Low level LED photodynamic therapy using curcumin loaded tetraether liposomes

被引:64
作者
Duse, Lili [1 ]
Pinnapireddy, Shashank Reddy [1 ]
Strehlow, Boris [1 ]
Jedelska, Jarmila [1 ]
Bakowsky, Udo [1 ]
机构
[1] Univ Marburg, Dept Pharmaceut & Biopharmaceut, D-35037 Marburg, Germany
关键词
Photodynamic therapy; LED; Curcumin; Tetraether liposomes; Cancer; Chorioallantoic membrane; Serum stability; CHORIOALLANTOIC MEMBRANE MODEL; NANOPARTICLE; APOPTOSIS; STABILITY;
D O I
10.1016/j.ejpb.2017.10.005
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Ontological use of photodynamic therapy is an evolving field in cancer therapeutics. Photosensitisers are prone to accumulation inside healthy tissues causing undesirable effects. To avoid this, we have developed tetraether lipid liposomal formulations containing curcumin which is a naturally occurring anti-cancer substance and deemed to be safe towards healthy cells. Upon excitation with light at a specific wavelength, curcumin produces reactive oxygen species (ROS) in presence of oxygen, thereby exhibiting a cytotoxic effect towards the surrounding tissues, giving a total control on the onset of therapy. In our study, we examined two different liposomal formulations wherein curcumin is encapsulated within the hydrophobic milieu with the intent to increase its bioavailability. Hydrodynamic diameter, surface charge, stability, morphology and haemocompatibility of the liposomes were studied. The results confirmed the formation of stable nanometre range liposomal vesicles (200-220 nm) containing curcumin which were haemocompatible with coagulation time less than 50 s and a haemolytic potential below 40%. Increased ROS generation post irradiation (> 50% compared to un-irradiated samples) was confirmed using fluorescence spectroscopy. The efficiency and selectivity of the PDT was demonstrated by assessing their viability post irradiation and by qualitative analysis using confocal microscopy showing nuclear perforation induced by PDT. Photo -destructive effects of PDT on the microvasculature were studied in vivo using chick chorioallantoic membrane model (CAM). Considerable phototoxicity could be observed in the irradiated area of the CAM 30 min post irradiation. Phototoxic effects in vitro (in SK-OV-3 and PCS100-020 (TM)) and in vivo (in chorioallantoic membrane model) in combination with a novel custom manufactured LED irradiating device showed a formulation dependant selective photodynamic effect of the curcumin liposomes.
引用
收藏
页码:233 / 241
页数:9
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