Pivotal role of Acitretin nanovesicular gel for effective treatment of psoriasis: ex vivo–in vivo evaluation study

Abstract

The goal of the current study was to explore the potential benefits of Acitretin (Act) nanovesicular gel as a prospective antipsoriatic topical delivery system counteracting the drug challenges in terms of its extremely low aqueous solubility, instability, skin irritation, and serious systemic adverse effects. Act-loaded niosomes were successfully developed, entirely characterized, and optimized. Further evaluation of the optimized formula was conducted regarding its stability and ex vivo cytotoxicity on different cell lines. The optimized niosomal vesicles were then incorporated in gel base matrix and investigated by sequential ex vivo (skin permeation and deposition) and in vivo (skin irritation and antipsoriatic activity using mouse tail model) experiments. The optimized Act-loaded niosomes (span 60:cholesterol molar ratio 1:1) were spherical in shape and exhibited the highest entrapment efficiency (90.32±3.80%) with appropriate nanosize and zeta potential of 369.73±45.45 nm and −36.33±1.80 mV, respectively. Encapsulation of the drug in the nanovesicles was further emphasized by differential scanning calorimetric and powder X-ray diffraction studies. After 3 months storage at 4±1°C, the optimized formula preserved its stability. Act nano niosomal gel produced a remarkable enhanced ex vivo permeation profile up to 30 h and significant drug deposition in the viable epidermal–dermal layers compared with those of Act gel. The pronounced antipsoriatic activity of the medicated nano niosomes was proved ex vivo in HaCaT cells (a keratinocyte cell line). Topical application of Act nano niosomal gel to mouse tail model further established its distinct in vivo antipsoriatic superiority in terms of significantly higher orthokeratosis, drug activity, and reduction in epidermal thickness compared with the control and other gel formulations. Also, negligible skin irritation and better skin tolerability of Act nanovesicular gel were revealed by primary irritation index and histopathologic examination.

RETRACTED: Intranasal Niosomal In Situ Gel as a Promising Approach for Enhancing Flibanserin Bioavailability and Brain Delivery: In Vitro Optimization and Ex Vivo/In Vivo Evaluation

“…For vesicle size diminution, the formed niosomal dispersion was subjected to sonication for 60 s using a Sonics Vibra Cell tapered microtip of amplitude 40%, 750 watt, 20 KHZ (Sonics & materials Inc., Newtown, CT, USA). The niosomal dispersion was kept overnight at 4 °C for maturation prior to further investigations [ 22 , 23 ].…”

Recent Advances in the Structural Design of Photosensitive Agent Formulations Using “Soft” Colloidal Nanocarriers

“…In the therapy of psoriasis, oral administration of drugs is inadvisable due to side effects such as hepatic toxicity. For this reason, the topical administration is necessary for safe treatment along with the increased drug local bioavailability at the diseases site [113,126]. Rajitha et al [109] prepared an effective topical formulation of methotrexate-loaded nanoemulsion from chaulmoogra oil.…”

Transdermal patches: Design and current approaches to painless drug delivery

“…Inspection is carried out visually on the sites of application for any possible changes in terms of skin erythema and edema. Draize scale can be used to score the changes involving erythema and edema between 0 and 4 (101). This is rated based on the degree of severity of skin reactions (101).…”

“…Draize scale can be used to score the changes involving erythema and edema between 0 and 4 (101). This is rated based on the degree of severity of skin reactions (101). PII is calculated according to the following equation:…”