Department of Pharmaceutical Technology, Friedrich-Schiller-University Jena, Jena, Germany.
Photochem Photobiol. 2012 May-Jun;88(3):548-56. doi: 10.1111/j.1751-1097.2011.00983.x. Epub 2011 Sep 16.
Photodynamic inactivation (PDI) of bacteria is a promising approach for combating the increasing emergence of antibiotic resistance in pathogenic bacteria. To further improve the PDI efficiency on bacteria, a bacteria-targeting liposomal formulation was investigated. A generation II photosensitizer (temoporfin) was incorporated into liposomes, followed by conjugation with a specific lectin (wheat germ agglutinin, WGA) on the liposomal surface. WGA was successfully coupled to temoporfin-loaded liposomes using an activated phospholipid containing N-hydroxylsuccinimide residue. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were selected to evaluate the WGA modified liposomes in terms of bacteria targeted delivery and in vitro PDI test. Fluorescence microscopy revealed that temoporfin was delivered to both kinds of bacteria, while flow cytometry demonstrated that WGA- modified liposomes delivered more temoporfin to bacteria compared to nonmodified liposomes. Consequently, the WGA- modified liposomes eradicated all MRSA and significantly enhanced the PDI of P. aeruginosa. In conclusion, the WGA- modified liposomes are a promising formulation for bacteria targeted delivery of temoporfin and for improving the PDI efficiency of temoporfin on both Gram-positive and Gram-negative bacterial cells.
光动力失活（PDI）细菌是一种有前途的方法，可用于对抗致病菌中抗生素耐药性的日益出现。为了进一步提高细菌的 PDI 效率，研究了一种细菌靶向脂质体制剂。将第二代光敏剂（替莫泊芬）掺入脂质体中，然后在脂质体表面与特定的凝集素（麦胚凝集素，WGA）缀合。使用含有 N-羟基琥珀酰亚胺残基的活化磷脂成功地将 WGA 偶联到载有替莫泊芬的脂质体上。选择耐甲氧西林金黄色葡萄球菌（MRSA）和铜绿假单胞菌来评估 WGA 修饰的脂质体在细菌靶向递送上的效果和体外 PDI 测试。荧光显微镜显示替莫泊芬被递送到两种细菌中，而流式细胞术表明与非修饰脂质体相比，WGA 修饰的脂质体向细菌递送了更多的替莫泊芬。因此，WGA 修饰的脂质体根除了所有的 MRSA 并显著增强了 P. aeruginosa 的 PDI。总之，WGA 修饰的脂质体是一种有前途的替莫泊芬靶向递药制剂，可提高替莫泊芬对革兰氏阳性和革兰氏阴性细菌细胞的 PDI 效率。
