同时缓释骨形态发生蛋白和氯己定的功能性壳聚糖温敏凝胶的制备

Preparation of Functional Chitosan Thermosensitive Hydrogel for Slow Release both rhBMP-2 and Chlorhexidine

摘要:

壳聚糖温敏凝胶是一种新型的可注射、在体固化的载体材料，该材料在室温条件下呈生理中性的溶液状态，在37℃左右可由溶液转变成水凝胶。该水凝胶对大分子药物具有良好的缓释效能，但对小分子药物缓释效能极差。 为制备同时缓释生长因子重组人骨形态发生蛋白- 2 (recombined human bone morphogenetic protein - 2, rhBMP-2)和抗菌药物氯己定的功能性壳聚糖温敏凝胶，将小分子药物氯己定先与β-环糊精制备成包结物，再将rhBMP-2与β-环糊精/氯己定包结物共混于壳聚糖温敏凝胶中，通过HAAKE粘度测量仪,对比加入目标药物前后系统的流变学性质，并且分别通过高效液相(high performance liquid chromatography，HPLC)和酶联免疫吸附(enzyme-linked immunosorbent assay, ELISA)方法测量目标药物的体外释放性质，温敏凝胶系统的流变学性质几乎未受加入药物的影响。而氯己定从凝胶系统中释放的速度大大减慢，药物持续释放可保持1月以上。同时，rhBMP-2也获得较好的缓释效果。 通过先行环糊精包结共混的方法，成功制备同时缓释rhBMP-2和氯己定的功能性温敏凝胶。

Abstract:

The chitosan thermosensitive hydrogel is liquid at room temperature but gels rapidly when heated to body temperature. This hydrogel are wildly used for cell encapsulation, drug delivery or tissue-engineered scaffolds. The system can sustain the release of macromolecules over a period of several hours to a few days. However, with low-molecular-weight compounds, the release is generally completed within 24 h. To prepare a functional chitosan thermosensitive hydrogel for slow release both broad-spectrum antibiotic chlorhexidine and growth factor recombined human bone morphogenetic protein\|2 (rhBMP-2),The β-cyclodextrin was used to prepare an inclusion complex with chlorhexidine, and then the latter was incorporated into the chitosan thermosensitive hydrogel system. Simultaneously, rhBMP-2 was added into thecoelastic properties of system with or without objective factors. And the in vitro release kinetics of chlorhexidine and rhBMP-2 was investigated by HPLC (high performance liquid chromatography) and ELISA (enzyme-linked immunosorbent assay) respectively.The results showed that the addition of chlorhexidine/β-cyclodextrin inclusion complex to the thermosensitive solution did not change the gelling behavior of the thermosensitive system. Further, the in vitro release profiles demonstrated that the release rate of chlorhexidine and rhBMP-2 from hydrogel became slower, controlled delivery over at least 1 month.By first preparing chlorhexidine/β-cyclodextrin inclusion complex, and then mixing the IC and rhBMP-2 into the chitosan thermosensitive hydrogel, a functional chitosan thermosensitive hydrogel system with ability of slow release both rhBMP-2 and chlorhexidine is successfully made.