Stable thermosensitive in situ gel-forming systems based on the lyophilizate of chitosan/α,β-glycerophosphate salts

作者：Wu, Guanghao; Yuan, Yuan; He, Jintian^*; Li, Ying; Dai, Xiaojing; Zhao, Baohua^*

来源：International Journal of Pharmaceutics, 2016, 511(1): 560-569.

DOI：10.1016/j.ijpharm.2016.07.050

• Chitosan
• Glycerophosphate
• Lyophilization
• Hydrogel
• Stability

In the present study, lyophilization was attempted to improve the long-term storage of CS/GP thermogelling systems for biopharmaceutical applications. After lyophilization, CS/alpha,beta-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 alpha,beta-GP, inhibit the transfer of protons from CS to alpha,beta-GP, and then inhibit the aggregation of CS molecules during lyophilization. Comparison of the freshly prepared CS/alpha,beta-GP/salt solutions and the reconstituted solutions from lyophilizates showed that lyophilization clearly influenced the properties of reconstituted CS/alpha,beta-GP/salt solutions such as gelation time, viscosity, and pH. Furthermore, the reconstituted CS/alpha,beta-GP/CaCl2 solutions maintained thermogelling properties and formed hydrogels at 37 degrees C within approximately 5 min, but did not form hydrogels at 20 degrees C and 4 degrees C over 2 weeks. The model protein bovine serum albumin (BSA) was further incorporated into the CS/alpha,beta-GP/CaCl2 system. In vitro release experiments showed the sustained release of BSA from CS/alpha,beta-GP/CaCl2 hydrogels in a pH-sensitive manner, demonstrating that CS/alpha,beta-GP/CaCl2 may be useful as an in situ gel-forming system.

• 出版日期2016-9-10
• 单位河北师范大学