氟尿嘧啶温度敏感原位凝胶的制备及性能表征

Preparation and Characterization of Thermosensitive in Situ Hydrogel of 5-Fluorouracil

目的研究羧甲基壳聚糖(CMCS)/聚N-异丙基丙烯酰胺(PNIPAAm)原位凝胶的药物载体性能。方法以CMCS和N-异丙基丙烯酰胺(NIPAAm)为原料,通过交联/聚合反应制备具有温度敏感性的原位水凝胶,采用荧光显微镜、红外光谱等对凝胶结构进行表征,并考察不同配比的水凝胶的温度敏感性、溶胀动力学、退溶胀动力学以及反复收缩-溶胀动力学;以氟尿嘧啶(5-Fu)为模型药物,研究该凝胶对药物的控释性。结果在温度(20℃)低于体积相转变温度(VPTT)时,CMCS含量对水凝胶的溶胀比影响不大,但凝胶的溶胀比较大;在温度(37℃)高于VPTT时,凝胶的溶胀比随着CMCS含量的增加而增加,但溶胀比较小。引入CMCS后的原位凝胶的退溶胀响应速率比引入前快得多。例如PNI-C05凝胶在40 min时,凝胶失水率达到80%左右,而PNIPA凝胶失水率仅为40%左右。在药物释放方面,无论在碱性还是酸性环境中37℃下,CMCS含量越高,药物的释放率越大,通过调节凝胶中CMCS的含量可以控制药物的释放行为。结论 CMCS/PNIPAAm原位凝胶是一种潜在的口服药物的温敏控释载体。

OBJECTIVE To study the in situ hydrogels based on carboxymethyl chitosan（CMCS） and N-isopropylacrylamide（PNIPAAm） as the drug delivery systems.METHODS Thermo-sensitive in situ hydrogels based on CMCS and NIPAAm were prepared using the network polymerization technology.The interior morphology of the hydrogels was investigated by fluorescent microscope.The hydrogels were characterized by Fourier transform infrared（FT-IR）.The thermo-sensitivity,equilibrium swelling ratio,swelling deswelling and oscillatory shrinking-swelling dynamics of these hydrogels were investigated,,and 5-fluorouracil was selected as the model drug to examine their property of control and release from hydrogels.RESULTS The volume phase transition temperature（VPTT）was used as a reference temperature.When the temperature was at 20 ℃,which is below VPTT,the proportion of CMCS had minor effects on the equilibrium swelling ratio of the hydrogels.However,when the temperature was at 37 ℃,which is above VPTT,the equilibrium swelling ratio of the hydrogels increased by increasing the concentration of CMCS.Compared with the PNIPA hydrogel,the hydrogels synthesized with CMCS exhibited much faster response rate to temperature changes.In particular.PNI-C05 lost 80% water within 40 min,whereas the conventional hydrogel lost only about 40% water.Under both the acidic or alkaline conditions,the releasing ratio of 5-fluorouracil at 37 ℃ increased with higher CMCS content.The releasing rate of 5-fluorouracil was controlled by changing the CMCS content in the hydrogels.CONCLUSION Hydrogel based on carboxymethyl chitosan and PIPAAm is a potential thermosensitive in situ hydrogel for oral drug delivery.