title: Percutaneous delivery of α-melanocyte-stimulating hormone for the treatment of imiquimod-induced psoriasis.
abstract: OBJECTIVE
  α-Melanocyte-stimulating hormone (α-MSH) is an endogenous peptide hormone with anti-inflammatory responses. We developed topical formulation(s) of α-MSH to reduce psoriasis-related inflammation.
  
  
  METHODS
  Transcutol (TC) and n-methyl 2-pyrrolidone (NMP) were used to formulate a gel for α-MSH. Skin permeation and dermal microdialysis of the solution and optimized gel were performed. The inflammatory response of α-MSH gel was investigated in imiquimod-induced psoriasis mouse model. Histology and immunohistochemistry were then performed on treated skin.
  
  
  RESULTS
  Solution comprising 50%w/w TC and 10%w/w NMP showed higher (p < 0.05) skin retention (0.27 ± 0.024 µg of α-MSH/mg of skin) than solutions containing either 50% w/w TC or 10% w/w NMP at 24 h. Dispersion of α-MSH in Carbopol Ultrez 10 produced a uniform dispersion. α-MSH gel showed pseudoplastic flow with thixotropic behavior. Dermal microdialysis results suggested that skin permeation of gel after 5 h was 1.9-folds higher than the solution. Further, gel-treated psoriatic-like plaque skin sections showed significant (p < 0.05) decrease in the expression of a melanocortin receptor, in the psoriasis area and severity index score and transepidermal water loss compared to the solution.
  
  
  CONCLUSIONS
  TC, NMP and Carbopol Ultrez 10 form a stable gel with improved skin permeation of α-MSH for a reduction in psoriasis-associated inflammation.
authors.affiliation: a College of Pharmacy and Pharmaceutical Sciences , Florida A&M University , Tallahassee , FL , USA .
authors.forename: Punit P
authors.initials: PP
authors.lastname: Shah
authors.affiliation: a College of Pharmacy and Pharmaceutical Sciences , Florida A&M University , Tallahassee , FL , USA .
authors.forename: Pinaki R
authors.initials: PR
authors.lastname: Desai
authors.affiliation: a College of Pharmacy and Pharmaceutical Sciences , Florida A&M University , Tallahassee , FL , USA .
authors.forename: Cedar H A
authors.initials: CH
authors.lastname: Boakye
authors.affiliation: b Dr. Reddy's Laboratories, Integrated Product Development , Bachupallyi , Hyderabad , India , and.
authors.forename: Ram
authors.initials: R
authors.lastname: Patlolla
authors.affiliation: a College of Pharmacy and Pharmaceutical Sciences , Florida A&M University , Tallahassee , FL , USA .
authors.forename: Loice C
authors.initials: LC
authors.lastname: Kikwai
authors.affiliation: c Department of Pharmaceutical Sciences , Harrison School of Pharmacy, Auburn University , Auburn , AL , USA.
authors.forename: R Jayachandra
authors.initials: RJ
authors.lastname: Babu
authors.affiliation: a College of Pharmacy and Pharmaceutical Sciences , Florida A&M University , Tallahassee , FL , USA .
authors.forename: Mandip
authors.initials: M
authors.lastname: Singh
mesh_terms: D000279:Administration, Cutaneous; D000634:Aminoquinolines / Q000633:toxicity; D000818:Animals; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005026:Ethylene Glycols / Q000737:chemistry; D005782:Gels; D000077271:Imiquimod; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption; D000521:alpha-MSH / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000634:Aminoquinolines; D004337:Drug Carriers; D005026:Ethylene Glycols; D005782:Gels; D000521:alpha-MSH; C010111:carbitol; D000077271:Imiquimod
keywords: melanocortin receptor; psoriasis; skin permeation; topical gel formulation; α-MSH