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Park, Jong Ryul
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article
Thermoresponsive Polymer-Antibiotic Conjugates Based on Gradient Copolymers of 2-Oxazoline and 2-Oxazine
Abstract
<p class="articleBody_abstractText">A polymer–antibiotic conjugate withthermoresponsive properties near body temperature is presented. Thebackbone polymer is a copolymer of 2-<i>n</i>-propyl-2-oxazine (PropOzi) and methoxycarbonylethyl-2-oxazoline (C<sub>2</sub>MestOx) which is conjugated with the broad-spectrum antibiotic, cefazolin, via modification of the methyl ester group of C<sub>2</sub>MestOx.The resulting polymer–antibiotic conjugate has a cloud pointtemperature near body temperature, meaning that it can form a homogenoussolution if cooled, but when injected into a skin-mimic at 37 °C, itforms a drug depot precipitate. Cleavage of the ester linker leads toquantitative release of the pristine cefazolin (with some antibioticdegradation observed) and redissolution of the polymer. When <i>Escherichia coli</i>were treated with polymer–antibiotic conjugate total clearance isobserved within 12 h. The power of this approach is the potential forlocalized antibiotic delivery, for example, at a specific tissue site orinto infected phagocytic cells.</p>