Aljaeid Bader Mubarak, Hosny Khaled Mohamed
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt.
Int J Nanomedicine. 2016 Jan 25;11:441-7. doi: 10.2147/IJN.S100625. eCollection 2016.
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.
咪康唑是一种广谱抗真菌药物，其水溶性较差（<1μg/mL）；因此，已有报道称其治疗效果有所降低。本研究的目的是制备并评估用于口服给药的载咪康唑固体脂质纳米粒（MN-SLNs），以找到一种创新方法来缓解与市售胶囊相关的缺点。
通过热均质/超声法制备MN-SLNs。测定了咪康唑在不同固体脂质中的溶解度。确定了工艺变量，如表面活性剂类型、均质和超声时间以及电荷诱导剂对粒径、zeta电位和包封率的影响。此外，还在兔子身上研究了体外药物释放、对白色念珠菌的抗真菌活性以及体内药代动力学。
由1.5%咪康唑、2% Precirol ATO5、2.5% Cremophor RH40、0.5% Lecinol和0.1%磷酸二鲸蜡酯组成的MN-SLN平均直径为23nm，包封率为90.2%。此外，与咪康唑胶囊相比，MN-SLNs制剂增强了抗真菌活性。体内药代动力学研究表明，生物利用度提高了2.5倍以上。
MN-SLN在治疗念珠菌病方面更有效，口服生物利用度提高，可能是咪康唑口服给药的有前途的载体。
