Delivery and Anti-Psoriatic Effect of Silibinin-Loaded Polymeric Micelles: An Experimental Study in the Psoriatic Skin Model

Abstract

Objective: Psoriasis is an inflamed skin disorder associated with activation of phosphorylation signals in keratinocytes which leads to proliferation. Phosphorylation signal inhibitors such as silibinin can inhibit cell proliferation. Unlike current psoriasis treatment approaches that are associated with dangerous side effects; natural components can introduce new trends in psoriasis treatment. The major problem in the topical treatment of psoriasis is drug localization through the psoriasis lesions. Methods: In this study, silibinin-loaded polymeric micelles prepared and characterized for drug loading and release and ex vivo permeation through psoriatic and normal mice skin. The optimized batch was used for the treatment of psoriasis lesions in the mice model. Results: The optimized batch demonstrated mean particle size 18.3±2.1 nm, entrapment efficiency 75.8±5.8%, and prolonged silibinin release. % Silibinin permeated through psoriatic skin after 48 treated by polymeric micelle and aqueous control was 80.35, and 92.6, respectively. Polymeric micelles increased silibinin localization in the psoriatic skin in comparison with control. In psoriatic skin after 7-10 days treatment by silibinin- loaded polymeric micelle there was no evidence of psoriasis and the histological evaluation showed no sign of psoriasis. Silibinin-loaded polymeric micelles reduced Psoriasis area index by more than 78% after 14 days. Conclusion: It seems that polymeric micelles increased the effectiveness of silibinin by drug localization into the psoriatic plaque. Topical STAT- 3inhibitors can be introduced as a new strategy in psoriasis treatment.

New Advances in Biomedical Application of Polymeric Micelles

“…Thus, the correct dose is delivered with lower skin deposition, decreasing the local side effects and augmenting the patient compliance and the efficacy of the treatment [139,140]. Over the last decade, numerous studies have been conducted with formulations containing PMs as drug vehicles for treating skin problems, with safety and efficacy benefits, even at a lower dose, as reviewed by Parra et al [139].and summarized in Table 3 [139,[141][142][143][144][145][146][147][148][149][150]. Over the last decade, numerous studies have been conducted with formulations containing PMs as drug vehicles for treating skin problems, with safety and efficacy benefits, even at a lower dose, as reviewed by Parra et al [139] and summarized in Table 3 [139,[141][142][143][144][145][146][147][148][149][150].…”

“…Enhancement in skin drug deposition [147] Resveratrol Pluronic ® P123 Pluronic ® F127 Decrease in the cytokine levels [148] Silibinin -Reduction of psoriasis index area [149] Enhancement in skin drug deposition [150] Terconazole Pluronic ® P123 Pluronic ® F127 Cremophor EL Higher permeation Higher skin deposition [142] The characteristics of PMs can be worked to alter their behavior and their efficacy. For example, increasing the length of the hydrophilic fragment, while maintaining the hydrophilic block's length can influence the micelle's size and reduce the CMC value.…”

Exploration of and insights into advanced topical nanocarrier systems for the treatment of psoriasis

“…The average particle size of the optimized samples was 18.3 ± 2.1 nm, the encapsulation efficiency was 75.8 ± 5.8%, and the release time of silybin was prolonged. Moreover, silibinin permeation through psoriatic skin after 48 h of treatment with polymeric micelles and the aqueous control was 80.35 and 92.6, respectively ( 53 ). These micelles have been designed for targeted drug delivery because of their easy structural deformation under the influence of pH, temperature, or reduction-oxidation reactions in vivo .…”

Polymeric Micelles: A Promising Pathway for Dermal Drug Delivery

“…Silibinin (SL) is a flavonolignan found in milk thistle, Silybum marianum , and also a silymarin component and possesses hepatoprotective action, along with antioxidant and antineoplastic activity, and can act as a phosphorylation signal inhibitor [ 49 ]. As psoriasis is often related with the activation of phosphorylation signals in keratocytes, SL efficacy as an alternative to the conventional treatment was studied by Chavoshy et al [ 44 ]. A series of SL-loaded PM were prepared, and permeation through skin in psoriatic and non-psoriatic mice was evaluated.…”