Journal Article

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

Abd El-Gawad, Abd El-Gawad, Hamed, Mohammed, El-Sheakh, Ahmed, Abo El-Magd, Noha, Abu Hashim, Irhan

2018

Overview

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.

• Publisher: Dove Medical Press Limited,Taylor & Francis Ltd,Dove Medical Press
• Subject: Acitretin / Acitretin - pharmacology / Acitretin - therapeutic use / Acne / Analysis / Animal experimentation / Animals / anti-psoriatic activity / Calorimetry, Differential Scanning / Cell Death - drug effects / Cell Line / Dermatologic agents / Disease / Drug Carriers - chemistry / Drug Compounding / Drug delivery systems / drug deposition / Drug Stability / Drugs / Gels - chemistry / HaCaT cells / Humans / Hydration / Kinetics / Lipids / Liposomes - chemistry / Liposomes - ultrastructure / Male / Mice / mouse tail model / nano vesicular gel / Nanoparticles - chemistry / Original Research / Particle Size / Pharmacy / Psoriasis / Psoriasis - drug therapy / Psoriasis - pathology / Rats / Retinoids / Retirement benefits / Skin / Skin - drug effects / Skin - metabolism / Skin - pathology / Skin Absorption - drug effects / Skin Irritancy Tests / Solubility / Static Electricity / Surface active agents / Transdermal drug delivery systems / X-Ray Diffraction