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基于泊洛沙姆的水凝胶作为药物递送系统:聚合物辅料如何影响化学物理性质。

Poloxamer-Based Hydrogel as Drug Delivery System: How Polymeric Excipients Influence the Chemical-Physical Properties.

作者信息

Brambilla Elisa, Locarno Silvia, Gallo Salvatore, Orsini Francesco, Pini Carolina, Farronato Marco, Thomaz Douglas Vieira, Lenardi Cristina, Piazzoni Marco, Tartaglia Gianluca

机构信息

Department of Pharmaceutical Sciences, Section of General and Organic Chemistry Section "A. Marchesini", University of Milan, 20133 Milan, Italy.

Department of Physics "Aldo Pontremoli", University of Milan, 20133 Milan, Italy.

出版信息

Polymers (Basel). 2022 Sep 1;14(17):3624. doi: 10.3390/polym14173624.

Abstract

Thermogelling amphiphilic block copolymers have been widely investigated in the development of pharmaceutical drug carriers. In particular, thermosensitive gels based on poloxamer 407 (P407) have great potential for periodontal disease treatment, thanks to their ability to be liquid at room temperature and become viscous gels at body temperature. However, some problems, related to short in situ residence time, reduce their feasible clinical use. Thus, in order to improve the effective applicability of these materials, we studied how P407 thermogels are affected by the pH and by the inclusion of different hydrophilic polymers, used as excipients for increasing the gel stiffness. For this scope, a complete chemical-physical characterization of the synthesized gels is provided, in terms of determination of sol-gel transition temperature, viscosity and erosion degree. The data are correlated according to a statistical multivariate approach based on Principal Component Analysis and their mucoadhesion properties are also tested by Tapping mode-Atomic Force Microscopy (TM-AFM) imaging. Finally, we studied how the different P407 formulations are able to influence the release pathway of two antibacterial drugs (i.e., chlorhexidine digluconate and doxycycline hyclate) largely used in oral diseases.

摘要

温敏性两亲嵌段共聚物在药物载体开发中已得到广泛研究。特别是基于泊洛沙姆407(P407)的热敏凝胶在牙周疾病治疗方面具有巨大潜力,这得益于其在室温下呈液态而在体温下变为粘性凝胶的特性。然而,一些与原位停留时间短相关的问题限制了它们在临床上的实际应用。因此,为了提高这些材料的有效适用性,我们研究了P407热敏凝胶如何受到pH值以及不同亲水性聚合物添加的影响,这些亲水性聚合物用作增加凝胶硬度的辅料。为此,我们对合成凝胶进行了全面的化学物理表征,包括测定溶胶-凝胶转变温度、粘度和侵蚀程度。数据通过基于主成分分析的统计多变量方法进行关联,并且还通过敲击模式原子力显微镜(TM-AFM)成像测试了它们的粘膜粘附特性。最后,我们研究了不同的P407配方如何影响两种在口腔疾病中广泛使用的抗菌药物(即葡萄糖酸氯己定和盐酸多西环素)的释放途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c28/9460339/ff2333f04807/polymers-14-03624-g001.jpg

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