载桂皮醛同轴静电纺丝纳米纤维膜的构建及性能评价

Preparation and performance evaluation of coaxially electrospun cinnamaldehyde nanofibers

目的用同轴静电纺丝技术构建桂皮醛纳米纤维膜并评价其药物缓释功能。方法用N,N-二甲基甲酰胺和二氯甲烷混合溶剂溶解聚己内酯和致孔剂聚乙二醇4000为壳层纺丝液,用无水乙醇溶解聚乙烯吡咯烷酮-K90和桂皮醛为芯层纺丝液;在电压为15 kV、接收距离为14 cm、芯层纺丝液流速为0.1 mm/min、不同壳层纺丝液流速(0.3、0.6、0.9 mm/min)条件下,用同轴静电纺丝工艺制备致孔剂含量及壳层厚度不同的壳-芯结构纳米纤维;用场发射扫描电镜、透射电镜表征,考察壳层厚度、致孔剂含量及投药量对桂皮醛包封率、载药量、稳定性及体外释放行为的影响,并对其体外释放行为进行数学模型拟合。结果载桂皮醛同轴纳米纤维表面光滑,纤维间无粘连,无串珠结构,直径为324~683 nm;呈现壳-芯结构,壳层随壳层纺丝液流速增大而增厚。壳层最厚的纤维中桂皮醛包封率最大(95.2%),芯层桂皮醛在壳层的保护下挥发受抑制,其稳定性最大值为82.5,远大于原料药(2.6);载桂皮醛的纳米纤维膜在PEG400-PBS缓冲液(pH 6.8)中24 h累积释放量为57.9%~89.1%,显示出良好的药物缓释效果,其释放速率与壳层厚度及载药量呈负相关,与致孔剂含量正相关。壳层不含致孔剂的载药纤维膜中桂皮醛的释放符合扩散机制,而壳层含有致孔剂的纤维膜中桂皮醛的释放遵循扩散与溶蚀相结合的双重机制。结论芯层含有易挥发药物桂皮醛的同轴纳米纤维膜不但增强了药物的包封率、载药量及稳定性,而且可实现药物缓释;据此可按释放要求构建桂皮醛同轴纳米纤维膜缓释给药体系。

Objective To construct cinnamaldehyde(TCA)nanofiber membrane capable of drug sustained release by coaxially electrospun technology. Methods Polycaprolactone(PCL)and polyethylene glycol(PEG)4000 were dissolved in dimethyl formamide(DMF)and dichloromethane(DCM)as shell spinning solutions while polyvinylpyrrolidone(PVP)-K90 and TCA were dissolved in absolute ethanol as core spinning solutions. The spinning process parameters were as follows:the applied voltage was at 15 kV,the collector distance was at 14 cm,the core solution flow rate was at 0.1 mm/min at different shell solution flow rates(0.3,0.6,and 0.9 mm/min). Shell-core structure nanofibers of different porous agent content and shell thickness were prepared by coaxial electrospining. The nanofibers were characterized with scanning electron microscopy and transmission electron microscopy. The entrapment efficiency,drug loading capacity,stability and the release behavior in vitro of TCA were investigated. The in vitro release behavior of TCA was fitted by a mathematical model. Results The coaxial nanofiber membrane had a uniform and smooth structure with the diameters ranging from 324 to 683 nm. The coaxial nanofibers had a clear shell-core structure,and the thickness in the shell increased with the velocity of the shell solutions. The entrapment efficiency of TCA was the highest(95.2%)in the nanofiber whose shell layer was the thickest. The volatilization of TCA in the core was inhibited under the protection of the shell layer,and its stability was stronger than that of TCA API. The nanofiber without any porous agent had the strongest stability(82.5). The cumulative release amount of nanofiber membrane loaded TCA was between 57.9%-89.1%,which showed good sustained release in PEG400-PBS buffer(pH 6.8),and the release rate was negatively correlated with shell thickness and drug-fed amount,but positively correlated with the porous agent content. The release of TCA from the drug loaded nanofibers without any porous agent in the shell conformed to the diffusion mechanism,while the release of TCA from the drug loaded nanofibers with a porous agent in the shell conformed to the dual mechanism of diffusion and dissolution. Conclusion The coaxial nanofiber membrane with volatile drug TCA in the core layer can not only enhance the entrapment efficiency,drug loading capacity and stability,but also ensure sustained release. A coaxial nanofiber sustained release drug delivery system can be designed according to the release requirements.