Abstract：
PURPOSE:Treatment of acute lung injury (ALI) observed in Gram-negative sepsis represents an unmet medical need due to a high mortality rate and lack of effective treatment. Accordingly, we developed and characterized a novel nanomedicine against ALI. We showed that when human glucagon-like peptide 1(7-36) (GLP-1) self-associated with PEGylated phospholipid micelles (SSM), the resulting GLP1-SSM (hydrodynamic size, ~15 nm) exerted effective anti-inflammatory protection against lipopolysaccharide (LPS)-induced ALI in mice. METHODS:GLP1-SSM was prepared by incubating GLP-1 with SSM dispersion in saline and characterized using fluorescence spectroscopy and circular dichroism. Bioactivity was tested by in vitro cAMP induction, while in vivo anti-inflammatory effects were determined by lung neutrophil cell count, myeloperoxidase activity and pro-inflammatory cytokine levels in LPS-induced ALI mice. RESULTS:Amphipathic GLP-1 interacted spontaneously with SSM as indicated by increased α-helicity and fluorescence emission. This association elicited increased bioactivity as determined by in vitro cAMP production. Correspondingly, subcutaneous GLP1-SSM (5-30 nmol/mouse) manifested dose-dependent decrease in lung neutrophil influx, myeloperoxidase activity and interleukin-6 in ALI mice. By contrast, GLP-1 in saline showed no significant anti-inflammatory effects against LPS-induced lung hyper-inflammatory responses. CONCLUSIONS:GLP1-SSM is a promising novel anti-inflammatory nanomedicine against ALI and should be further developed for its transition to clinics.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Lim SB,Rubinstein I,Sadikot RT,Artwohl JE,Önyüksel Hdoi
10.1007/s11095-010-0322-4subject
Has Abstractpub_date
2011-03-01 00:00:00pages
662-72issue
3eissn
0724-8741issn
1573-904Xjournal_volume
28pub_type
杂志文章abstract：PURPOSE:To examine whether the glass transition temperature (Tg) of freeze-dried formulations containing polymer excipients can be accurately predicted by molecular dynamics simulation using software currently available on the market. Molecular dynamics simulations were carried out for isomaltodecaose, a fragment of de...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1023831102203
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abstract：PURPOSE:A theory and computer programs running on Microsoft Excel for Windows for calculation of solution pH, buffer formula, and buffer capacity at a given ionic strength and temperature were developed. The theory does not limit the category of buffer components, the number of buffer components, or the number of ioniz...
journal_title：Pharmaceutical research
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abstract：PURPOSE:The passage of molecules across cell membranes is a crucial step in many physiological processes. We therefore seek physical models of this process, in order to predict permeation for new molecules, and to better understand the important interactions which determine the rate of permeation. METHODS:Several sets...
journal_title：Pharmaceutical research
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abstract：PURPOSE:The purpose of this study was to assess the antifungal activity and renal and hepatic toxicity of amphotericin B (AmpB) following administration of Fungizone (FZ) and a heat-treated form of FZ (HFZ) to rats infected with Aspergillus fumigatus. METHODS:Infected rats were administered FZ and HFZ at a dosing regi...
journal_title：Pharmaceutical research
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doi：10.1023/b:pham.0000041449.46054.b4
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abstract：PURPOSE:Due to protease inhibitor (PI) efflux transport by P-glycoprotein (P-gp), insufficient PI concentrations result in low ongoing HIV replication in the so-called virus sanctuaries (brain and testes). The aim of the present study was to evaluate indinavir-loaded nanocapsules (Ind-LNC) including Solutol HS15, an ex...
journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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doi：10.1023/a:1015847103862
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1013370529366
更新日期：2001-12-01 00:00:00
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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更新日期：2021-01-06 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015866714224
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journal_title：Pharmaceutical research
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更新日期：1991-08-01 00:00:00
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journal_title：Pharmaceutical research
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doi：10.1007/s11095-015-1629-y
更新日期：2015-07-01 00:00:00
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更新日期：2019-02-22 00:00:00
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更新日期：2019-12-26 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011094025008
更新日期：2001-04-01 00:00:00
abstract：:Silk is a remarkable biopolymer with a long history of medical use. Silk fabrications have a robust track record for load-bearing applications, including surgical threads and meshes, which are clinically approved for use in humans. The progression of top-down and bottom-up engineering approaches using silk as the basi...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
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更新日期：2018-11-05 00:00:00
abstract：PURPOSE:This study was designed to investigate the stability of recombinant FVIII (rFVIII) in solution at different pHs and to probe the cause(s) of rFVIII inactivation under accelerated storage conditions. METHODS:Aqueous stability samples of full-length rFVIII at different pHs were incubated at 40 degrees C for seve...
journal_title：Pharmaceutical research
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更新日期：2003-04-01 00:00:00
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journal_title：Pharmaceutical research
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doi：10.1023/a:1020492213172
更新日期：2002-10-01 00:00:00
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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更新日期：2017-03-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016438413297
更新日期：1987-10-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018868423309
更新日期：1999-05-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0788-3
更新日期：2012-09-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018989211864
更新日期：1999-08-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1469-1
更新日期：2015-02-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018962415287
更新日期：1994-04-01 00:00:00
abstract：PURPOSE:Basal insulins with improved kinetic properties can potentially be produced using acylation by fatty acids that enable soluble, high-molecular weight complexes to form post-injection. A series of insulins, acylated at B29 with fatty acids via glutamic acid spacers, were examined to deduce the structural require...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0739-z
更新日期：2012-08-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-8498-8
更新日期：2006-01-01 00:00:00
