Low molecular weight protamine-corticosteroid conjugate for topical treatment of psoriasis: A hypothesis

Abstract

Psoriasis is a chronic, autoimmune inflammatory skin disease caused by disturbed keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis. In addition to long-term damages to skin, psoriasis also leads to numerous comorbidities, including psoriatic arthritis (PsA), cardiovascular and psychiatric complications, which seriously burdens the physical and psychological health of sufferers. Fluocinolone acetonide (FA) is a synthetic fluorine-containing potent corticosteroid, which can inhibit fibroblast proliferation, reduce skin inflammation and relieve itching. However, topical administration of FA for psoriasis treatment is restricted by its dose-dependent side effects mostly related to the high doses required or increased use frequency of FA owing to the chronic nature of psoriasis and the deprivations of FA. Cell penetration peptides (CPPs) based peptide–drug conjugates (PDCs) provide several benefits associated with delivery carriers, such as facilitating drugs' skin penetration, enhancing their cellular uptake, and improving their therapeutic efficacy. Low molecular weight protamine (LMWP) is an effective CPP from protamine enzymatic digestion. It holds an effective skin permeation capacity to act as a skin enhancer peptide. In this study, we hypothesize the construction of a reduction responsive LMWP-based FA conjugate nanostructure (LMWP-FA) for improving the therapeutic effects of FA in psoriasis. LMWP conjugation of FA would allow the enhanced skin permeation and promoted uptake by keratinocytes. The nanostructure and on-demand release under the intracellular reducing environment of LMWP-FA could locate FA in the psoriatic lesions to exert anti-inflammatory effects preventing its entry into the circulatory system. Taken together, the present hypothesis proposed a novel idea for FA to increase therapeutic efficiency and avoid side effects in the treatment of psoriasis.