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

详细信息    查看全文

• 作者：Guanghao Wu¹ ; Yuan Yuan¹ ; Jintian He ; ^{576477418@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Ying Li ; Xiaojing Dai ; Baohua Zhao ; ^{zhaobaohua86178@sohu.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Chitosan ; Glycerophosphate ; Lyophilization ; Hydrogel ; Stability
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：10 September 2016
• 年：2016
• 卷：511
• 期：1
• 页码：560-569
• 全文大小：1795 K

文摘

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 5 min, 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.