Tazarotene-calcipotriol loaded Nanostructured lipid carrier enriched hydrogel: A novel dual drug synergistic approach towards Psoriasis management

Psoriasis with unclear etiology and pathogenesis is one of the most prevalent chronic skin diseases. It involves excessive keratinocytes cells hyperproliferation, abnormal vascular infiltration, and differentiation as its characteristic features. Patients need therapy on a periodic basis over a long period because of psoriasis recurrence. Thus, there is a requirement for target specific drug-delivery system to treat psoriasis effectively. Therefore, we proposed the preparation of Nanostructured Lipid Carriers (NLCs) containing Tazarotene (TZT) & Calcipotriol (CPT) by the solvent-melt-emulsification process for topical delivery. Our research work involves preparation, optimization by Box Behnken Design (BBD) and characterization of TZT CPT nano-lipid-carrier formulation and further incorporation into Carbopol 934 gel base to provide better adhesion on the skin for alleviating psoriatic lesions. The prepared NLC gel was further subjected to various in vitro and in vivo evaluations. The in-vivo characterization involved MTT assay, cellular uptake study, antioxidant, and lipid profile test, cytokine profile assessment, splenomegaly measurement, weight variation, etc. In-vitro parameters such as zeta-potential (mV), particle size (nm), and percentage entrapment efficiency of TZT-CPT-NLC formulation were found to be 149.340 +/- 0.340 nm, -13.14 +/- 0.20 mV & 91.24 +/- 7.30% respectively. SEM & TEM characterization demonstrated the spherical shape of both prepared TZT-NLC and TZT-CPT-NLC. The optimized TZT-CPT-NLC-based hydrogel showed 93.71 +/- 1.11% drug release during 72 h of study, following Higuchi-model with r2 = 0.960 value as the best fit drug release kinetic model. The prepared hydrogel-based formulations exhibited optimum viscosity, pH, and spreadability for easy topical application. No skin irritation was additionally detected for the developed hydrogel formulations. The newly developed TZT-CPT-loaded-NLC gel formulation showed improved antipsoriatic effectiveness as well as sustained release effect as compared with TZT-loaded-NLC gel, indicating that combination therapy may be a promising and viable option in topical management & treatment of psoriasis.

Automated summary

This study proposes the preparation of Nanostructured Lipid Carriers (NLCs) for the treatment of psoriasis and evaluates their effectiveness in vitro and in vivo. Results indicate that the TZT-CPT-NLC gel formulation exhibits good drug release and suitable chemical characteristics, suggesting that combination therapy may be a promising approach for the treatment of psoriasis.