Enhanced pulmonary absorption of a macromolecule through coupling to a sequence-specific phage display-derived peptide

Christopher J. Morris; Mathew W. Smith; Peter C. Griffiths; Neil B. McKeown; Mark Gumbleton

doi:10.1016/j.jconrel.2010.12.003

Enhanced pulmonary absorption of a macromolecule through coupling to a sequence-specific phage display-derived peptide

Christopher J. Morris, Mathew W. Smith, Peter C. Griffiths, Neil B. McKeown, Mark Gumbleton^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

With the aim of identifying a peptide sequence that promotes pulmonary epithelial transport of macromolecule cargo we used a stringent peptide-phage display library screening protocol against rat lung alveolar epithelial primary cell cultures. We identified a peptide-phage clone (LIP-1) displaying the disulphide-constrained 7-met peptide sequence. C-TSGTHPR-C, that showed significant pulmonary epithelial translocation across highly restrictive polarised cell monolayers. Cell biological data supported a differential alveolar epithelial cell interaction of the LIP-1 peptide-phage clone and the corresponding free synthetic LIP-1 peptide. Delivering select phage-clones to the intact pulmonary barrier of an isolated perfused rat lung (IPRL) resulted in 8.7% of lung deposited LIP-1 peptide-phage clone transported from the IPRL airways to the vasculature compared (p

Original language	English
Pages (from-to)	83-94
Number of pages	12
Journal	Journal of Controlled Release
Volume	151
Issue number	1
DOIs	https://doi.org/10.1016/j.jconrel.2010.12.003
Publication status	Published - 10 Apr 2011

Keywords

Phage-display
Peptide
Dendrimer
Lung
Absorption
Isolated perfused lung
IN-VIVO
MAMMALIAN-CELLS
GENE DELIVERY
ALVEOLAR EPITHELIUM
TARGETING LIGANDS
DRUG-DELIVERY
LUNG
TRANSPORT
VECTORS
LIBRARIES

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10.1016/j.jconrel.2010.12.003

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title = "Enhanced pulmonary absorption of a macromolecule through coupling to a sequence-specific phage display-derived peptide",

abstract = "With the aim of identifying a peptide sequence that promotes pulmonary epithelial transport of macromolecule cargo we used a stringent peptide-phage display library screening protocol against rat lung alveolar epithelial primary cell cultures. We identified a peptide-phage clone (LIP-1) displaying the disulphide-constrained 7-met peptide sequence. C-TSGTHPR-C, that showed significant pulmonary epithelial translocation across highly restrictive polarised cell monolayers. Cell biological data supported a differential alveolar epithelial cell interaction of the LIP-1 peptide-phage clone and the corresponding free synthetic LIP-1 peptide. Delivering select phage-clones to the intact pulmonary barrier of an isolated perfused rat lung (IPRL) resulted in 8.7% of lung deposited LIP-1 peptide-phage clone transported from the IPRL airways to the vasculature compared (p",

keywords = "Phage-display, Peptide, Dendrimer, Lung, Absorption, Isolated perfused lung, IN-VIVO, MAMMALIAN-CELLS, GENE DELIVERY, ALVEOLAR EPITHELIUM, TARGETING LIGANDS, DRUG-DELIVERY, LUNG, TRANSPORT, VECTORS, LIBRARIES",

author = "Morris, {Christopher J.} and Smith, {Mathew W.} and Griffiths, {Peter C.} and McKeown, {Neil B.} and Mark Gumbleton",

year = "2011",

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day = "10",

doi = "10.1016/j.jconrel.2010.12.003",

language = "English",

volume = "151",

pages = "83--94",

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T1 - Enhanced pulmonary absorption of a macromolecule through coupling to a sequence-specific phage display-derived peptide

AU - Morris, Christopher J.

AU - Smith, Mathew W.

AU - Griffiths, Peter C.

AU - McKeown, Neil B.

AU - Gumbleton, Mark

PY - 2011/4/10

Y1 - 2011/4/10

N2 - With the aim of identifying a peptide sequence that promotes pulmonary epithelial transport of macromolecule cargo we used a stringent peptide-phage display library screening protocol against rat lung alveolar epithelial primary cell cultures. We identified a peptide-phage clone (LIP-1) displaying the disulphide-constrained 7-met peptide sequence. C-TSGTHPR-C, that showed significant pulmonary epithelial translocation across highly restrictive polarised cell monolayers. Cell biological data supported a differential alveolar epithelial cell interaction of the LIP-1 peptide-phage clone and the corresponding free synthetic LIP-1 peptide. Delivering select phage-clones to the intact pulmonary barrier of an isolated perfused rat lung (IPRL) resulted in 8.7% of lung deposited LIP-1 peptide-phage clone transported from the IPRL airways to the vasculature compared (p

AB - With the aim of identifying a peptide sequence that promotes pulmonary epithelial transport of macromolecule cargo we used a stringent peptide-phage display library screening protocol against rat lung alveolar epithelial primary cell cultures. We identified a peptide-phage clone (LIP-1) displaying the disulphide-constrained 7-met peptide sequence. C-TSGTHPR-C, that showed significant pulmonary epithelial translocation across highly restrictive polarised cell monolayers. Cell biological data supported a differential alveolar epithelial cell interaction of the LIP-1 peptide-phage clone and the corresponding free synthetic LIP-1 peptide. Delivering select phage-clones to the intact pulmonary barrier of an isolated perfused rat lung (IPRL) resulted in 8.7% of lung deposited LIP-1 peptide-phage clone transported from the IPRL airways to the vasculature compared (p

KW - Phage-display

KW - Peptide

KW - Dendrimer

KW - Lung

KW - Absorption

KW - Isolated perfused lung

KW - IN-VIVO

KW - MAMMALIAN-CELLS

KW - GENE DELIVERY

KW - ALVEOLAR EPITHELIUM

KW - TARGETING LIGANDS

KW - DRUG-DELIVERY

KW - LUNG

KW - TRANSPORT

KW - VECTORS

KW - LIBRARIES

U2 - 10.1016/j.jconrel.2010.12.003

DO - 10.1016/j.jconrel.2010.12.003

M3 - Article

VL - 151

SP - 83

EP - 94

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 1

ER -

Enhanced pulmonary absorption of a macromolecule through coupling to a sequence-specific phage display-derived peptide

Abstract

Keywords

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