title: Impact of different vehicles for laser-assisted drug permeation via skin: full-surface versus fractional ablation.
abstract: OBJECTIVE
  This study aimed to assess impact of different vehicles for laser-assisted skin drug delivery. We also tried to uncover the mechanisms by which different vehicles affect laser-aided skin permeation.
  
  
  METHODS
  Full-surface ablative (conventional) and fractional lasers were used to irradiate nude mouse skin. Imiquimod and 5-aminolevulinic acid (ALA) were used as lipophilic and hydrophilic permeants. Vehicles employed included water with 40% polyethylene glycol 400 (PEG 400), propylene glycol (PG), and ethanol. Lipid nanoparticles were also utilized as carriers.
  
  
  RESULTS
  In vitro permeation profiles showed improvement in imiquimod flux with conventional laser (2.5 J/cm2) producing a 12-, 9-, and 5-fold increase when loading imiquimod in 40% PEG400, PG, and ethanol, respectively, as compared with intact skin. Nanoparticulate delivery by laser produced a 6-fold enhancement in permeation. Fractional laser produced less enhancement of imiquimod delivery than conventional laser. Laser exposure increased follicular imiquimod accumulation from 0.80 to 5.81 μg/cm2. ALA permeation from aqueous buffer, PEG 400, and PG with conventional laser treatment was 641-, 445-, and 104-fold superior to passive control. In vivo skin deposition of topically applied ALA examined by confocal microscopy indicated the same trend as the in vitro experiment, with aqueous buffer showing the greatest proporphyllin IX signaling. Diffusion of cosolvent molecules into ablated skin and drug partitioning from vehicle to skin are two predominant factors controlling laser-assisted delivery. In contrast to conventional laser, lateral drug diffusion was anticipated for fractional laser.
  
  
  CONCLUSIONS
  Our results suggest that different drug delivery vehicles substantially influence drug penetration enhanced by lasers.
authors.forename: Woan-Ruoh
authors.initials: WR
authors.lastname: Lee
authors.forename: Shing-Chuan
authors.initials: SC
authors.lastname: Shen
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Aljuffali
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Li
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Fang
mesh_terms: D000279:Administration, Cutaneous; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D000634:Aminoquinolines / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D057927:Hydrophobic and Hydrophilic Interactions; D000077271:Imiquimod; D007834:Lasers; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D010539:Permeability; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000502:physiology*; D014867:Water / Q000737:chemistry
chemical_list: D000634:Aminoquinolines; D014677:Pharmaceutical Vehicles; D014867:Water; D011092:Polyethylene Glycols; D019946:Propylene Glycol; D000622:Aminolevulinic Acid; D000077271:Imiquimod
references.citation: Br J Dermatol. 2000 Sep;143(3):564-72
references.pmid: 10971330
references.citation: Eur J Pharm Biopharm. 2008 Oct;70(2):633-40
references.pmid: 18577447
references.citation: J Invest Dermatol. 2003 Jul;121(1):104-9
references.pmid: 12839570
references.citation: J Am Acad Dermatol. 2013 Jan;68(1):103-12
references.pmid: 23110966
references.citation: Adv Drug Deliv Rev. 2004 Jan 13;56(1):77-94
references.pmid: 14706446
references.citation: J Pharm Sci. 2013 Feb;102(2):593-603
references.pmid: 23192692
references.citation: J Invest Dermatol. 2005 Aug;125(2):264-9
references.pmid: 16098036
references.citation: Int J Pharm. 2009 Jan 5;365(1-2):26-33
references.pmid: 18801420
references.citation: Eur J Pharm Biopharm. 2011 Aug;78(3):408-14
references.pmid: 21397689
references.citation: Eur J Pharm Sci. 2007 Mar;30(3-4):280-7
references.pmid: 17188470
references.citation: J Pharm Sci. 2008 Jan;97(1):185-97
references.pmid: 17497726
references.citation: Toxicol Lett. 2012 Jun 1;211(2):150-8
references.pmid: 22483991
references.citation: Br J Dermatol. 2007 Dec;157 Suppl 2:8-13
references.pmid: 18067624
references.citation: J Control Release. 2006 Oct 27;115(3):344-53
references.pmid: 17005286
references.citation: Br J Dermatol. 2012 Jun;166(6):1160-9
references.pmid: 22296284
references.citation: J Invest Dermatol. 2006 Jun;126(6):1251-5
references.pmid: 16557235
references.citation: Skin Pharmacol Physiol. 2011;24(1):22-6
references.pmid: 20616625
references.citation: J Control Release. 2012 Nov 10;163(3):335-41
references.pmid: 23000695
references.citation: Adv Drug Deliv Rev. 2007 Jul 10;59(6):427-43
references.pmid: 17544165
references.citation: J Am Acad Dermatol. 2007 Mar;56(3):422-5
references.pmid: 17184874
references.citation: Skin Pharmacol Physiol. 2009;22(4):225-30
references.pmid: 19648784
references.citation: J Control Release. 2010 Jul 14;145(2):124-33
references.pmid: 20359510
references.citation: J Biomed Opt. 2013 Jun;18(6):061214
references.pmid: 23224242
references.citation: Clin Exp Dermatol. 2003 Nov;28 Suppl 1:1-3
references.pmid: 14616801
references.citation: Pharm Res. 2013 Mar;30(3):792-802
references.pmid: 23138262
references.citation: Int J Pharm. 2001 May 21;219(1-2):95-105
references.pmid: 11337170
references.citation: J Am Acad Dermatol. 2010 Apr;62(4):582-90
references.pmid: 20133013
references.citation: Int J Pharm. 2006 Jan 13;307(2):318-25
references.pmid: 16300913
references.citation: J Control Release. 2011 Aug 10;153(3):240-8
references.pmid: 21435360
references.citation: J Control Release. 2005 Oct 20;107(3):495-501
references.pmid: 16087267
references.citation: Lasers Surg Med. 2008 Sep;40(7):468-76
references.pmid: 18727021
references.citation: Curr Pharm Des. 2011;17(32):3548-59
references.pmid: 22074426
references.citation: Pharm Res. 2013 Feb;30(2):435-46
references.pmid: 23070602
references.citation: J Control Release. 2012 Apr 10;159(1):43-51
references.pmid: 22261281
references.citation: Pharm Dev Technol. 1999 Jan;4(1):35-43
references.pmid: 10027211
references.citation: Eur J Pharm Biopharm. 2010 May;75(1):48-55
references.pmid: 20083197
references.citation: J Biomed Opt. 2013 Jun;18(6):61228
references.pmid: 23429836