治疗耳聋的地塞米松原位凝胶给药系统的研究

 目的探索温度敏感原位凝胶作为内耳局部给药载体的可行性,为其治疗耳聋提供依据。方法以泊洛沙姆407为基质制备地塞米松磷酸钠(DSP)温度敏感原位凝胶,测定其低临界溶液温度(LCST)。建立DSP和地塞米松(Dex)HPLC测定方法；考察凝胶中药物的稳定性；采用扩散池方法评价其体外释放行为；与溶液剂相比较,研究鼓室注射载药原位凝胶后耳蜗外淋巴液中药动学规律。结果制得的DSP温度敏感原位凝胶的LCST为26.5℃,制剂较稳定,体外释放遵循Higuchi方程。鼓室注射DSP原位凝胶,药物在内耳组织的局部生物利用度显著提高,AUC是静脉注射DSP溶液的492.8倍；而且其缓释特征明显,同鼓室注射DSP溶液相比,MRT增加了近5倍。结论温度敏感原位凝胶传递系统可望成为一种新型的内耳局部给药系统,值得进一步开发研究。

Study on Dexamethasone Thermosensistivie in Situ Gel for Treating Deafness

OBJECTIVE To investigate the feasibility of deliverying drug regionally to the inner ear using dexamethasome in situ gel,and provide scientific information for treating deafness.METHODS DSP(dexamethasone sodium phosphate)-loaded thermosensitive in situ gel was prepared by using poloxamer 407 as material.A HPLC method was established for the determination of DSP and dexamethasone(Dex). The pharmaceutical properties of DSP gel,such as lower critical solution temperature(LCST),DSP stability and release in vitro,were estimated.The pharmacokineties of DSP-loaded gel and solution were studied after an intratympanic or intravenous administration by determining the concentration of Dex in perilymph.RESULTS DSP-loaded gel had good stability,and its LCST was 26.5℃.The in vitro release kinet-ics was well characterized by Higuchi equation.The pharmacokinetic results showed that the perilymph AUC of intratympanic injection(it) DSP-loaded gel was 492.8-fold higher than that of iv DSP solution.Moreover,DSP-loaded gel following it extended the MRT by 5 times or compared with the solution.CONCLUSION Thermnsensitive in situ gel is a promising inner ear-oriented drug delivery system.