Miconazole-loaded solid lipid nanoparticles: formulation and evaluation of a novel formula with high bioavailability and antifungal activity.
Miconazole-loaded solid lipid nanoparticles: formulation and evaluation of a novel formula with high bioavailability and antifungal activity.
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DOI：
10.2147/ijn.s100625
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发表时间：
2016
影响因子：
8
通讯作者：
Hosny KM
中科院分区：
文献类型：
--
作者：
Aljaeid BM;Hosny KM
咪康唑是一种广谱抗真菌药物，水溶性较差（<1 µg/mL）;因此，有报道称其疗效降低。本研究的目的是制定和评价口服给药的咪康唑固体脂质纳米粒（MN-SLN），以找到一种创新的方法来减轻与市售胶囊相关的缺点。通过热均质/超声处理制备MN-SLN。测定了咪康唑在不同固体脂质中的溶解度。的过程变量，如表面活性剂类型，均质化和超声处理时间，和电荷诱导剂上的粒径，zeta电位，和封装效率的影响进行了测定。此外，体外药物释放，对白色念珠菌的抗真菌活性，并在家兔体内的药代动力学进行了研究。MN-SLN由1.5%咪康唑、2% Precirol ATO 5、2.5% Cremophor RH 40、0.5% Lecinol和0.1% Dicetylphosphate组成，平均粒径为23 nm，包封率为90.2%。与咪康唑胶囊相比，MN-SLN制剂的抗真菌活性增强。体内药代动力学研究表明，生物利用度提高了>2.5倍。MN-SLN治疗念珠菌病的效果更好，口服生物利用度更高，有望成为咪康唑口服给药的理想载体。
Miconazole is a broad-spectrum antifungal drug that has poor aqueous solubility (<1 µg/mL); as a result, a reduction in its therapeutic efficacy has been reported. The aim of this study was to formulate and evaluate miconazole-loaded solid lipid nanoparticles (MN-SLNs) for oral administration to find an innovative way to alleviate the disadvantages associated with commercially available capsules. MN-SLNs were prepared by hot homogenization/ultrasonication. The solubility of miconazole in different solid lipids was measured. The effect of process variables, such as surfactant types, homogenization and ultrasonication times, and the charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release, antifungal activity against Candida albicans, and in vivo pharmacokinetics were studied in rabbits. The MN-SLN, consisting of 1.5% miconazole, 2% Precirol ATO5, 2.5% Cremophor RH40, 0.5% Lecinol, and 0.1% Dicetylphosphate, had an average diameter of 23 nm with a 90.2% entrapment efficiency. Furthermore, the formulation of MN-SLNs enhanced the antifungal activity compared with miconazole capsules. An in vivo pharmacokinetic study revealed that the bioavailability was enhanced by >2.5-fold. MN-SLN was more efficient in the treatment of candidiasis with enhanced oral bioavailability and could be a promising carrier for the oral delivery of miconazole.