文献：On-demand pH-sensitive surface charge-switchable polymeric micelles for targeting Pseudomonas aeruginosa bioflms development

文献链接：

作者：Xiangjun Chen, Rong Guo, Changrong Wang, Keke Li, Xinyu Jiang, Huayu He and Wei Hong

相关产品：PLA5K-PEI2K-mPEG5K（聚乳酸5k-聚醚酰亚胺2k-甲氧基聚乙二醇5k）

PLA5K-PEI2K-hyd-mPEG5K（聚乳酸5k-聚醚酰亚胺2k-hyd-甲氧基聚乙二醇5k）

原文摘要：

Bacterial bioflm is the complicated clinical issues, which usually results in bacterial resistance and reduce the therapeutic efcacy of antibiotics. Although micelles have been drawn attention in treatment of the bioflms, the micelles efectively permeate and retain in bioflms still facing a big challenge. In this study, we fabricated on-demand pHsensitive surface charge-switchable azithromycin (AZM)-encapsulated micelles (denoted as AZM-SCSMs), aiming to

act as therapeutic agent for treating Pseudomonas aeruginosa (P. aeruginosa) bioflms. The AZM-SCSMs was composed of poly(l-lactide)-polyetherimide-hyd-methoxy polyethylene glycol (PLA-PEI-hyd-mPEG). It was noteworthy that the pH-sensitive acylhydrazone bond could be cleaved in acidic bioflm microenvironment, releasing the secondary AZMloaded cationic micelles based on PLA-PEI (AZM-SCMs) without destroying the micellar integrity, which could tailor drug-bacterium interaction using micelles through electrostatic attraction. The results proved that positively charged AZM-SCMs could facilitate the enhanced penetration and retention inside bioflms, improved binding afnity with bacterial membrane, and added drug internalization, thus characterized as potential anti-bioflm agent. The excellent in vivo therapeutic performance of AZM-SCSMs was confrmed by the targeting delivery to the infected tissue and reduced bacterial burden in the abscess-bearing mice model. This study not only developed a novel method for construction non-depolymerized pH-sensitive SCSMs, but also provided an efective means for the treatment of bioflm-related infections.

 PLA5K-PEI2K-mPEG5K: PLA 是聚乳酸，它是一种生物可降解的热塑性聚酯。聚乳酸具有良好的生物相容性、机械性能和加工性能。PEI 是聚醚酰亚胺，这是一种高性能的热塑性工程塑料。它具有耐高温、高强度、高模量等良好的物理和化学性能。mPEG 是甲氧基聚乙二醇，聚乙二醇具有良好的水溶性、生物相容性和柔顺性，甲氧基聚乙二醇是聚乙二醇的一种衍生物，其一端是甲氧基封端，在化合物传递、生物医学等领域应用广。

PLA5K-PEI2K-hyd-mPEG5K:PLA 是聚乳酸，一种生物可降解的热塑性聚酯。 5K表示其分子量大小，意味着该聚乳酸的分子量大概为 5000。聚乳酸有良好的生物相容性、机械性能等特点。PEI 指的是聚乙烯亚胺，一种具有高阳离子电荷密度的聚合物，在基因转染、化合物递送等生物医学领域应用较多。2K表示其分子量约为 2000，分子量大小会影响它的溶解性、与其他物质相互作用的能力等性质。mPEG指的是甲氧基聚乙二醇，常被用于对一些化合物、纳米材料等进行修饰，目的是改善其亲水性、稳定性以及减少在体内的免疫原性等。5K表示其分子量大约为 5000，这种聚合物链段接上后可以赋予整个分子更好的水溶性等特点，使其更适合在一些水性环境下应用。基于PLA5K-PEI2K-mPEG5K和PLA5K-PEI2K-hyd-mPEG5K的性能，封装胶束AZM-SCSMs合成如下：

图：合成示意

将PLA-PEI-hydmPEG溶解在二氯甲烷和甲醇的混合溶剂中。通过溶剂的旋转蒸发得到了Te flm。，flm用PBS水合，然后通过flm进行冲洗。除使用PLA-PEI-mPEG作为共聚物外，SCUMs制备的方法相同。通过封装AZM制备了te AZM-SCSMs和AZM-SCUMs。在JEM1400 TEM上研究Te胶束形貌，在Za分析仪上测量了粒径和zeta电位。通过方程式计算载药量（DL%）和诱捕率（EE%）。

图：表征图像

结论：

该文献成功制出基于PLA5K-PEI2K-mPEG5K和PLA5K-PEI2K-hyd-mPEG5K合成的封装胶束AZM-SCSMs。实验表明，SCSMs在不破坏胶束完整性的情况下，实现了电荷逆转。而且，胶束可以保持其完整性，以促进化合物-bacteria的相互作用。AZM-SCSMs在体内和体外均表现出增强的生物膜穿透能力和良好的抗生物膜能力。综上，AZM-SCSMs具有良好的生物膜渗透性和杀菌能力，可用于其他抗菌化合物的传递。