Tazarotene-calcipotriol loaded Nanostructured lipid carrier enriched hydrogel: A novel dual drug synergistic anti-psoriatic 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 of time because of psoriasis recurrence. Thus, there is a requirement for target specific drug-delivery system for numerous medications 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 Tazarotene (TZT)Calcipotriol (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 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 anti-psoriatic 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.

Materials

Calcipotriol & Tazarotene both were purchased from Shaanxi Owens Industry Co., Ltd. China; Miglyol 812 N and Pericerol-ATO-5 was kind gifts from IOI Oleo GmbH production Germany & Gattefosse SAS, France; Pluronic-F-188 obtained by research lab fine chem industries; Chloroform, polypropylene-ethyl-glycol, methanol-solvent, Carbopol 934 grade, Triethonalamine,HaCaT cell line, Dulbecco’s Modified Eagle Medium, fetal bovine serum, antibiotic solution, MTT dye and Tryptan

Sunita Thakur, Md Meraj Anjum, Shweta Jaiswal, Anurag Kumar Gautam, Paruvathanahalli Siddalingam Rajinikanth,
Tazarotene-calcipotriol loaded Nanostructured lipid carrier enriched hydrogel: A novel dual drug synergistic anti-psoriatic approach towards Psoriasis management, Journal of Drug Delivery Science and Technology, 2023, 104944, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2023.104944.