title: Localized delivery of a lipophilic proteasome inhibitor into human skin for treatment of psoriasis.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  PTTC can be delivered intradermally to potentially treat psoriasis.
authors.affiliation: a College of Pharmacy, Mercer University , Atlanta , GA , USA .
authors.forename: Meera
authors.initials: M
authors.lastname: Gujjar
authors.affiliation: b Department of Dermatology , Emory University Winship Cancer Institute , Atlanta , GA , USA .|c Atlanta VA Medical Center , Decatur , GA , USA , and.
authors.forename: Jack
authors.initials: J
authors.lastname: Arbiser
authors.affiliation: d Accuitis, Inc. , Cumming , GA , USA.
authors.forename: Rick
authors.initials: R
authors.lastname: Coulon
authors.affiliation: a College of Pharmacy, Mercer University , Atlanta , GA , USA .
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Banga
mesh_terms: D000279:Administration, Cutaneous; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004655:Emulsions; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D010666:Phenylpropionates / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D011409:Propylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D061988:Proteasome Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility
chemical_list: D003879:Dermatologic Agents; D004655:Emulsions; D015850:Interleukin-6; D010666:Phenylpropionates; D011409:Propylene Glycols; D061988:Proteasome Inhibitors; C000613260:pentaerythritol tetrakis(3,5-di-tert-butyl-4-hydroxyhydrocinnamate)
keywords: Dermal delivery; microneedles; skin irritation