Faculty of Pharmacy, University of Montreal, C.P. 6128 Succ. Centre-ville, Montreal, Quebec H3C 3J7, Canada.
Pharm Res. 2004 Mar;21(3):454-7. doi: 10.1023/B:PHAM.0000019299.01265.05.
To characterize novel pharmaceutical organogels based on the self-assembly of L-alanine derivatives in hydrophobic vehicles.
The gelation properties of N-lauroyl-L-alanine (LA) and N-lauroyl-L-alanine methyl ester (LAM) were investigated in the presence of various solvents. Gel-sol and sol-gel transitions were evaluated by the inverse flow method, and gelation kinetics were determined by turbidimetry. The in vitro release kinetics of labeled dextran physically dispersed in the oil-based organogel was assessed in phosphate-buffered saline. In situ formation of the implants was evaluated in rats by subcutaneously injecting a solution containing LAM, an oil, and a water-diffusible inhibitor of self-assembly (ethanol).
The LAM-containing formulations showed a hysteretic gelling behavior with transition temperatures between 10 and 55 degrees C. Gelation kinetics exhibited a lag time of 10 and 30 min at 25 and 37 degrees C, respectively. In vitro, fluorescein isothiocyanate-dextran was released from the gel in a sustained manner with less than 6% released after 20 days. The addition of ethanol to the LAM/oil mixture inhibited gelation and allowed subcutaneous injection of the solution at room temperature. After injection, ethanol diffusion led to the formation of a solid implant.
Low-molecular weight self-assembling organogelators may allow the preparation of novel in situ-forming hydrophobic implants.
以疏水性载体中 L-丙氨酸衍生物的自组装为特征，研究新型药物有机凝胶。
研究了 N-月桂酰-L-丙氨酸（LA）和 N-月桂酰-L-丙氨酸甲酯（LAM）在不同溶剂中的凝胶特性。采用逆流法评价凝胶-溶胶和溶胶-凝胶转变，用浊度法测定凝胶化动力学。通过测定物理分散在油基有机凝胶中的标记葡聚糖的体外释放动力学来评估其释放动力学。通过皮下注射含有 LAM、油和自组装抑制剂（乙醇）的水溶液，在大鼠体内评价植入物的原位形成。
含 LAM 的制剂表现出滞后凝胶化行为，转变温度在 10 至 55°C 之间。凝胶化动力学在 25 和 37°C 时分别具有 10 和 30min 的滞后时间。在体外，荧光素异硫氰酸酯-葡聚糖以持续的方式从凝胶中释放，20 天后释放量小于 6%。在 LAM/油混合物中加入乙醇可以抑制凝胶化，并允许在室温下注射溶液。注射后，乙醇扩散导致形成固体植入物。
低分子量自组装有机凝胶剂可用于制备新型原位形成的疏水性植入物。
