title: Tat peptide-admixed elastic liposomal formulation of hirsutenone for the treatment of atopic dermatitis in NC/Nga mice.
abstract: BACKGROUND
  The aim of the present study was to enhance a topical delivery of hirsutenone (HST), a naturally occuring immunomodulator, employing Tat peptide-admixed elastic liposomes (EL/T).
  
  
  METHODS
  HST-loaded EL, consisting of phosphatidylcholine and Tween 80 (85:15 w/w%), were prepared using thin film hydration method. By adding Tat peptide to EL (0.16 w/w%), EL/T were formulated. The in vitro skin permeation of HST was examined using a Franz diffusion cell mounted with depilated mouse skin. Lesions for atopic dermatitis (AD) were induced by a topical application of diphenylcyclopropenone to NC/Nga mice. Therapeutic improvements of AD were evaluated by clinical skin severity scores. Immunological analyses on inducible nitric oxide synthase and cyclooxygenase-2 levels in the skin and interleukin (IL)-4, IL-13, immunoglobulin E, and eosinophil levels in the blood were also performed.
  
  
  RESULTS
  EL systems were superior to conventional cream, revealing greater flux values in a permeation study. The addition of Tat peptide further increased the skin permeation of HST. In an efficacy study with AD-induced NC/Nga mice, an HST-containing EL/T formulation brought a significant improvement in both skin severity score and immune-related responses for the levels of nitric oxide synthase, cyclooxygenase-2, IL-4, IL-13, immunoglobulin E, and eosinophils.
  
