期刊
JOURNAL OF LIPOSOME RESEARCH
卷 16, 期 3, 页码 175-183出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/08982100600848769
关键词
liposome; targeting; cancer chemotherapy; doxorubicin; mitomycin C; peglation; folate receptor; mouse tumor model
Coating of liposomes with polyethylene-glycol (PEG) by incorporation in the liposome bilayer of PEG-derivatized lipids results in inhibition of liposome uptake by the reticulo-endothelial system and significant prolongation of liposome residence time in the blood stream. Parallel developments in drug loading technology have improved the efficiency and stability of drug entrapment in liposomes, particularly with regard to cationic amphiphiles such as anthracyclines. An example of this new generation of liposomes is a formulation of pegylated liposomal doxorubicin known as Doxil (R) or Caelyx (R), whose clinical pharmacokinetic profile is characterized by slow plasma clearance and small volume of distribution. A hallmark of these long-circulating liposomal drug carriers is their enhanced accumulation in tumors. The mechanism underlying this passive targeting effect is the phenomenon known as enhanced permeability and retention (EPR) which has been described in a broad variety of experimental tumor types. Further to the passive targeting effect, the liposome drug delivery platform offers the possibility of grafting tumor-specific ligands on the liposome membrane for active targeting to tumor cells, and potentially intracellular drug delivery. The pros and cons of the liposome platform in cancer targeting are discussed vis-a-vis nontargeted drugs, using as an example a liposome drug delivery system targeted to the folate receptor.
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