Assessment of the therapeutic efficacy of rutin-loaded PLGA nanocapsule-based gel against imiquimod-induced psoriasis model using box-behnken design for optimization

Psoriasis is a chronic, immune-mediated inflammatory skin disorder characterized by epidermal hyperplasia, hyperkeratosis, and notable infiltration of inflammatory cells. This study aims to evaluate the potential of a rutin (RT)-loaded poly(lactic-co-glycolic acid) (PLGA) nanocapsule-based gel as a topical treatment for psoriasis. Rutin-loaded poly(lactic-co-glycolic acid) (PLGA) nanocapsules (RT-NCs) were prepared using the interfacial polymer deposition technique. Various factors were studied by Box-Behnken design to propose an optimized nanocapsule formulation with desirable characteristics before incorporation into different Carbopol 940 bases. The selected RT nanocapsule gel (RT-NG) formulation was subjected to physicochemical characterization, compatibility, in vitro drug release, and ex vivo skin permeation studies. In vivo studies were also performed using an Imiquimod (IMQ)-induced psoriasis rat model. Results revealed that the RT-NCs containing 30 mg of RT, 83.5 mg of PLGA, and 4 % w/v polyvinyl alcohol (PVA) were optimal, with the highest desirability value of 0.601. The RT-NG containing 1 % w/w Carbopol 940 with a (2:1) gel to RT-NC ratio (RT-NG4) was chosen for topical application. An ex vivo skin permeation study demonstrated that the use of PLGA-NCs enhanced RT penetration into the epidermis. In vivo experiments showed that RT-NG4 treatment effectively alleviated IMQ-induced psoriasis-like skin symptoms, yielding the lowest total Psoriasis Area and Severity Index (PASI) scores (3.67 ± 0.58) compared to pure RT gel (8.00 ± 1.00). The Spleen/Body Weight (SBW) ratio was also reduced in the RT-NG4 group compared to pure RT gel. Moreover, enzyme-linked immunosorbent assay (ELISA) results revealed that RT-NG4 treatment reduced the levels of TNF-α, IFN-ɣ, and IL-6 and inhibited antioxidative stress compared to pure RT gel. In conclusion, the novel RT-NG formulation demonstrated promising potential as an effective topical treatment for psoriasis, leveraging the therapeutic benefits of a natural product.