizate of chitosan/α,β-glycerophosphate salts.
abstract: In the present study, lyophilization was attempted to improve the long-term storage of CS/GP thermogelling systems for biopharmaceutical applications. After lyophilization, CS/α,β-GP lyophilizate could not be dissolved in water, but some metal salts, such as NaCl, CaCl2, and MgCl2 surprisingly facilitated its dissolution. X-ray powder diffraction analysis suggested that calcium ions might preferentially form salts with α,β-GP, inhibit the transfer of protons from CS to α,β-GP, and then inhibit the aggregation of CS molecules during lyophilization. Comparison of the freshly prepared CS/α,β-GP/salt solutions and the reconstituted solutions from lyophilizates showed that lyophilization clearly influenced the properties of reconstituted CS/α,β-GP/salt solutions such as gelation time, viscosity, and pH. Furthermore, the reconstituted CS/α,β-GP/CaCl2 solutions maintained thermogelling properties and formed hydrogels at 37°C within approximately 5min, but did not form hydrogels at 20°C and 4°C over 2 weeks. The model protein bovine serum albumin (BSA) was further incorporated into the CS/α,β-GP/CaCl2 system. In vitro release experiments showed the sustained release of BSA from CS/α,β-GP/CaCl2 hydrogels in a pH-sensitive manner, demonstrating that CS/α,β-GP/CaCl2 may be useful as an in situ gel-forming system.
authors.affiliation: College of Life Science, Hebei Normal University, No. 20 Road East of 2nd Ring South, Shijiazhuang City, Hebei Province 050024, People's Republic of China.
authors.forename: Guanghao
authors.initials: G
authors.lastname: Wu
authors.affiliation: College of Life Science, Hebei Normal University, No. 20 Road East of 2nd Ring South, Shijiazhuang City, Hebei Province 050024, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: College of Life Science, Hebei Normal University, No. 20 Road East of 2nd Ring South, Shijiazhuang City, Hebei Province 050024, People's Republic of China. Electronic address: 576477418@qq.com.
authors.forename: Jintian
authors.initials: J
authors.lastname: He
authors.affiliation: College of Life Science, Hebei Normal University, No. 20 Road East of 2nd Ring South, Shijiazhuang City, Hebei Province 050024, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Life Science, Hebei Normal University, No. 20 Road East of 2nd Ring South, Shijiazhuang City, Hebei Province 050024, People's Republic of China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Dai
authors.affiliation: College of Life Science, Hebei Normal University, No. 20 Road East of 2nd Ring South, Shijiazhuang City, Hebei Province 050024, People's Republic of China. Electronic address: zhaobaohua86178@sohu.com.
authors.forename: Baohua
authors.initials: B
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002417:Cattle; D065546:Drug Liberation / Q000502:physiology; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods; D005994:Glycerophosphates / Q000737:chemistry* / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry* / Q000378:metabolism; D012492:Salts; D012710:Serum Albumin, Bovine; D014961:X-Ray Diffraction
chemical_list: D005994:Glycerophosphates; D020100:Hydrogels; D012492:Salts; D012710:Serum Albumin, Bovine; C029620:alpha-glycerophosphoric acid; C031463:beta-glycerophosphoric acid
keywords: Chitosan; Glycerophosphate; Hydrogel; Lyophilization; Stability