一种合成的、热敏反应的聚合物，聚(N-异丙基丙烯酰胺)-共-(聚乳酸/2-羟基甲基丙烯酸酯)-共-(寡聚(乙二醇))，被用于制备一种持续释放药物的通用载体平台。所谓的TP载体是通过在相对中性pH的水溶液中溶解聚合物而制备的。此载体可以容纳多种治疗物质而无需添加表面活性剂、有机溶剂和其他试剂。制备出的溶液可以通过细针流动，从而实现精确地将TP注射到目标部位。注射后，TP载体会发生从螺旋到球形的相变，形成一个水凝胶矩阵在位。聚合物载体的良性性质和其物理胶凝过程对于保留包埋化合物的生物活性至关重要，而基质的粘合水凝胶性质则允许所载药物的持续释放和控制性的递送。已进行多项体外研究证明，TP载体系统具有无毒和少量炎症反应的特点。这些发现表明，TP可以作为治疗物质的启动载体，用于局部和持续的药物递送。为了确认这一假设，评估了TP封装和有效递送具有不同理化特性的多种治疗物质的能力。具体来说，测试了包括氯霉素HCl、肿瘤坏死因子α(TNF-α)、转化生长因子β1(TGF-β1)和重组人骨形态发生蛋白2(BMP2)在内的多种化合物。体外研究证实，无论所载药物的理化物性如何，TP载体都能够在较长时间内控制药物的释放并减轻其突发释放。重要的是，体内外动物研究表明，从TP水凝胶基质释放出的药物仍然具有强效和生物活性，这证实了TP聚合物系统作为一种启动载体的高潜力。版权所有©2023，由Elsevier B.V.出版。

A synthetic and thermo-responsive polymer, poly(N-isopropylacrylamide)-co-(polylactide/2-hydroxy methacrylate)-co-(oligo (ethylene glycol)), is used to formulate a universal carrier platform for sustained drug release. The enabling carrier, denoted as TP, is prepared by dissolving the polymer in an aqueous solution at a relatively neutral pH. A wide range of therapeutic moieties can be incorporated without the need for the addition of surfactants, organic solvents, and other reagents to the carrier system. The resulting solution is flowable through fine gauge needle, allowing accurate administration of TP to the target site. After injection, TP carrier undergoes a coil to globe phase transition to form a hydrogel matrix at the site. The benign nature of the polymer carrier and its physical gelation process are essential to preserve the biological activity of the encapsulated compounds while the adhesive hydrogel nature of the matrix allows sustained elusion and controlled delivery of the incorporated therapeutics. The TP carrier system has been shown to be non-toxic and elicits a minimal inflammatory response in multiple in vitro studies. These findings suggest the suitability of TP as an enabling carrier of therapeutics for localized and sustained drug delivery. To confirm this hypothesis, the capabilities of TP to encapsulate and effectively deliver multiple therapeutics of different physicochemical characteristics was evaluated. Specifically, a broad range of compounds were tested, including ciprofloxacin HCl, tumor necrosis factor-alpha (TNF-α), transforming growth factor beta 1 (TGF-β1), and recombinant human bone morphogenetic protein 2 (BMP2). In vitro studies confirmed that TP carrier is able to control the release of the encapsulated drugs over an extended period of time and mitigate their burst release regardless of the compounds' physiochemical properties for the majority of the loaded therapeutics. Importantly, in vitro and in vivo animal studies showed that the released drugs from the TP hydrogel matrix remained potent and bioactive, confirming the high potential of the TP polymer system as an enabling carrier.Copyright © 2023. Published by Elsevier B.V.