a Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Modern University for Technology and Information , Cairo , Egypt.
b Department of Microbiology, Faculty of Medicine , Tanta University , Tanta , Egypt.
Drug Deliv. 2018 Nov;25(1):78-90. doi: 10.1080/10717544.2017.1413444.
Solid lipid nanoparticles (SLNs) are very potential formulations for topical delivery of antifungal drugs. Hence, the purpose of this research was to formulate the well-known antifungal agent Fluconazole (FLZ)-loaded SLNs topical gel to improve its efficiency for treatment of Pityriasis Versicolor (PV). FLZ-SLNs were prepared by modified high shear homogenization and ultrasonication method using different concentration of solid lipid (Compritol 888 ATO, Precirol ATO5) and surfactant (Cremophor RH40, Poloxamer 407). The physicochemical properties and the in vitro release study for all FLZ-SLNs were investigated. Furthermore, the optimized FLZ-SLN formula was incorporated into gel using Carpobol 934. A randomized controlled clinical trial (RCT) of potential batches was carried out on 30 well diagnosed PV patients comparing to market product Candistan 1% cream. Follow up was done for 4 weeks by clinical and KOH examinations. The results showed that FlZ-SLNs were almost spherical shape having colloidal sizes with no aggregation. The drug entrapment efficiency ranged from 55.49% to 83.04%. The zeta potential values lie between -21 and -33 mV presenting good stability. FLZ showed prolonged in vitro release from SLNs dispersion and its Carbapol gel following Higuchi order equation. Clinical studies registered significant improvement (p < .05) in therapeutic response (1.4-fold; healing%, 4-fold; complete eradication) in terms of clinical cure and mycological cure rate from PV against marketed cream. Findings of the study suggest that the developed FLZ loaded SLNs topical gels have superior significant fast therapeutic index in treatment of PV over commercially available Candistan cream.
固体脂质纳米粒（SLN）是一种很有前途的经皮递药制剂，适用于局部递运抗真菌药物。因此，本研究的目的是将广为人知的抗真菌药物氟康唑（FLZ）制成负载 SLN 的局部凝胶，以提高其治疗花斑癣（PV）的疗效。采用改良的高剪切匀化和超声法，使用不同浓度的固体脂质（Compritol 888 ATO、Precirol ATO5）和表面活性剂（Cremophor RH40、Poloxamer 407）制备 FLZ-SLN。研究了所有 FLZ-SLN 的理化性质和体外释放研究。此外，将优化的 FLZ-SLN 配方加入到使用 CarboPol 934 的凝胶中。对 30 例确诊的 PV 患者进行了潜在批次的随机对照临床试验（RCT），并与市售产品 Candistan 1%乳膏进行了比较。通过临床和 KOH 检查进行了 4 周的随访。结果表明，FLZ-SLN 呈近球形，具有胶体大小，无聚集。药物包封效率在 55.49%至 83.04%之间。Zeta 电位值在-21 至-33 mV 之间，呈现出良好的稳定性。FLZ 从 SLN 分散体及其 Carbapol 凝胶中表现出延长的体外释放，遵循 Higuchi 方程。临床研究表明，与市售乳膏相比，PV 的临床治愈率和真菌学治愈率均有显著提高（p<.05），治疗反应（愈合%提高 1.4 倍，完全消除率提高 4 倍）。研究结果表明，开发的 FLZ 负载 SLN 局部凝胶在治疗 PV 方面具有优越的快速治疗指数，优于市售的 Candistan 乳膏。
