Preparation And Antibacterial Effects Of Carboxymethyl Chitosan-Modified Photo-Responsive Camellia Sapogenin Derivative Cationic Liposomes
Preparation And Antibacterial Effects Of Carboxymethyl Chitosan-Modified Photo-Responsive Camellia Sapogenin Derivative Cationic Liposomes
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DOI：
10.2147/ijn.s218101
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发表时间：
2019-01-01
影响因子：
8
通讯作者：
Ye, Yong
中科院分区：
文献类型：
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作者：
Zhang, Jin;Ye, Chuan-Zhen;Ye, Yong
背景：细菌对抗生素的耐药性是一个长期而棘手的问题。从油茶籽中分离得到的皂苷元经结构修饰后具有抑制耐药菌的作用，目的：利用光响应性纳米制剂提高皂苷元的抗菌活性，避免细菌耐药。方法：采用酰胺化反应制备了羧甲基壳聚糖-磷脂酰乙醇胺（CMC-PE）脂质体壳材料，和光敏剂脱镁叶绿酸-a的光响应性阳离子脂质体（PCC）。采用高效液相色谱法、粒度分析仪、透射电镜（TEM）、荧光显微镜等对PCC脂质体的包封率、载药量、zeta电位、粒径分布、形态及稳定性进行了测定。通过在665 nm处的激光（0.5mW/cm（2））测定PCC脂质体中CSD的光响应性释放。通过MIC 50、MBC、MBIC 50、细菌形态学等方法评价PCC脂质体对耐阿莫西林大肠杆菌和金黄色葡萄球菌的抑菌作用。结果：PCC脂质体的大小分布、ζ电位、包封率和药物负载分别为189.23 ± 2.12nm、18.80 ± 1.57mV分别为83.52 ± 1.53%和2.83 ± 0.05%。PCC脂质体具有较好的储存稳定性和胃肠道稳定性，对兔红细胞无明显溶血毒性，与Hela细胞共孵育后无细胞毒性。光敏剂脱镁叶绿酸-a均匀分散在PCC脂质体的磷脂层中，并增加了光照后CSD的释放。PCC脂质体能与细菌结合，破坏细菌的形态结构，对耐阿莫西林大肠杆菌有明显的杀菌作用。coli和革兰氏阳性菌S.结论：光响应性PCC脂质体是一种有效的抗菌药物，可避免细菌对抗生素的耐药性。
Background: Bacterial resistance to antibiotics is a persistent and intractable problem. The sapogenin isolated from the seeds of Camellia oleifera can inhibit antibiotic-resistant bacteria after structural modification.Purpose: This study aims to improve sapogenin's antibacterial activity and avoid bacterial resistance based on nano-preparation with photo responsiveness.Methods: The liposome shell material of carboxymethyl chitosan-phosphatidyl ethanolamine (CMC-PE) was prepared using amidation reaction, and photo-responsive cationic (PCC) liposomes containing Camellia sapogenin derivative (CSD) and photosensitizer pheophorbide-a were prepared by film dispersion method. Encapsulation efficiency, drug loading, zeta potential, particle size distribution, morphology and stability of the PCC liposomes were determined by HPLC, particle size analyzer, transmission electron microscopy (TEM) and fluorescence microscopy. Photo-responsive release of CSD in the PCC liposomes was determined by laser (0.5 mW/cm(2)) at 665 nm. Antibacterial activity of the PCC liposomes with or without irradiation was analyzed by MIC50, MBC, MBIC50, and bacterial morphology to evaluate the antibacterial effects on amoxicillin resistant Escherichia coli and Staphylococcus aureus.Results: Size distribution, zeta potential, encapsulation efficiency and drug loading of the PCC liposomes were 189.23 +/- 2.12 nm, 18.80 +/- 1.57 mV, 83.52 +/- 1.53% and 2.83 +/- 0.05%, respectively. The PCC liposomes had higher storage stability and gastrointestinal stability, and no obvious hemolytic toxicity to rabbit red blood cells and no cytotoxicity after incubation with Hela cells. The photosensitizer pheophorbide-a was uniformly dispersed in the phospholipid layer of the PCC liposomes and increased the CSD release after irradiation. The PCC liposomes could bind to bacteria and impaired their morphology and structure, and had significant bactericidal effect on amoxicillin resistant E. coli and S. aureus.Conclusion: The photo-responsive PCC liposomes are efficient antibacterial agents for avoidance of bacterial resistance against antibiotics.