Institute of Chemical and Engineering Sciences, A*STAR (Agency for Science, Technology and Research), 1 Pesek Road, Jurong Island, Singapore 627833, Singapore.
Nanotechnology. 2014 Mar 14;25(10):105102. doi: 10.1088/0957-4484/25/10/105102. Epub 2014 Feb 14.
This study focused on: (i) feasibility of the previously developed sucrose ester stabilized SLNs and NLCs to encapsulate different imidazole antifungal drugs and (ii) preparation and evaluation of topical gel formulations of those SLNs and NLCs. Three imidazole antifungal drugs; clotrimazole, ketoconazole and climbazole were selected for this study. The results suggested that size, size distribution and drug encapsulation efficiency depend on the drug molecule and type of nanoparticles (SLN/NLC). The drug release experiment always showed faster drug release from NLCs than SLNs when the same drug molecule was loaded in both nanoparticles. However, drug release rate from both SLNs and NLCs followed the order of climbazole > ketoconazole > clotrimazole. NLCs demonstrated better physicochemical stability than SLNs in the case of all drugs. The drug release rate from ketoconazole- and clotrimazole-loaded SLNs became faster after three months than a fresh formulation. There was no significant change in drug release rate from climbazole-loaded SLNs and all drug-loaded NLCs. Gel formulations of SLNs and NLCs were prepared using polycarbophil polymer. Continuous flow measurements demonstrated non-Newtonian flow with shear-thinning behavior and thixotropy. Oscillation measurements depicted viscoelasticity of the gel formulations. Similar to nanoparticle dispersion, drug release rate from SLN- and NLC-gel was in the order of climbazole > ketoconazole > clotrimazole. However, significantly slower drug release was noticed from all gel formulations than their nanoparticle counterparts. Unlike nanoparticle dispersions, no significant difference in drug release from gel formulations containing SLNs and NLCs was observed for each drug. This study concludes that gel formulation of imidazole drug-loaded SLNs and NLCs can be used for sustained/prolonged topical delivery of the drugs.
（i）先前开发的蔗糖酯稳定的 SLN 和 NLC 包封不同咪唑抗真菌药物的可行性，以及（ii）这些 SLN 和 NLC 的局部凝胶制剂的制备和评价。本研究选择了三种咪唑抗真菌药物：克霉唑、酮康唑和益康唑。结果表明，粒径、粒径分布和药物包封效率取决于药物分子和纳米颗粒（SLN/NLC）的类型。当相同的药物分子负载在两种纳米颗粒中时，药物释放实验总是显示出 NLC 比 SLN 更快地释放药物。然而，从 SLN 和 NLC 释放药物的速度均遵循益康唑>酮康唑>克霉唑的顺序。在所有药物的情况下，NLC 比 SLN 表现出更好的物理化学稳定性。酮康唑和克霉唑负载的 SLN 的药物释放率在三个月后比新鲜制剂更快。负载有克霉唑的 SLN 和所有负载药物的 NLC 的药物释放率没有明显变化。使用聚卡波非聚合物制备 SLN 和 NLC 的凝胶制剂。连续流动测量显示出具有剪切变稀行为和触变性的非牛顿流动。振荡测量描述了凝胶制剂的粘弹性。类似于纳米颗粒分散体，从 SLN 和 NLC 凝胶中释放药物的速度为益康唑>酮康唑>克霉唑。然而，从所有凝胶制剂中释放药物的速度明显比其纳米颗粒对应物慢。与纳米颗粒分散体不同，对于每种药物，在包含 SLN 和 NLC 的凝胶制剂中释放药物没有明显差异。本研究得出结论，负载有咪唑药物的 SLN 和 NLC 的凝胶制剂可用于药物的持续/延长局部递送。
