Abstract：
:Bone fractures constitute a major cause of morbidity and mortality especially in the elderly. Complications associated with osteoporosis drugs and the age of the patient slow bone turnover and render such fractures difficult to heal. Increasing the speed of fracture repair by administration of a fracture-targeted bone anabolic agent could find considerable application. Aspartic acid oligopeptides are negatively charged molecules at physiological pH that adsorb to hydroxyapatite, the mineral portion of bone. This general adsorption is the strongest where bone turnover is highest or where hydroxyapatite is freshly exposed. Importantly, both of these conditions are prominent at fracture sites. GSK3β inhibitors are potent anabolic agents that can promote tissue repair when concentrated in a damaged tissue. Unfortunately, they can also cause significant toxicity when administered systemically and are furthermore difficult to deliver due to their strong hydrophobicity. In this paper, we solve both problems by conjugating the hydrophobic GSK3β inhibitor to a hydrophilic aspartic acid octapeptide using a hydrolyzable bond, thereby generating a bone fracture-targeted water-soluble form of the drug. The resulting amphiphile is shown to assemble into micelles, extending its circulation time while maintaining its fracture-targeting abilities. For measurement of pharmacokinetics, an 125I was introduced at the location of the bromine in the GSK3β inhibitor to minimize any structural differences. Biodistribution studies demonstrate a greater than 4-fold increase in fracture accumulation over healthy bone.
journal_name
Biomacromoleculesjournal_title
Biomacromoleculesauthors
Low SA,Galliford CV,Yang J,Low PS,Kopeček Jdoi
10.1021/acs.biomac.5b00777subject
Has Abstractpub_date
2015-10-12 00:00:00pages
3145-53issue
10eissn
1525-7797issn
1526-4602journal_volume
16pub_type
杂志文章abstract：:This paper reports the rheological behavior of chitosan solutions that have been cross-linked with different amounts of genipin, at body temperature and physiological pH. The effect of the cross-linker loading on the rheological properties of hydrogels has been evaluated. The oscillatory time sweep method was used to ...
journal_title：Biomacromolecules
pub_type： 杂志文章
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journal_title：Biomacromolecules
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doi：10.1021/bm020131n
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journal_title：Biomacromolecules
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journal_title：Biomacromolecules
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journal_title：Biomacromolecules
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journal_title：Biomacromolecules
pub_type： 杂志文章
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journal_title：Biomacromolecules
pub_type： 杂志文章,评审
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更新日期：2005-03-01 00:00:00
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journal_title：Biomacromolecules
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pub_type： 杂志文章
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更新日期：2004-09-01 00:00:00
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journal_title：Biomacromolecules
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doi：10.1021/bm400680d
更新日期：2013-08-12 00:00:00
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journal_title：Biomacromolecules
pub_type： 杂志文章
doi：10.1021/bm070289d
更新日期：2007-09-01 00:00:00
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journal_title：Biomacromolecules
pub_type： 杂志文章
doi：10.1021/bm1006954
更新日期：2010-12-13 00:00:00
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journal_title：Biomacromolecules
pub_type： 杂志文章
doi：10.1021/bm2009312
更新日期：2011-09-12 00:00:00
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journal_title：Biomacromolecules
pub_type： 杂志文章
doi：10.1021/bm015586b
更新日期：2002-01-01 00:00:00
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journal_title：Biomacromolecules
pub_type： 杂志文章
doi：10.1021/bm301481v
更新日期：2012-12-10 00:00:00
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journal_title：Biomacromolecules
pub_type： 杂志文章
doi：10.1021/acs.biomac.8b01084
更新日期：2018-10-08 00:00:00
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journal_title：Biomacromolecules
pub_type： 杂志文章
doi：10.1021/bm049325o
更新日期：2005-01-01 00:00:00
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journal_title：Biomacromolecules
pub_type： 杂志文章
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更新日期：2020-02-10 00:00:00
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journal_title：Biomacromolecules
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更新日期：2008-04-01 00:00:00
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journal_title：Biomacromolecules
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更新日期：2001-10-01 00:00:00
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journal_title：Biomacromolecules
pub_type： 杂志文章
doi：10.1021/bm015531+
更新日期：2001-10-01 00:00:00
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journal_title：Biomacromolecules
pub_type： 杂志文章
doi：10.1021/bm400022h
更新日期：2013-05-13 00:00:00
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journal_title：Biomacromolecules
pub_type： 杂志文章
doi：10.1021/acs.biomac.5b01252
更新日期：2016-01-11 00:00:00
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journal_title：Biomacromolecules
pub_type： 杂志文章,评审
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journal_title：Biomacromolecules
pub_type： 杂志文章
doi：10.1021/bm060927c
更新日期：2007-02-01 00:00:00
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journal_title：Biomacromolecules
pub_type： 杂志文章
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更新日期：2018-06-11 00:00:00
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journal_title：Biomacromolecules
pub_type： 杂志文章
doi：10.1021/acs.biomac.7b00927
更新日期：2017-10-09 00:00:00
