Formulation Development and Optimization of Crisaborole-Loaded Deformable Transferosomes for the Topical Management of Psoriasis

Research Article

Abstract

Psoriasis is a chronic inflammatory dermatosis characterized by keratinocyte hyperproliferation and a severely compromised epidermal barrier, which together restrict the clinical efficacy of conventional topical therapeutics. This study details the development, optimization, and physiochemical characterization of ultra-deformable transferosomes loaded with the selective phosphodiesterase-4 inhibitor, crisaborole, to enhance localized dermal delivery. Prepared via thin-film hydration using soya lecithin and polysorbate 80 (Tween 80), the vesicular carriers were statistically optimized using a three-factor, three-level Box–Behnken experimental design. The optimized transferosomal dispersion was subsequently incorporated into structural gel and ointment matrices to evaluate their clinical applicability. The optimized vesicular suspension exhibited an average hydrodynamic diameter of 167.58 nm, a stable zeta potential of -29.6 mV, and a high drug entrapment efficiency of 94.07%. Morphological analysis highlighted dehydration-induced crystallization phenomena typical of saline-buffered vesicular suspensions under high-vacuum electron microscopy. Rheological and physical profiling of the developed transferosomal gel (TFSOF 3) and ointment (TFSOF 3) confirmed appropriate spreadability, skin-compatible pH, and sustained-release profiles, achieving cumulative drug releases of 90.49% and 95.46% over extended periods, respectively. Mathematical modeling of the release profiles indicated a primary adherence to zero-order and Higuchi diffusion kinetics. In vivo dermatological tolerability and safety studies on Wistar rats confirmed the absence of skin irritation, while accelerated stability testing under International Council for Harmonisation guidelines established robust physical and chemical integrity over three months. These findings indicate that ultra-deformable transferosomes represent a highly efficient and safe topical nanocarrier platform for the targeted, sustained delivery of crisaborole in the management of plaque psoriasis