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载聚多巴胺脂质体:稳定的纳米制剂、均匀的涂层和优异的抗污染性能。

Polydopamine-on-liposomes: stable nanoformulations, uniform coatings and superior antifouling performance.

机构信息

Department of Chemistry, Indian Institute of Science Education and Research, Bhauri, Bhopal By-pass Road, Bhopal-462066, India.

Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurugram Expressway, Faridabad-121001, Haryana, India.

出版信息

Nanoscale. 2020 Feb 27;12(8):5021-5030. doi: 10.1039/c9nr07770g.

Abstract

Polydopamine (PDA), a mussel-inspired synthetic polymer, affords biocompatible and antifouling coatings on a variety of surfaces. However, the traditional protocol of preparing PDA by polymerizing dopamine (DA) under basic conditions yields physically-unstable and non-uniform coatings that are prone to delamination and exhibit compromised antifouling performance in vivo. Here, we show that the high local pH in the vicinity of vesicular self-assemblies formed by a series of acetal-based cationic amphiphiles can be exploited to conveniently polymerise DA under physiological conditions in a gradual manner without requiring any external oxidant. Two of the four PDA-liposome nanoformulations viz. PDA-L1 and PDA-L2 turned out to be highly stable physically and resisted precipitation for more than a month while the other two formulations (PDA-L3 and PDA-L4) were less stable and formed visible precipitates with time. Further, the PDA-liposome formulations had significantly improved haemocompatibility compared to that of pristine liposomes. PDA-L1 formed highly uniform, nanostructured coatings on implants like catheter, cotton and bandages that did not delaminate even after a week of continuous incubation in simulated body fluid, or on exposure to pH change and presence of proteolytic enzymes. The PDA-L1 coated catheter implants resisted biofouling by both Gram-positive and Gram-negative bacteria in vitro and also had superior in vivo performance in mice vis-à-vis the implants coated with traditional base-polymerised PDA formulation (BP-PDA). Thus, these novel liposomal PDA nanoformulations significantly improve the practical utility of PDA-based coatings for antimicrobial applications.

摘要

聚多巴胺(PDA)是一种受贻贝启发的合成聚合物,可在各种表面上提供生物相容且抗污的涂层。然而,通过在碱性条件下聚合多巴胺(DA)来制备 PDA 的传统方法会产生物理不稳定且不均匀的涂层,容易分层,并在体内表现出受损的抗污性能。在这里,我们表明,一系列基于缩醛的阳离子两亲分子形成的囊泡自组装体附近的高局部 pH 值可用于在生理条件下以逐渐的方式方便地聚合 DA,而无需任何外部氧化剂。四种 PDA-脂质体纳米制剂中的两种,即 PDA-L1 和 PDA-L2,结果证明在物理上非常稳定,并且能够抵抗沉淀超过一个月,而另外两种制剂(PDA-L3 和 PDA-L4)则不太稳定,并且随着时间的推移会形成可见的沉淀。此外,与原始脂质体相比,PDA-脂质体制剂具有显著改善的血液相容性。PDA-L1 在导管、棉花和绷带等植入物上形成了高度均匀的纳米结构涂层,即使在模拟体液中连续孵育一周后也不会分层,或者在 pH 值变化和存在蛋白水解酶的情况下也不会分层。PDA-L1 涂层的导管植入物在体外抵抗革兰氏阳性菌和革兰氏阴性菌的生物污染,并且在体内与用传统的碱基聚合 PDA 制剂(BP-PDA)涂层的植入物相比具有更好的性能。因此,这些新型的脂质体 PDA 纳米制剂显著提高了基于 PDA 的涂层在抗菌应用中的实际效用。

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