Enhancing topical acitretin delivery: formulation and evaluation of solid lipid nanoparticles for efficient skin therapy through in vitro and ex vivo testing

Oral vitamin-A derivative acitretin treats severe psoriasis. Oral capsules are commercially available preparation and have severe systemic adverse effects. This research involved the development, optimization, and characterization (in vitro and ex vivo) of a topical gel formulation of solid lipid nanoparticles (SLNPs) for the efficient delivery of acitretin to the skin. SLNPs with acitretin were prepared using hot homogenization with compritol ATO 888 and Tween 80. Optimization was done via a 3(2) factorial Box-Behnken design. SLNPs exhibit a vesicle size within the range of 181.53 +/- 1.727 to 409 +/- 1.019 nm, with a prominent encapsulation efficiency of 78.82% +/- 2.1% to 85.73% +/- 1.6%. Moreover, the developed SLNPs and SLNPs-based gel formulation demonstrate reliable storage stability over 3-month duration. The ex vivo skin permeation and deposition studies were conducted using cellophane membrane and rat skin, respectively. The results demonstrated a sustained release of the SLNP-based gels over an 8-h period, as well as a higher skin deposition compared to the plain acitretin gel. The acitretin SLNP in vitro release study demonstrated an 86.83% sustained drug release within 8 hours, whereas a plain gel exhibited a 92.5% drug release within 4 hours. Ex vivo drug deposition testing of SLNP-based gel formulation demonstrate a total of 0.056 mg/cm(2) of acitretin skin deposition, while the commercially available gel had only 0.012 mg/cm(2). Acitretin SLNPs show promising potential for treating psoriasis more effectively, offering a safe alternative to topical acitretin administration with enhanced pharmacological effects and reduced systemic toxicity compared to oral intake.