PEG-modified liposomes

Since the discovery of vesicular structures, termed liposomes, by Alec Bangham, a tremendous amount of work on applications of liposomes has emerged. The use of small unilamellar liposomes as carriers of drugs for therapeutic applications has become one of the major fields in liposome research. The majority of these applications are based on the encapsulation of water-soluble molecules within the trapped volume of the liposomes. Long circulating poly(ethylene glycol) (PEG) modified liposomes with cytotoxic drugs doxorubicin, paclitaxel, vincristine, and lurtotecan are examples of clinically applied chemotherapeutic liposome formulations (1,2). 

The solid lipids and the lipophilic drugs (see Figs. 1 and 2), either as powder or stock solutions are dissolved in 5-10 mL methanol/methylene chloride (1 1, v/v) in a round bottom flask (see Note 2). PEG-modified liposomes are obtained by addition of PEG(2000)-DPPE (28 mg/mL) to the basic lipid mixtures (see Note 3). 

Therapeutic experiment with APRP(S-PEG-Modified Liposomal DPP-CNDAC... 

Other lipid compositions with synthetic lipids, hydrogenated SPC (HSPC) and PEG-modified phospholipids are often used, especially for liposome formulations intended for parenteral applications use (long circulating or stealth liposomes) (41). Several analytical methods to follow loss of lipids during the preparation steps are available. Radioactively labeled lipids ( H-DPPC, C-DPPC) or cholesterol ( H-cholesterol) or H-cholesteryl hexadecyl ether (NEN Life Science Products, Boston, MA, USA) or lipophilic fluorescence dyes (e.g. lipophilic BODIPy derivatives. Molecular Probes) are added at appropriate amounts to the initial lipid mixtures. 

Such liposomes were prepared by detergent dialysis from a mixture of phosphatidyl choline and cholesterol. Antibody modified with Wglutaryl phosphatidyl ethanolamine (NGPA) (44) was incorporated into the liposomal membrane in the process of liposome preparation. PEG modified with NGPA was also... 

Kim J K, et al. (2003). Enhancement of polyethylene glycol (PEG)-modified cationic liposome-mediated gene deliveries Effects on serum stability and transfection efficiency. J. Pharm. Pharmacol. 55 453-460. 

Research on oral liposomal delivery systems has moved forward with the development of polymer-modified liposomes. For example, targeted PEGylated liposomes furnished with folic acid for oral delivery were promising, showing enhanced permeability of dextran (used as a marker) across Caco-2 cell monolayers (Anderson et al., 1999). PEG and chitosan-coated lipid nanoparticles were constmcted as oral delivery systems for salmon calcitonin (sCT). The PEG-coated nanoparticles did not alter the transepithelial electrical resistance of Caco-2 cell monolayers, while the chitosan-coated nanoparticles showed a dose-dependent increase in the permeability of dextran across the monolayers (Garcia-Fuentes et al., 2005). It demonstrated that the favourable interaction of the chitosan-coated nanoparticles with intestinal mucosa, together with their permeation enhancing characteristics, could improve the oral absorption of sCT. 

Kuai R, Yuan W, Qin Y, Chen H, Tang J, Yuan M, Zhang Z, He Q (2010) Efficitait delivery of payload into tumor cells in a controlled manner by TAT and thiolytic cleavable PEG co-modified liposomes. Mol Pharm 7 1816-1826... 

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