Localized delivery of a lipophilic proteasome inhibitor into human skin for treatment of psoriasis

Abstract

Purpose: Pentaerythritol tetrakis (3,5-di-tert-butyl-4-hydroxyhydrocinnamate) (PTTC) is a cinnamate tetraester with proteasome inhibitor activity, which may be used as a topical treatment in psoriasis, but has a computed log P of 23. The objective of this in vitro study was to determine the intradermal delivery, skin irritation and potential efficacy of PTTC in treating psoriasis.

Methods: Solubility studies were performed to find a suitable vehicle for PTTC. Permeation studies were performed with microneedle-treated skin. A cell culture irritation test was dosed with a positive control, negative control and PTTC. An MTT assay was performed to evaluate cell viability and irritancy. Psoriatic cell culture was also dosed with PTTC and IL-6 levels were determined by ELISA.

Results: Solubility was greatest in dimethyl sulfoxide and ethyl pyruvate, with dimethyl sulfoxide delivering a greater amount (2343.41 ± 384.26 µg) into stratum corneum. PTTC alone as well as topical PTTC emulsion formulation were found to be non-irritant with cell viability of 69.0 ± 5.64% and 74.6 ± 5.03%, respectively. Treatment with neat PTTC slightly reduced IL-6 levels and PTTC emulsion significantly reduced IL-6 levels to 92.53 ± 12.74 pg/ml compared to basal levels (141.69 ± 8.41 pg/ml).

Conclusion: PTTC can be delivered intradermally to potentially treat psoriasis.

• Dermal delivery
• microneedles
• skin irritation

Declaration of interest

This project was funded by Accuitis, Inc.