Enhancement of Doxorubicin by Encapsulation in Long Circulating Thermosensitive Liposomes Combined with Local Hyperthermia
The therapeutic efficacy of antitumor drugs is restricted by dose-limiting toxicities to normal tissues in vivo, but would be greatly improved if the drugs could be selectively directed to the tumor sites and away from sensitive tissues. Liposomes have been proposed to be useful drug carriers for targeted drug delivery systems, and are under investigation in several therapeutic fields.1,2 In order to achieve maximum targeting, liposomes should remain in the systemic circulation for a long time. However, formulations of liposomes used in the past were rapidly removed from the circulation by the reticuloendothelial system (RES).3,4 It has been demonstrated recently that newly developed liposomes, containing either monosialoganglioside GM, (GM1)S or amphipathic polyethylene glycol (PEG),6–8 are not readily taken up by the macrophages in the RES and hence stay in the circulation for a relatively long period of time. More importantly, these long circulating liposomes, having small size (100–200 nm in mean diameter), showed significantly greater accumulation in solid tumors compared with the corresponding conventional liposomes. 9,10 These reports indicate that long circulating liposomes offer considerable potential for drug targeting to solid tumor.
KeywordsLarge Unilamellar Vesicle Local Hyperthermia Target Drug Delivery System Prolonged Circulation Prolonged Circulation Time
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