葛根素参与的可注射钙离子敏感凝胶构建和性质研究

Construction and proprieties of a puerarin-interact, injectable and Ca2+ responsive gel

关键词:  葛根素  海藻酸钙  可注射凝胶  离子敏感凝胶  骨关节炎

Key words:  puerarin  calcium alginate  injectable gel  ion responsive gel  osteoarthritis

摘要:

[目的]构建一种葛根素（Pu）参与的海藻酸钙水凝胶，具有可注射性和钙离子敏感性，可用于控释药物或负载间充质干细胞，用于骨关节炎治疗。[方法]以海藻酸钠（SA）、氯化钙（CaCl₂）和Pu为原料制备不同处方凝胶，黏度计实验考察处方原料对凝胶黏度的影响，通过流变学方法筛选最佳处方，并考察Pu对凝胶强度的影响，观察冻干凝胶的微观结构，通过溶胀实验、体外降解实验和药物释放实验考察凝胶溶胀率、体外稳定性和药物缓释性能。[结果]通过物理搅拌得到均一透明凝胶，处方中原料对凝胶强度影响大小顺序为CaCl₂ > SA > Pu，筛选最佳处方为0.2% Pu+0.6% SA+6 mmol/L CaCl₂，扫描电微镜下凝胶呈现三维网孔结构，表征实验表明Pu对凝胶强度有促进作用，Pu使凝胶溶胀率由75倍减小至45倍，体外初始降解时间由12 d增加至24 d，该凝胶对粉防己碱具有良好的缓释作用。[结论] Pu参与海藻酸钙凝胶构建，增加胶凝强度并改善凝胶溶胀和体外降解性质，该凝胶强度适宜并呈三维网孔结构，对粉防己碱有缓释作用，是良好的可注射型药物或干细胞载体用于骨关节炎的治疗。

Abstract:

[Objective] A puerarin-interact calcium alginate scaffold gel was build for the treatment of osteoarthritis. The gel has the properties of injectable, Ca²⁺-responsive, controlled release of drugs as well as the Mesenchymal Stem Cells (MSCs) support characteristic.[Methods] Sodium alginate (SA), CaCl₂ and puerarin (Pu) were used as the raw materials for the preparation of gels. Explore the effects of Pu on viscosity by the Viscometer. The best formulation was chosen by the method of Rheology and the effects of Pu on gelatinization were explored. The microstructure of lyophilized gels was observed. Their properties of welling ratio, vitro degradation and drug release were studied.[Results] The homogeneous and transparent gels were obtained by physical stirring. The effect of raw materials on the gel strength was in order of CaCl₂ > SA > Pu and the best formulation was 0.2% Pu+0.6% SA+6 mmol/L CaCl₂, Their 3D mesh structures were showed by the SEM. The characterization experiments suggest that Pu has promoting effects on gel strength. Compared with the Ca²⁺-alginate gel, the swelling ratio of Pu-calcium alginate gel decrease from 75 to 45 times and the initial degradation time prolonged from 12 d to 24 d. The gel showed sustained-release property on alkaloid Tetrandrine.[Conclusion] Pu was involved in the construction of calcium alginate gel, which increased the gel strength and improved the properties of swelling and vitro degradation. The gel had better strength and showed 3D mesh structure. It had sustained-release property on alkaloid Tetrandrine. The Pu-calcium alginate gel was expected to be the injectable scaffolds of drugs or MSCs for the treatment of osteoarthritis.