Fabrication of novel elastosomes for boosting the transdermal delivery of diacerein: statistical optimization, ex-vivo permeation, in-vivo skin deposition and pharmacokinetic assessment compared to oral formulation

Abstract

Diacerein (DCN) is a hydrophobic osteoarthritis (OA) drug with short half-life and low oral bioavailability. Furthermore, DCN oral administration is associated with diarrhea which represents obstacle against its oral use. Hence, this article aimed at developing elastosomes (edge activator (EA)-based vesicular nanocarriers) as a novel transdermal system for delivering DCN efficiently and avoiding its oral problems. For achieving this goal, elastosomes were prepared according to 41.21 full factorial design using different EAs in varying amounts. The prepared formulae were characterized regarding their entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and deformability index (DI). Desirability function was employed using Design-Expert® software to select the optimal elastosomes (E1) which showed EE% of 96.25 ± 2.19%, PS of 506.35 ± 44.61 nm, PDI of 0.46 ± 0.09, ZP of −38.65 ± 0.91 mV, and DI of 12.74 ± 2.63 g. In addition, E1 was compared to DCN-loaded bilosomes and both vesicles exhibited superior skin permeation potential and retention capacity compared to drug suspension. In-vivo histopathological study was performed which ensured the safety of E1 for topical application. Furthermore, the pharmacokinetic study conducted in albino rabbits demonstrated that there was no significant difference in the rate and extent of DCN absorption from topically applied E1 compared to oral suspension. Multiple level C in-vitro in-vivo correlation showed good correlation between in-vitro release and in-vivo drug performance for E1 and DCN oral suspension. Overall, results confirmed the admirable potential of E1 to be utilized as novel carrier for transdermal delivery of DCN and bypassing its oral side effects.

Use of Novasomes as a Vesicular Carrier for Improving the Topical Delivery of Terconazole: In Vitro Characterization, In Vivo Assessment and Exploratory Clinical Experimentation

“…Group I (control), group II (TCZ suspension), and group III (the optimum novasomes). The formulations in groups II and III were applied topically onto the rat skin three times per day for one week, 15 then the animals were killed and the skin was removed and examined based on the steps described by Aziz et al 24 …”

Response Surface Optimization of Ultra-Elastic Nanovesicles Loaded with Deflazacort Tailored for Transdermal Delivery: Accentuated Bioavailability and Anti-Inflammatory Efficacy

“…UENVs are vesicles with ultra-flexible lipid bilayer membranes which make them highly deformable so that they can penetrate through the tight pores in the epidermis. 12 UENVs contain edge activators which make destabilization in the liposomal lipid bilayer leading to increase in the flexibility of liposomes. The drug delivery by using UENVs as vesicular carriers across the skin is more enhanced compared to that of conventional liposomes.…”

Gellan Gum-Based Hydrogel for the Transdermal Delivery of Nebivolol: Optimization and Evaluation

“…An open-ended circular holder (diameter 1 cm) with wings was fixed on the skin surface, optimized gel (F7) was applied uniformly (1 g in 1 cm 2 area containing 2.5 mg of nebivolol) and was covered with Parafilm. For the second group, nebivolol suspension in phosphate buffer saline (1 mL) was administered perorally (1 mg/kg of nebivolol) using intragastric gavage [32]. The dose of nebivolol was calculated according to the standard human dose (10 mg), using an equation described in the literature [33].…”