Abstract：
PURPOSE:We examined the ability of a protein transduction domain (PTD), YARA, to penetrate in the skin and carry a conjugated peptide, P20. The results with YARA were compared to those of a well-known PTD (TAT) and a control, nontransducing peptide (YKAc). The combined action of PTDs and lipid penetration enhancers was also tested. METHODS:YARA, TAT, YKAc, P20, YARA-P20, and TAT-P20 were synthesized by Fmoc chemistry. Porcine ear skin mounted in a Franz diffusion cell was used to assess the topical and transdermal delivery of fluorescently tagged peptides in the presence or absence of lipid penetration enhancers (monoolein or oleic acid). The peptide concentrations in the skin (topical delivery) and receptor phase (transdermal delivery) were assessed by spectrofluorimetry. Fluorescence microscopy was used to visualize the peptides in different skin layers. RESULTS:YARA and TAT, but not YKAc, penetrated abundantly in the skin and permeated modestly across this tissue. Monoolein and oleic acid did not enhance the topical and transdermal delivery of TAT or YARA but increased the topical delivery of YKAc. Importantly, YARA and TAT carried a conjugated peptide, P20, into the skin, but the transdermal delivery was very small. Fluorescence microscopy confirmed that free and conjugated PTDs reached viable layers of the skin. CONCLUSIONS:YARA and TAT penetrate in the porcine ear skin in vitro and carry a conjugated model peptide, P20, with them. Thus, the use of PTDs can be a useful strategy to increase topical delivery of peptides for treatment of cutaneous diseases.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Lopes LB,Brophy CM,Furnish E,Flynn CR,Sparks O,Komalavilas P,Joshi L,Panitch A,Bentley MVdoi
10.1007/s11095-005-2591-xsubject
Has Abstractpub_date
2005-05-01 00:00:00pages
750-7issue
5eissn
0724-8741issn
1573-904Xjournal_volume
22pub_type
杂志文章abstract：PURPOSE:Polyesters with hydrophilic domains, i.e., poly(D,L-lactic-co-glycolic-co-hydroxymethyl glycolic acid) (PLGHMGA) and a multiblock copolymer of poly(ε-caprolactone)-PEG-poly(ε-caprolactone) and poly(L-lactide) ((PC-PEG-PC)-(PL)) are expected to cause less acylation of encapsulated peptides than fully hydrophobic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1022202926073
更新日期：2003-01-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：2002-01-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015855613083
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015880218535
更新日期：1991-07-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：1996-12-01 00:00:00
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更新日期：2009-05-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：2004-03-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9369-2
更新日期：2007-11-01 00:00:00
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journal_title：Pharmaceutical research
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doi：10.1023/a:1013081710135
更新日期：2001-09-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0277-5
更新日期：2010-12-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9805-y
更新日期：2009-04-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000041449.46054.b4
更新日期：2004-09-01 00:00:00
abstract：:Inhibition of efflux pumps is an emerging approach in cancer therapy and drug delivery. Since it has been discovered that polymeric pharmaceutical excipients such as Tweens or Pluronics can inhibit efflux pumps, various other polymers have been investigated regarding their potential efflux pump inhibitory activity. Am...
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pub_type： 杂志文章,评审
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更新日期：2008-03-01 00:00:00
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更新日期：2015-09-01 00:00:00
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journal_title：Pharmaceutical research
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doi：10.1007/s11095-007-9477-z
更新日期：2008-02-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：1993-09-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：1996-04-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1013002414678
更新日期：2001-09-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：1999-02-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：1994-04-01 00:00:00
abstract：PURPOSE:To examine the iontophoretic delivery of ALA as a function of pH and to determine the principal mechanisms responsible for its electrotransport. METHODS:Anodal iontophoretic transport of ALA was measured as a function of its concentration and pH of the donor solution. Experiments were performed in vitro using ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：2001-03-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：2006-10-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016382426347
更新日期：1985-03-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 社论
doi：10.1007/s11095-007-9463-5
更新日期：2007-12-01 00:00:00
