Linked Life Data

17226975

Source:http://linkedlifedata.com/resource/pubmed/id/17226975

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-1-17
pubmed:abstractText
To give the first demonstration of neighboring group-controlled drug delivery rates, a series of novel, polymerizable ester drug conjugates was synthesized and fully characterized. The monomers are suitable for copolymerization in biomaterials where control of drug release rate is critical to prophylaxis or obviation of infection. The incorporation of neighboring group moieties differing in nucleophilicity, geometry, and steric bulk in the conjugates allowed the rate of ester hydrolysis, and hence drug liberation, to be rationally and widely controlled. Solutions (2.5 x 10-5 mol dm-3) of ester conjugates of nalidixic acid incorporating pyridyl, amino, and phenyl neighboring groups hydrolyzed according to first-order kinetics, with rate constants between 3.00 +/- 0.12 x 10-5 s -1 (fastest) and 4.50 +/- 0.31 x 10- 6 s-1 (slowest). The hydrolysis was characterized using UV-visible spectroscopy. When copolymerized with poly(methyl methacrylate), free drug was shown to elute from the resulting materials, with the rate of release being controlled by the nature of the conjugate, as in solution. The controlled molecular architecture demonstrated by this system offers an attractive class of drug conjugate for the delivery of drugs from polymeric biomaterials such as bone cements in terms of both sustained, prolonged drug release and minimization of mechanical compromise as a result of release. We consider these results to be the rationale for the development of "designer" drug release biomaterials, where the rate of required release can be controlled by predetermined molecular architecture.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1043-1802
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
209-15
pubmed:meshHeading
pubmed:articleTitle
Neighboring group-controlled hydrolysis: towards "designer" drug release biomaterials.
pubmed:affiliation
School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK. c.mccoy@qub.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't