Development of Turmeric Oil-based 5-Fluorouracil Loaded Lipid Nanogel for Improved Dermatokinetic and Drug Deposition for Skin Cancer
- PMID: 41320242
- DOI: 10.5650/jos.ess25076
Development of Turmeric Oil-based 5-Fluorouracil Loaded Lipid Nanogel for Improved Dermatokinetic and Drug Deposition for Skin Cancer
Abstract
Hydrophilicity and side effects are the major problems in the effective and safe use of 5-fluorouracil (5FL) for skin cancer. Lipid-based nanocarriers, especially nanostructured lipid carriers (NLC), show specific advantages of high drug loading and low drug leakage for successful delivery of 5FL. Therefore, a lipid-nanogel system of 5FL-loaded NLC (5FL-LNG) for topical delivery was aimed at in the present study. For NLC development, a mixture of turmeric oil and labrasol (70:30) was determined as oil, and then solid lipid (tefose 1500) and surfactant (Tween 80) were selected. Central composite design was used for formulation optimization. Design suggested a formulation prepared with 1.5% binary mixture, 6% surfactant, and 8 min of sonication time for the optimized 5FL-NLC. Optimized 5FL-NLC had particle size, zeta potential, entrapment efficiency, and transmittance values of 223.47±2.42 nm, -14.90±0.95 mV, 78.81±1.63%, and 94.79±0.58%, respectively. The DSC revealed homogeneous and amorphous nature of 5FL-NLC. 5FL-LNG formulation was prepared with 1% w/w Carbopol® 934 and compared with conventional Carbopol® 934 gel of 5FL. Spreadability and extrudability were better for 5FL-LNG and were further confirmed by texture analysis. In vitro release and skin permeation (both in vitro and ex vivo) of 5FL was better for 5FL-LNG compared to the conventional gel. Dermatokinetic data showed that Cskin-max and AUC0-8h values were significantly higher for 5FL-LNG. Confocal laser scanning microscopy confirmed noticeable betterment of 5FL delivery to skin epidermis and dermis from 5FL-LNG compared to conventional gel. Overall, developed 5FL-LNG formulation demonstrated its significant results for effective topical application and, therefore, could be subjected to further pre-clinical and clinical studies.
Keywords: 5-fluorouracil; dermatokinetics; lipid nanogel; melt-ultrasonication; nanostructured lipid carriers.
