L-肉毒碱复合聚乙二醇-b-聚ε-己内酯纤维的W/O乳液电纺制备及表征

Preparation and characterization of L-carnitine/polyethylene-b-polyε-caprolactone fibers electrospun from W/O emulsion

目的用油包水乳液静电纺丝法制备并评价包载有L-肉毒碱的聚乙二醇-b-聚ε-己内酯电纺纤维毡。方法将L-肉毒碱溶解在水中为水相,将聚乙二醇与聚ε-己内酯嵌段质量比为1∶75的共聚物和1∶5的共聚物溶解在二氯甲烷中为油相,混合并超声形成W/O乳液后静电纺丝得纤维毡。扫描电子显微镜观察纤维毡形态并用图形软件进行纤维直径分布分析,广角X-射线衍射扫描观察纤维表面结晶状态,差示扫描量热评价药物在高分子材料中的结合状态,高效液相色谱测定药物体外释放结果。结果随着油相中聚乙二醇与聚酯嵌段质量比为1∶75和1∶5两种共聚物的含量比例由高到低,纤维形状由直径较均匀的纤维向直径不均匀的纤维转变,最终形成连接珠形态,平均直径和最大直径逐渐增高。所得纤维表面光滑无结晶态物质析出,X-射线衍射没有发现L-肉毒碱特征峰出现。差示扫描量热结果显示L-肉毒碱的加入使纤维的玻璃化温度降低。随着平均直径的增高,L-肉毒碱释放速率逐渐减慢。结论采用较高相对分子质量聚酯作为成纤材料,相对分子质量较低且聚乙二醇嵌段比例较高的嵌段聚酯为乳化剂,可制得载L-肉毒碱纤维毡作为局部药物控制释放系统。

Objective To prepare and evaluate L-carnitine entrapped polyethylene glycol blocked polyε-cap-rolactone electrospun fibrous mats by aqueous in oil emulsion method. Methods L-camitine was dissolved in water which used as inner aqueous phase, and polyethylene glycol blocked polyε-caProlactone with 1：75 and 1： 5 of polyethylene and polyε-caprolactone block ratio was dissolved in dichloromethane which was used as outer oil phase. These two phases were mixed and ultra-sonicated to form W/O emulsion before electrospin-ning to obtain fibrous mats which were observed morphologically by scanning electron microscope. Fiber surface crystalline state was detected by wide angle X-ray diffraction. L-carnitine-polymer material composi-tion state was evaluated by differential scanning calorimetry. High performance liquid chromatography was used to determine drug in vitro release. Results Surfaces of fibers were smooth and as the ratio of polyethy-lene glycol blocked polyester with blocks of 1 ： 75 and 1： 5 in the oil phase changed, shape of fibers changed from homogeneous-diameter fiber to unhomogeneous ones, and at last to the morphology of beads linked by fibers. Wide angle X-ray diffraction indicated no character peak of L-carnitine. Differential scanning calorim-etry presented that addition of L-carnitine lowered the glass temperature of the fibrous mats. As the average diameter became higher,release speed of L-carnitine became lower. Conclusions By using respectively high and low molecule weight polyester as fiber-formation material and emulsifier in which the later contains high ratio of polyethylene glycol block,L-camitine fibrous mats can be prepared for local drug delivery system.