Design and Development of Nano Lipid Carrier Based Drug Delivery for Treatment of Skin Cancer

Skin cancer is a major global public health concern and includes melanoma, basal cell carcinoma, and squamous cell carcinoma [1]. Ultraviolet radiation exposure, oxidative stress, environmental pollutants, and genetic predisposition contribute significantly to skin carcinogenesis [2]. Conventional therapies such as chemotherapy, surgery, and radiotherapy are associated with adverse effects including systemic toxicity, poor selectivity, and recurrence [3]. Therefore, the development of novel targeted drug delivery systems is essential for improving therapeutic outcomes. Natural bioactive compounds have gained attention for cancer treatment because of their antioxidant, anti-inflammatory, and antiproliferative properties [4]. Curcumin, a polyphenolic compound obtained from Curcuma longa, has demonstrated significant anticancer activity through modulation of apoptosis, oxidative stress, angiogenesis, and inflammatory pathways [5]. However, poor aqueous solubility, low bioavailability, rapid metabolism, and limited skin penetration restrict its clinical application [6]. Nanostructured lipid carriers (NLCs) are advanced lipid-based nanosystems composed of solid and liquid lipids stabilized by surfactants [7]. NLCs improve drug stability, increase skin penetration, enhance drug loading, and provide controlled release properties [8]. Due to their nanoscale size and lipidic composition, NLCs facilitate targeted delivery to skin tissues while minimizing systemic exposure [9].

2. MATERIALS AND METHODS

2.1 MATERIALS

Curcumin was procured from a certified pharmaceutical supplier. Glyceryl monostearate and oleic acid were used as solid and liquid lipids respectively. Tween 80 and soy lecithin were used as surfactants. All chemicals and reagents used were of analytical grade.

2.2 Preparation of Nanostructured Lipid Carriers

Curcumin-loaded NLCs were prepared by hot homogenization followed by ultrasonication [10]. Solid lipid and liquid lipid were melted at 75°C. Curcumin was dissolved in the molten lipid phase. The aqueous surfactant phase was heated to the same temperature and added to the lipid phase under high-speed homogenization. The pre-emulsion obtained was ultrasonicated for 10 min and cooled to room temperature to form NLCs.

Composition of Optimized NLC Formulation

2.3 Characterization of NLCs

2.3.1 Particle Size and Polydispersity Index

Particle size and polydispersity index were determined using dynamic light scattering.

2.3.2 Zeta Potential

Zeta potential was measured to determine stability of the formulation.

2.3.3 Entrapment Efficiency

Entrapment efficiency was determined using centrifugation method.

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2.3.4 Morphological Analysis

Surface morphology of NLCs was examined using transmission electron microscopy (TEM).

2.3.5 Differential Scanning Calorimetry (DSC)

DSC analysis was performed to study thermal behavior and crystallinity of the formulation.

2.4 In Vitro Drug Release Study

Drug release study was carried out using dialysis membrane diffusion method in phosphate buffer (pH 7.4) at 37 ± 0.5°C. Samples were withdrawn at predetermined intervals and analyzed spectrophotometrically at 425 nm.

2.5 Skin Permeation Study

Ex vivo skin permeation studies were performed using Franz diffusion cells with excised rat skin.

2.6 Cell Culture and Cytotoxicity Assay

A375 human melanoma cell lines were cultured in DMEM supplemented with fetal bovine serum. Cytotoxicity of formulations was evaluated using MTT assay [11].

Percentage Cell Viability

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2.7 In Vivo Anticancer Study

Experimental skin cancer was induced in Swiss albino mice using 7,12-dimethylbenz[a]anthracene (DMBA) [12]. Animals were divided into four groups:

1. Normal control
2. Cancer control
3. Conventional curcumin gel-treated group
4. Curcumin-loaded NLC-treated group

Treatment was continued for six weeks.

2.8 Histopathological Examination

Skin tissues were fixed in formalin, embedded in paraffin, sectioned, stained with hematoxylin and eosin, and examined microscopically.

2.9 Statistical Analysis

Data were expressed as mean ± standard deviation. Statistical significance was analyzed using one-way ANOVA followed by Tukey’s test. Values of p < 0.05 were considered statistically significant.

3. RESULTS

3.1 Characterization of Nanostructured Lipid Carriers

The prepared NLCs showed good physicochemical characteristics.

The nanosized particles and narrow size distribution indicated formulation uniformity and stability.

3.2 Morphological Analysis

TEM analysis revealed spherical nanoparticles with smooth surfaces and uniform distribution.

3.3 Differential Scanning Calorimetry

DSC thermograms demonstrated reduced crystallinity of the lipid matrix, confirming successful incorporation of curcumin into the NLC system.

3.4 In Vitro Drug Release

The optimized NLC formulation exhibited sustained drug release over 24 h.

The sustained release profile indicated prolonged therapeutic action.

3.5 Ex Vivo Skin Permeation Study

The NLC formulation demonstrated significantly higher skin permeation compared with conventional curcumin gel.

Enhanced permeation was attributed to nanoscale size and lipid composition.

3.6 Cytotoxicity Study

The curcumin-loaded NLCs exhibited enhanced cytotoxicity against A375 melanoma cells.

Lower IC50 values indicated stronger anticancer activity of the NLC formulation.

3.7 In Vivo Anticancer Activity

The NLC-treated group demonstrated significant reduction in tumor volume and lesion severity.