Meera Gujjar1, Jack Arbiser2,3, Rick Coulon4, Ajay K Banga1. 1. a College of Pharmacy, Mercer University , Atlanta , GA , USA . 2. b Department of Dermatology , Emory University Winship Cancer Institute , Atlanta , GA , USA . 3. c Atlanta VA Medical Center , Decatur , GA , USA , and. 4. d Accuitis, Inc. , Cumming , GA , USA.
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.
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.
Authors: R M Grossman; J Krueger; D Yourish; A Granelli-Piperno; D P Murphy; L T May; T S Kupper; P B Sehgal; A B Gottlieb Journal: Proc Natl Acad Sci U S A Date: 1989-08 Impact factor: 11.205
Authors: Wendy A Goodman; Alan D Levine; Jessica V Massari; Hideaki Sugiyama; Thomas S McCormick; Kevin D Cooper Journal: J Immunol Date: 2009-07-31 Impact factor: 5.422