  
  CONCLUSIONS
  A novel EL/T formulation was successfully developed for topical delivery of HST to treat AD.
authors.affiliation: College of Pharmacy, Chung- Ang University, Heuksuk-dong, Dongjak-gu, Seoul, South Korea.
authors.forename: Myung Joo
authors.initials: MJ
authors.lastname: Kang
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: Eum
authors.forename: Mi Sook
authors.initials: MS
authors.lastname: Jeong
authors.forename: Sang Han
authors.initials: SH
authors.lastname: Park
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Moon
authors.forename: Mean Hyung
authors.initials: MH
authors.lastname: Kang
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Kim
authors.forename: Sun Eun
authors.initials: SE
authors.lastname: Choi
authors.forename: Min Won
authors.initials: MW
authors.lastname: Lee
authors.forename: Do Ik
authors.initials: DI
authors.lastname: Lee
authors.forename: Hyoweon
authors.initials: H
authors.lastname: Bang
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
authors.forename: Seong Soo
authors.initials: SS
authors.lastname: Joo
authors.forename: Kapsok
authors.initials: K
authors.lastname: Li
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Lee
authors.forename: Seong Jun
authors.initials: SJ
authors.lastname: Seo
authors.forename: Young Wook
authors.initials: YW
authors.lastname: Choi
mesh_terms: D000818:Animals; D002396:Catechols / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D036381:Diarylheptanoids / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D015696:Gene Products, tat / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D007073:Immunoglobulin E / Q000097:blood; D018793:Interleukin-13 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010713:Phosphatidylcholines; D011136:Polysorbates; D012869:Skin Absorption / Q000187:drug effects
chemical_list: D002396:Catechols; D036381:Diarylheptanoids; D015696:Gene Products, tat; D018793:Interleukin-13; D008081:Liposomes; D010713:Phosphatidylcholines; D011136:Polysorbates; C508777:hirsutenone; D015847:Interleukin-4; D007073:Immunoglobulin E; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2
references.citation: J Allergy Clin Immunol. 2000 Jul;106(1 Pt 1):159-66
references.pmid: 10887319
references.citation: Biochim Biophys Acta. 1998 Jan 19;1368(2):201-15
references.pmid: 9459598
references.citation: Pharm Res. 1991 Sep;8(9):1144-50
references.pmid: 1838597
references.citation: Int J Pharm. 2003 Jun 4;258(1-2):141-51
references.pmid: 12753761
references.citation: J Nutr Sci Vitaminol (Tokyo). 2006 Aug;52(4):293-6
references.pmid: 17087057
references.citation: Lancet. 2003 Jan 11;361(9352):151-60
references.pmid: 12531593
references.citation: Biol Pharm Bull. 2010;33(1):100-6
references.pmid: 20045944
references.citation: Nature. 1985 Jul 11-17;316(6024):150-2
references.pmid: 4010786
references.citation: Int Immunopharmacol. 2003 Sep;3(9):1313-24
references.pmid: 12890429
references.citation: Curr Opin Immunol. 2000 Dec;12(6):641-6
references.pmid: 11102766
references.citation: Expert Opin Drug Deliv. 2006 Nov;3(6):713-26
references.pmid: 17076594
references.citation: Int J Pharm. 1999 Nov 10;190(1):63-71
references.pmid: 10528098
references.citation: Eur J Pharmacol. 2009 Jul 1;614(1-3):98-105
references.pmid: 19409888
references.citation: J Allergy Clin Immunol. 1995 Sep;96(3):302-18; quiz 319
references.pmid: 7560632
references.citation: Eur J Pharm Biopharm. 2008 Feb;68(2):441-5
references.pmid: 18035527
references.citation: Chem Pharm Bull (Tokyo). 2005 Dec;53(12):1519-23
references.pmid: 16327181
references.citation: J Invest Dermatol. 2004 Nov;123(5):902-10
references.pmid: 15482478
references.citation: Biochim Biophys Acta. 2001 Oct 1;1514(2):191-205
references.pmid: 11557020
references.citation: Int J Pharm. 2001 Jun 4;220(1-2):63-75
references.pmid: 11376968
references.citation: Int Arch Allergy Immunol. 2007;144(4):315-24
references.pmid: 17671391
references.citation: Evid Based Complement Alternat Med. 2005 Jun;2(2):191-199
references.pmid: 15937560
references.citation: Int J Pharm. 2000 Feb 25;196(1):63-74
references.pmid: 10675708
references.citation: Adv Drug Deliv Rev. 2002 Nov 1;54 Suppl 1:S41-55
references.pmid: 12460715
references.citation: Int Immunol. 1997 Mar;9(3):461-6
references.pmid: 9088984
references.citation: Pharm Res. 2005 May;22(5):750-7
references.pmid: 15906170
references.citation: Nat Med. 2000 Nov;6(11):1253-7
references.pmid: 11062537
references.citation: J Control Release. 2000 Apr 3;65(3):403-18
references.pmid: 10699298
references.citation: Int J Pharm. 2004 Nov 5;285(1-2):23-34
references.pmid: 15488676
references.citation: Exp Dermatol. 2010 Aug;19(8):e37-43
references.pmid: 19849716
references.citation: Hautarzt. 2003 May;54(5):418-23
references.pmid: 12719861
references.citation: Pharm Res. 2003 Jul;20(7):1022-30
references.pmid: 12880288
references.citation: Adv Drug Deliv Rev. 2004 Mar 27;56(5):581-7
references.pmid: 15019747
references.citation: Exp Dermatol. 2007 Dec;16(12):999-1006
references.pmid: 18031459
references.citation: Complement Ther Med. 2003 Dec;11(4):226-34
references.pmid: 15022655
references.citation: Biomaterials. 2006 Jun;27(18):3491-6
references.pmid: 16513163
references.citation: N Engl J Med. 1990 Sep 6;323(10):645-55
references.pmid: 2166915
references.citation: J Clin Invest. 1999 Oct;104(8):1097-105
references.pmid: 10525048
references.citation: Cancer Res. 2008 Mar 15;68(6):2043-50
references.pmid: 18339887
references.citation: Int J Pharm. 2001 Apr 17;217(1-2):13-24
references.pmid: 11292538
references.citation: FEBS Lett. 2006 Jan 23;580(2):385-92
references.pmid: 16380122
references.citation: J Allergy Clin Immunol. 2009 Feb;123(2):283-94; quiz 295-6
references.pmid: 19203652
references.citation: Pharm Res. 1996 Oct;13(10):1460-3
references.pmid: 8899835
references.citation: Int J Pharm. 2002 Jul 25;241(2):319-27
references.pmid: 12100859