Volume : 13, Issue : 07, July – 2026
Title:
DEVELOPMENT AND CHARACTERIZATION OF FLUOROURACIL-LOADED SOLID LIPID NANOPARTICLE GEL FOR ENHANCED TOPICAL DELIVERY IN SKIN CANCER
Authors :
J. Krishna Prasad*, Dr. Manish Kumar Mishra, Dr. Dalu Damayanthi
Abstract :
Skin cancer is a major dermatological challenge, and topical chemotherapy often remains limited by inadequate skin penetration, poor retention within viable epidermis, and nonselective drug distribution. Solid lipid nanoparticles (SLNs) provide a promising platform for improving local skin targeting because they combine nanoscale size, lipid compatibility, occlusive behavior, and the potential for controlled drug deposition within epidermal and dermal layers. The present work focused on the development, characterization, and biological evaluation of fluorouracil-loaded SLNs for topical treatment of skin cancer. Fluorouracil was selected because of its established clinical role in topical management of premalignant and malignant skin lesions and because prior studies have shown its efficacy against UVB-associated skin damage and tumorigenesis (Khan et al., 2020; Narayana Pillai et al., 2020; Roy et al., 2018).
Preformulation studies included physicochemical characterization, partition coefficient estimation, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and analytical method development for drug estimation. The study reported a highly linear calibration curve for fluorouracil at 260 nm, with R2=0.9983, supporting reliable analytical quantification during formulation studies. Fluorouracil-loaded SLNs were then prepared and characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, drug loading, morphology, crystallinity, and thermal behavior. The optimized formulation showed a mean particle size of 220 ± 0.9 nm, PDI of 0.419 ± 0.035, zeta potential of −18.5±0.3 mV, entrapment efficiency of 88.3 ± 2.3%, and drug loading of 1.9 ± 0.3%.
The optimized SLN dispersion was incorporated into a Carbopol 934 gel and evaluated for pH, viscosity, spreadability, extrudability, homogeneity, occlusive behavior, and drug content. The final gel showed a pH of 6.88 ± 0.21, drug content of
99.68 ± 0.89%, viscosity of 5.28 Pa·s, spreadability of 5.24 ± 0.24 cm, and extrudability of 53.35 g/cm2^22, indicating acceptable suitability for topical use. Dermatokinetic studies showed markedly enhanced deposition of fluorouracil from the SLN gel compared with conventional gel. In epidermis, Cskin max increased from 89.7 ± 9.5 to 205.9 ± 13.8 μg/cm2, while in dermis it increased from 96.8 ± 7.8 to 220.8 ± 8.5 μg/cm2. Confocal laser scanning microscopy demonstrated that fluorescence from conventional gel became negligible after 45 μ\μm, whereas SLN gel fluorescence extended to about 60 μ\muμm, indicating deeper deposition.
Mechanistic studies using FTIR and DSC of treated skin suggested lipid disruption, lipid fluidization, and keratin alteration as contributors to enhanced skin permeation. Ex vivo anti-cell proliferation data showed concentration-dependent cytotoxicity of the fluorouracil SLN gel, and in vivo studies indicated absence of visible skin irritation and reduced inflammatory mediators such as IL-1α and TNF-α in tumor-bearing skin compared with placebo and conventional gel groups. Taken together, these findings indicate that fluorouracil-loaded SLN gel is a promising topical nanocarrier system for improving local drug delivery and therapeutic performance in skin cancer.
Keywords: fluorouracil; solid lipid nanoparticles; topical gel; skin cancer; Dermatokinetic; epidermal targeting
Cite This Article:
Please cite this article in press J. Krishna Prasad et al., Development And Characterization Of Fluorouracil-Loaded Solid Lipid Nanoparticle Gel For Enhanced Topical Delivery In Skin Cancer, Indo Am. J. P. Sci, 2026; 13(07).
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