Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Int J Pharm. 2011 Aug 30;415(1-2):119-28. doi: 10.1016/j.ijpharm.2011.05.060. Epub 2011 May 30.
The present work was carried out to design a practical, controlled-release transdermal system for selegiline using thermosensitive hydrogels. The copolymers of alginate and Pluronic F127 (PF127) were used to design thermogels by either physical blending (A+P) or chemical grafting (AP). The thermogels were characterized in terms of the sol-gel temperature, scanning electron microscopy (SEM), degradation ratio, and skin permeation behavior. The chemical grafting of alginate to PF127 could delay the sol-gel temperature from 24.1 to 30.4°C, which is near the temperature of the skin surface. The gelling temperature of the physical mixture of alginate and PF127 (A+P) did not significantly differ. The porosity of the A+P structure was greater compared to that of the AP structure. AP thermogels were regularly degraded, with 60% of the gel matrix remaining after a 48-h incubation. PF127 and A+P hydrogels showed almost no degradation. The results of skin permeation across porcine skin and nude mouse skin suggested that the thermogels could produce sustained selegiline release, with AP showing the most-sustained permeation. AP hydrogels exhibited linear permeation properties for the transdermal delivery of selegiline. Inter-subject variations in skin permeation were reduced by incorporation of the thermogel. Such a thermosensitive hydrogel can be advantageous as a topical therapeutic formulation for selegiline.
本工作旨在设计一种使用温敏水凝胶的实用型、盐酸司来吉兰控释透皮系统。采用海藻酸钠和泊洛沙姆 F127(PF127)共聚物通过物理共混(A+P)或化学接枝(AP)来设计温敏水凝胶。从溶胶-凝胶温度、扫描电子显微镜(SEM)、降解率和皮肤渗透行为等方面对温敏水凝胶进行了表征。海藻酸钠化学接枝到 PF127 可将溶胶-凝胶温度从 24.1°C延迟至 30.4°C,接近皮肤表面温度。海藻酸钠和 PF127 的物理混合物(A+P)的胶凝温度没有显著差异。A+P 结构的孔隙率大于 AP 结构。AP 温敏水凝胶有规则的降解,孵育 48 小时后,凝胶基质仍有 60%残留。PF127 和 A+P 水凝胶几乎没有降解。猪皮和裸鼠皮的皮肤渗透结果表明,温敏水凝胶可产生持续的盐酸司来吉兰释放,AP 显示出最持续的渗透。AP 水凝胶对盐酸司来吉兰的透皮传递表现出线性渗透特性。温敏水凝胶的加入降低了皮肤渗透的个体间差异。这种温敏水凝胶作为盐酸司来吉兰的局部治疗制剂具有优势。