Cisplatin encapsulated in phosphatidylethanolamine liposomes enhances the in vitro cytotoxicity and in vivo intratumor drug accumulation against melanomas.
BACKGROUND
Cisplatin is a potent anticancer drug for treating melanoma.


OBJECTIVE
The aim of this study was to evaluate the possibility of using liposomes, for intratumoral distribution in a melanoma, composed of phosphatidylethanolamine (PE), for its cytotoxicity.


METHODS
The in vitro drug release, in vitro cytotoxicity against melanoma, and in vivo residence time in the tumor of liposome-encapsulated cisplatin were investigated. The liposomes were prepared and characterized in terms of their morphology, size, zeta potential, and drug loading.


RESULTS
The size of the PE liposomes attained a level of approximately 100 nm. The concentration of cisplatin encapsulated in PE liposomes was 50-70% dependent on the presence or absence of polyethylene glycol (PEG) derivatives. On the other hand, no or negligible cisplatin molecules were encapsulated in egg phosphatidylcholine (EPC) liposomes. PE liposomes had higher cytotoxicity than classic liposomes or free cisplatin. Images of confocal laser scanning microscopy confirmed the great potency of PE liposomes to deliver cisplatin into cells. The incorporation of PEG derivatives completely inhibited the proliferation of melanoma cells. With in vivo intratumoral administration, the cisplatin concentration in the tumor tissue was maintained at a high level for 72 h after application of the PE liposomes. The PE liposomes delivered cisplatin into the tumor approximately 3.6 times more efficiently than the free drug.


CONCLUSIONS
These results demonstrate that PE liposomes represent a potentially useful strategy for targeting cisplatin delivery into melanomas.
Hwang
Tsong-Long
TL
Cell Pharmacology Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Lee
Woan-Ruoh
WR
Hua
Shu-Chiou
SC
Fang
Jia-You
JY
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000493:pharmacokinetics* / Q000633:toxicity; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015552:Injections, Intralesional; D008081:Liposomes / Q000493:pharmacokinetics*; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D010714:Phosphatidylethanolamines / Q000493:pharmacokinetics; D012878:Skin Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D008081:Liposomes; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; D002945:Cisplatin