Yang Yu-Tsai, Chien Hsiung-Fei, Chang Po-Han, Chen Yee-Chun, Jay Michael, Tsai Tsuimin, Chen Chin-Tin
Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
Lasers Surg Med. 2013 Mar;45(3):175-85. doi: 10.1002/lsm.22124.
Antimicrobial photodynamic inactivation (PDI) is a promising therapeutic modality for the treatment of local infections. To increase the efficacy of PDI, chlorine e6 (Ce6) was encapsulated in cationic CTAB-liposomes composed of various ratios of dimyristoyl-sn-glycero-phosphatidylcholine (DMPC) and the cationic surfactant, cetyltrimethyl ammonium bromide (CTAB). The PDI efficacy of the liposomal-Ce6 was assessed in vitro against susceptible and drug-resistant clinical isolates of Candida albicans (C. albicans) as well as in infected burn wounds.
STUDY DESIGN/MATERIALS AND METHODS: Ce6 was encapsulated in CTAB-liposomes by the film hydration method. Particle size distribution and zeta potential of the cationic liposomes were measured using a Zetasizer Nano-ZS. UV-visible spectra were used to measure lipid/Ce6 (L/C) ratio and drug entrapment efficiency while differential scanning calorimetry (DSC) was used to study the thermotropic behavior of DMPC liposomes upon CTAB addition. In vivo PDI efficacy was carried out in an infected burn wound using a rat model.
The increase in zeta potential and a shift in the phase transition temperature (Tm ) upon CTAB addition confirmed its entrapment within the lipid bilayers of the liposome. Meanwhile, the CTAB addition did not affect the Ce6 entrapment efficiency and physical attributes of the liposomes. In vitro studies showed that the PDI effect of the Ce6-loaded CTAB-liposomes was dependent on the lipid to Ce6 molar ratio (L/C), particle size and the concentration of CTAB in the liposomes. The lower L/C ratio and smaller liposomes exerted significantly higher PDI effects. In addition, an increase in the CTAB to lipid ratio led to a significant increase in the PDI effect of Ce6 against susceptible and drug-resistant clinical isolates of C. albicans after light illumination.
Our results indicate that a low L/C ratio, high positive charge, and small particle size of CTAB-liposomes significantly enhances their PDI efficacy against C. albicans.
抗菌光动力灭活（PDI）是一种治疗局部感染的有前景的治疗方式。为提高PDI的疗效，将氯e6（Ce6）包裹于由不同比例的二肉豆蔻酰-sn-甘油磷脂酰胆碱（DMPC）和阳离子表面活性剂十六烷基三甲基溴化铵（CTAB）组成的阳离子CTAB脂质体中。评估了脂质体-Ce6在体外对白色念珠菌（白假丝酵母菌）的敏感和耐药临床分离株以及在感染烧伤创面的PDI疗效。
研究设计/材料与方法：通过薄膜水化法将Ce6包裹于CTAB脂质体中。使用Zetasizer Nano-ZS测量阳离子脂质体的粒径分布和zeta电位。紫外可见光谱用于测量脂质/Ce6（L/C）比和药物包封率，而差示扫描量热法（DSC）用于研究添加CTAB后DMPC脂质体的热致行为。使用大鼠模型在感染烧伤创面进行体内PDI疗效研究。
添加CTAB后zeta电位升高以及相变温度（Tm）的变化证实其被包裹于脂质体的脂质双层内。同时，添加CTAB不影响Ce6的包封率和脂质体的物理性质。体外研究表明，负载Ce6的CTAB脂质体的PDI效应取决于脂质与Ce6的摩尔比（L/C）、粒径以及脂质体中CTAB的浓度。较低的L/C比和较小的脂质体具有显著更高的PDI效应。此外，CTAB与脂质比的增加导致光照后Ce6对白色念珠菌的敏感和耐药临床分离株的PDI效应显著增加。
我们的结果表明，低L/C比、高正电荷和小粒径的CTAB脂质体显著增强了它们对白假丝酵母菌的PDI疗效。
