期刊
BIOMACROMOLECULES
卷 22, 期 12, 页码 5185-5194出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.1c01133
关键词
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资金
- ARC Future Fellowship Scheme [FT150100408]
- National Health and Medical Research Council (NHMRC) Project grant [GNT1144046]
- FWO Flanders
- Ghent University
The polymer-antibiotic conjugate has thermoresponsive properties near body temperature, allowing for localized antibiotic delivery and efficient clearance of Escherichia coli within 12 hours.
A polymer-antibiotic conjugate with thermoresponsive properties near body temperature is presented. The backbone polymer is a copolymer of 2-n-propyl-2-oxazine (PropOzi) and methoxycarbonylethyl-2-oxazoline (C(2)MestOx) which is conjugated with the broad-spectrum antibiotic, cefazolin, via modification of the methyl ester group of C(2)MestOx. The resulting polymer-antibiotic conjugate has a cloud point temperature near body temperature, meaning that it can form a homogenous solution if cooled, but when injected into a skin-mimic at 37 degrees C, it forms a drug depot precipitate. Cleavage of the ester linker leads to quantitative release of the pristine cefazolin (with some antibiotic degradation observed) and redissolution of the polymer. When Escherichia coli were treated with polymer-antibiotic conjugate total clearance is observed within 12 h. The power of this approach is the potential for localized antibiotic delivery, for example, at a specific tissue site or into infected phagocytic cells.
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