Repurposing levocetirizine hydrochloride loaded into cationic ceramide/phospholipid composite (CCPCs) for management of alopecia: central composite design optimization, in- silico and in-vivo studies

Abstract

Levocetirizine hydrochloride (LVC) is an antihistaminic drug that is repurposed for the treatment of alopecia. This investigation is targeted for formulating LVC into cationic ceramide/phospholipid composite (CCPCs) for the management of alopecia. CCPCs were fabricated by ethanol-injection approach, through a central composite experiment. CCPCs were evaluated by inspecting their entrapment efficiency (EE%), polydispersity index (PDI), particle size (PS), and zeta potential (ZP). The optimum CCPCs were additionally studied by in-vitro , ex-vivo , in-silico , and in-vivo studies. The fabricated CCPCs had acceptable EE%, PS, PDI, and ZP values. The statistical optimization elected optimum CCPCs composed of 5 mg hyaluronic acid, 10 mg ceramide III, and 5 mg dimethyldidodecylammonium bromide employing phytantriol as a permeation enhancer. The optimum CCPCs had EE%, PS, PDI, and ZP of 88.36 ± 0.34%, 479.00 ± 50.34 nm, 0.377 ± 0.0035, and 20.20 ± 1.13 mV, respectively. The optimum CCPC maintained its stability for up to 90 days. It also viewed vesicles of tube shape via transmission electron microscope. The in-silico assessment resulted in better interaction and stability between LVC and vesicle components in water. The ex-vivo and in-vivo assessments showed satisfactory skin retention of LVC from optimum CCPCs. The histopathological assessment verified the safety of optimum CCPCs to be topically applied. Overall, the optimum CCPCs could be utilized as a potential system for the topical management of alopecia, with a prolonged period of activity, coupled with reduced LVC shortcomings.

Formulation optimization, in vitro and in vivo evaluation of niosomal nanocarriers for enhanced topical delivery of cetirizine

“…These findings support the results of the ex vivo permeation study, suggesting that niosomal vesicles, when applied to the skin, can partition across subcutaneous layer under the effect of the transcutaneous hydration gradient to form depots from which drugs can be released ( Peira et al, 2007 ). Similar findings were reported by Albash et al ( Albash et al, 2022 ) who emphasized the efficacy of cationic ceramide/phospholipid composite (CCPCs) in promoting better dermal deposition of levocetirizine hydrochloride from the optimum formula, compared to its solution.…”

“…Topical minoxidil and oral finasteride are considered the primary treatment options for androgenetic alopecia ( Adil and Godwin, 2017 , Suchonwanit et al, 2019 ). Nevertheless, despite their widespread application, their use is not without side effects ( Albash et al, 2022 ). Consequently, there is an urgent need for the development of novel therapies for the management of this distressing disorder.…”

“…The current treatment options focus mainly on reducing dihydrotestosterone and activating hair follicles via using 5-alpha reductase inhibitors such as finasteride or vasodilators such as minoxidil, respectively ( Adil and Godwin, 2017 , Suchonwanit et al, 2019 )). Nevertheless, despite their widespread application, their use is linked with the elicitation of undesirable adverse effects; finasteride use has been associated with the development of sexual side effects, whilst minoxidil application has been associated with the development of headache, hypotension, and irritant contact dermatitis ( Albash et al, 2022 ).…”

Exploring the Synergistic Effect of Bergamot Essential Oil with Spironolactone Loaded Nano-Phytosomes for Treatment of Acne Vulgaris: In Vitro Optimization, In Silico Studies, and Clinical Evaluation

“…After that, the supernatant was separated and collected to be examined at λ max 292 nm via a UV-Vis spectrophotometer (Shimadzu UV1650, Kyoto, Japan) [ 33 ]. The following equation was employed to calculate the EE% [ 32 , 34 ]:…”

Spanlastic-laden nanogel as a plausible platform for dermal delivery of bimatoprost with superior cutaneous deposition and hair regrowth efficiency in androgenic alopecia

“…The current pharmacologic therapies for alopecia target alleviating dihydrotestosterone and/or activating hair follicles via the use of oral 5-α reductase antagonists such as finasteride or topical vasodilators such as minoxidil ( Adil and Godwin, 2017 ; Suchonwanit et al, 2019 ). However, these treatment options elicit undesirable adverse effects; finasteride remarkably decreases dihydrotestosterone serum concentrations, triggering sexual side effects, whilst topical minoxidil commonly provokes pruritus and irritating contact dermatitis ( Albash et al, 2022 ). These elicited adverse effects exert a negative impact on patients' compliance and consequently compromise patients' adherence to therapy.…”