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Liposomal Nanomedicines: An Emerging Field
1 Department of Chemistry, University College of the Fraser Valley, Abbotsford, British Columbia, Canada Correspondence: Address correspondence to: Pieter R. Cullis, FRSC, Department of Biochemistry and Molecular Biology, Life Sciences Centre, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC, Canada V6T 1Z3; e-mail: pieterc{at}interchange.ubc.ca. Liposomal nanoparticles (LNs) encapsulating therapeutic agents, or liposomal nanomedicines (LNMs), represent one of the most advanced classes of drug delivery systems, with several currently on the market and many more in clinical trials. During the past 20 years, a variety of techniques have been developed for encapsulating both conventional drugs and the new genetic drugs (plasmid DNA–containing therapeutic genes, anti-sense oligonucleotides, and small, interfering RNA [siRNA]) within LNs encompassing a very specific set of properties: a diameter centered on 100 nm, a high drug-to-lipid ratio, excellent retention of the encapsulated drug, and a long (> 6 hours) circulation lifetime. Particles with these properties tend to accumulate at sites of disease, such as tumors, where the endothelial layer is "leaky" and allows extravasation of particles with small diameters. Thus, LNs protect the drug during circulation, prevent it from reaching healthy tissues, and permit its accumulation at sites of disease. We will discuss recent advances in this field involving conventional anticancer drugs as well as gene-delivery, immunostimulatory, and gene-silencing applications involving the new genetic drugs. LNMs have the potential to offer new treatments in such areas as cancer therapy, vaccine development, and cholesterol management.
Key Words: Liposomal nanoparticles • drug delivery • enhanced permeation and retention • gene therapy • antisense oligonucleotides • siRNA Abbreviations: APC, antigen presenting cells • CHOP, chemotherapy treatment composed of cyclophosphamide, doxorubicin, vincristine, and prednisone • CpG, unmethylated CpG dinucleotides • DODAC, N, N-dioleyl-N, N-dimethylammonium chloride • DODAP, 1, 2-dioleoyl-3-(dimethylamino)propane • DODMA, 1, 2-dioleyloxy-N, N-dimethyl-3-aminopropane • DOPE, dioleoylphos-phatidylethanolamine • dsRNA, double-strand RNA • LN, liposomal nanoparticle • LNM, liposomal nanomedicine • MLVs, multilamellar vesicles • NK, natural killer • ODNs, oligodeoxynucleotides • PEG, poly(ethylene glycol) • PEGCerC14, PEG-ceramide containing 14 carbon fatty acid • PEGCerC20, PEG-ceramide containing 20 carbon fatty acid • PEG-S-DSG, PEG covalently bonded to distearoylglycerol • RISC, RNA-induced silencing complex • RNAi, RNA interference • SALP, stabilized antisense lipid particles • siRNA, small, interfering RNA • SNALP, stabilized nucleic acid lipid particles • SPLP, stabilized plasmid lipid particles • ssRNA, single-strand RNA • SVP, spontaneous vesicle formation • TLR, toll-like receptors
Toxicologic Pathology, Vol. 36, No. 1,
21-29 (2008) |
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