Design, optimization, and evaluation of nanostructured lipid carriers loaded prepared by microemulsion technique prepared topical gel for atopic dermatitis

Introduction

Topical drug delivery is advantageous for localized therapy, avoiding first-pass metabolism and systemic side effects. However, the stratum corneum's barrier limits penetration of poorly water-soluble drugs [1] . Curcumin has shown therapeutic potential in dermatology, including anti-inflammatory and wound-healing activities [2,3] , but its clinical utility is limited by physicochemical barriers [4] . Nanostructured lipid carriers (NLCs) combine solid and liquid lipids, creating an imperfect matrix that enhances drug loading and minimizes expulsion during storage [5] The microemulsion technique is a low-energy method that yields homogenous nanoparticles with narrow size distribution [6] . Soya lecithin, a natural phospholipid emulsifier, stabilizes lipid nanoparticles and is well-tolerated in topical systems [7] . Salicylic acid is a beta-hydroxy keratolytic agent used in dermatology to promote controlled desquamation of the stratum corneum, increasing skin permeation of co-administered actives [8][9][10][11] . Its integration into topical formulations may facilitate deeper delivery of encapsulated curcumin. This research develops, optimizes, and characterizes Cur-NLCs prepared by microemulsion, embeds the optimized dispersion in a salicylic acid gel, and discusses potential benefits for enhanced dermal delivery.

Materials and Methods

Materials

Curcumin was obtained from a pharmaceutical supplier. Stearic acid and coconut oil were used as lipid components. Soya lecithin served as an emulsifier. Carbopol 934 was used as a gel base. All chemicals were analytical grade.

Preformulation and compatibility

Solubility of curcumin in various lipids was assessed to identify suitable carriers. Compatibility of curcumin with selected lipids and soya lecithin was evaluated by mixing and thermal cycling [12] .

Preparation of curcumin-loaded NLCs

Cur-NLCs were prepared by the microemulsion technique. Stearic acid and coconut oil were melted at 70-75 °C; curcumin was dissolved in this lipid phase. Soya lecithin was added as a natural phospholipid emulsifier. The hot aqueous phase was added gradually to the lipid phase under stirring to form a thermodynamically stable microemulsion. The hot microemulsion was poured into cold water (2-4 °C) under gentle stirring, leading to rapid solidification of lipid droplets and formation of Cur-NLCs (6,13). The second-order polynomial model used was:

Experimental design and optimization

Statistical analysis was performed to assess significance [14,15] .

Characterization of Cur-NLCs 2.5.1 Particle size, PDI, and zeta potential

Dynamic light scattering measured particle size, PDI and zeta potential after appropriate dilution [16] .

Entrapment efficiency

Cur-NLCs were centrifuged; free drug in supernatant was quantified by UV spectrophotometry. %EE was calculated as: [17] .

Physical stability

Samples were stored at 4 °C and room temperature for 3 months; parameters were re-evaluated [18] .

Preparation of salicylic acid gel

A carbopol 934 gel was prepared with salicylic acid (2% w/w), neutralized with triethanolamine to achieve skincompatible pH. Optimized Cur-NLC dispersion was incorporated under gentle stirring. Increasing soya lecithin reduced particle size and PDI due to improved interfacial stabilization. Zeta values confirmed stability [16] . Entrapment enhanced with increased lipid and emulsifier due to improved curcumin solubilization within the lipid matrix [5,17] .

Results and Discussion

Formulation composition

Effect of variables on responses

Statistical analysis showed lipid and emulsifier concentrations significantly (p < 0.05) affected both particle size and%EE, as seen in the regression model coefficients.

The interaction term was significant for entrapment efficiency, indicating combined influence on drug-loaded structure formation [14,15] .

Physical stability

No significant changes in particle size or %EE were noted after 3 months, indicating stable NLCs suitable for topical formulation [18] .

Incorporation into salicylic acid gel

Salicylic acid promotes controlled desquamation and enhances permeation by loosening stratum corneum lipid structure [8][9][10][11] . Embedding Cur-NLCs into this gel base is expected to improve curcumin penetration while maintaining controlled release at the application site.

Conclusion

Curcumin-loaded NLCs prepared by microemulsion technique exhibited desirable nanoscale properties and high entrapment efficiency. Soya lecithin acted as an effective natural emulsifier, contributing to stability. Incorporation of Cur-NLCs into a salicylic acid gel presents a promising approach for enhanced dermal delivery for inflammatory and hyperkeratotic conditions. Future work will focus on invitro release and skin permeation studies.

Acknowledgement

The authors thank their institutional facility for support and resources.

Conflict of interest

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