Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation

Abstract

Apremilast (APR) is a selective phosphodiesterase 4 inhibitor administered orally in the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis. The low solubility and permeability of this drug hinder its dermal administration. The purpose of this study was to design and characterize an apremilast-loaded microemulsion (APR-ME) as topical therapy for local skin inflammation. Its composition was determined using pseudo-ternary diagrams. Physical, chemical and biopharmaceutical characterization were performed. Stability of this formulation was studied for 90 days. Tolerability of APR-ME was evaluated in healthy volunteers while its anti-inflammatory potential was studied using in vitro and in vivo models. A homogeneous formulation with Newtonian behavior and droplets of nanometric size and spherical shape was obtained. APR-ME released the incorporated drug following a first-order kinetic and facilitated drug retention into the skin, ensuring a local effect. Anti-inflammatory potential was observed for its ability to decrease the production of IL-6 and IL-8 in the in vitro model. This effect was confirmed in the in vivo model histologically by reduction in infiltration of inflammatory cells and immunologically by decrease of inflammatory cytokines IL-8, IL-17A and TNFα. Consequently, these results suggest that this formulation could be used as an attractive topical treatment for skin inflammation.

Development of a Topical Amphotericin B and Bursera graveolens Essential Oil-Loaded Gel for the Treatment of Dermal Candidiasis

“…In this study, the tested dilutions of AmB + BGEO gel did not induce relevant cytotoxic effects on cells after 24 h of incubation, which confirms high biocompatibility between the developed formulation and human keratinocytes. This result was confirmed by evaluation of biomechanical skin properties including TEWL and SCH, which allow analysis of the integrity of the skin barrier after exposure to physical or chemical agents [30,48]. The results revealed an increase in TEWL and SCH values 5 min after topical application of AmB + BGEO gel; however, a tendency to return to the basal state was observed in both parameters after 25 min of assay, suggesting that AmB + BGEO gel does not cause irritation or damage to the skin surface of volunteers.…”

Screening Anti-Inflammatory Effects of Flavanones Solutions

“…The hesperidin anti-inflammatory effects are correlated with inhibition of pro-inflammatory mediators, including cytokines (IL-8, IL-6, TNF-α, IL-1β), oxidative stress enzymes (iNOS, COX-2), prostaglandin, and intercellular adhesion molecules (ICAM) [53,54]. Continuing with our interest in the evaluation of the biological potential of flavanones [55], and in order to prove their anti-inflammatory effects, the gene expressions of IL-1β, IL-6, and TNF-α were analyzed in small sections of the rat ear tissue after FS1, FS1a-FS1d treatment. Overall, in our investigation, the FS1, FS1a-FS1d inhibited the production of IL-1β and IL-6 with respect to the positive control (Figure 4B,C).…”

Effect of Penetration Enhancers and Safety on the Transdermal Delivery of Apremilast in Skin

“…An analytical method was validated by high performance liquid chromatography (HPLC) for the identification and quantification of APR. The HPLC system is detailed in previous studies [ 21 ].…”

“…The effectiveness of this drug is limited by its side effects such as diarrhea, nausea, depression, and weight loss [ 18 ]. For this reason, the development of alternative administration forms, such as topical formulations, are attractive for local anti-inflammatory therapy; some research has covered this field with the development of nanocarriers incorporated into gels in some cases to improve the administration and bioavailability of APR [ 19 , 20 , 21 , 22 , 23 ].…”