Polymers & Polymerizable Lipids
Avanti Polar Lipids, Inc. is available to supply your research and pharmaceutical PEG-lipid requirements. Our PEG-lipid offerings are diverse, both in the PEG and the lipid portion of the conjugate. On the PEG side we offer mPEG's of various molecular weights and several functionalized PEG's. On the lipid side an infinite variety of lipid anchors are available or possible. Our research staff continues to develop new PEG-lipid derivatives and other biologically compatible polymeric compounds.
mPEG Phospholipid Conjugates
Avanti offers an extensive selection of mPEG phospholipid conjugates with mPEG molecular weights from 350 to 5000.
Other PEG-Lipid Derivatives
Avanti also offers several PEG-ceramide conjugates, functionalized PEG derivatives and fluorescent PEG derivatives, as well as several crosslinking lipids.
| DSPE-PEG(2000) Carboxylic Acid | | | |
Phospholipids conjugated to monomethoxy polyethyleneglycol (PEG) have been around since 1984 when Sears1 coupled, via an amide linkage, carboxy-PEG and purified soy phosphatidylethanolamine (PE). Since then the linkage between PEG and PE has been modified to include esters2 and carbamate3 derivatives, the carbamate derivative being the most widely used today. The molecular weights of the most commonly used PEG's are 2,0004,5 and 5,0006,, but PEG's ranging from 6007 to 12,0008 are also used. The lipid part of the conjugate varies from saturated9 or unsaturated PE's4 to cholesterol7 and ceramides10 with short chain (C8), intermediate chain (C14) and long chain (C20) fatty amides. The use of PEG-lipid derivatives to prolong the in vivo circulation time of liposomes and to evaluate the stearic stabilization of the amphipathic polymer has been studied by many research groups.2,11,12,13,14 The "holy grail" of liposomeology continues to be a delivery vehicle for targeting drugs to a specific biologic site. Liposome research has made great strides toward achieving this goal by the attachment of antibodies to functionalized PEG-lipid derivatives.15,16 The latest advance in the technology being the synthesis of detachable PEG-lipid conjugates.17
References
1. Sears, B.D. (1984). Synthetic Phospholipid Compounds. United States Patent 4,426,330
2. Klibanov, A.L., K. Maruyama, V.P. Torchilin, and L. Huang. (1990). Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett 268:235-7.
3. Woodle, M.C., G. Storm, M.S. Newman, J.J. Jekot, L.R. Collins, F.J. Martin, and F.C. Szoka Jr. (1992). Prolonged systemic delivery of peptide drugs by long-circulating liposomes: illustration with vasopressin in the Brattlebororat. Pharm Res 9:260-5.
4. Ng, K., L. Zhao, Y. Liu, and M. Mahapatro. (2000). The effects of polyethyleneglycol (PEG)-derived lipid on the activity of target-sensitive immunoliposome. Int J Pharm 193:157-166.
5. Ishida, T., D.L. Iden, and T.M. Allen. (1999). A combinatorial approach to producing sterically stabilized (Stealth) immunoliposomal drugs. FEBS Lett 460:129-33.
6. Liu, F. and D. Liu. (1995). Long-circulating emulsions (oil-in-water) as carriers for lipophilic drugs. Pharm Res 12:1060-4.
7. Bradley, A.J., D.V. Devine, S.M. Ansell, J. Janzen, and D.E. Brooks. (1998). Inhibition of liposome-induced complement activation by incorporated poly(ethylene glycol)-lipids. Arch Biochem Biophys 357:185-94.
8. Bedu-Addo, F.K., P. Tang, Y. Xu, and L. Huang. (1996). Interaction of polyethyleneglycol-phospholipid conjugates with cholesterol-phosphatidylcholine mixtures: sterically stabilized liposome formulations. Pharm Res 13:718-24.
9. Parr, M.J., S.M. Ansell, L.S. Choi, and P.R. Cullis. (1994). Factors influencing the retention and chemical stability of poly(ethylene glycol)-lipid conjugates incorporated into large unilamellar vesicles. Biochim Biophys Acta 1195:21-30.
10. Mok, K.W., A.M. Lam, and P.R. Cullis. (1999). Stabilized plasmid-lipid particles: factors influencing plasmid entrapment and transfection properties. Biochim Biophys Acta 1419:137-50.
11. Allen, T.M., G.A. Austin, A. Chonn, L. Lin, and K.C. Lee. (1991). Uptake of liposomes by cultured mouse bone marrow macrophages: influence of liposome composition and size. Biochim Biophys Acta 1061:56-64.
12. Mori, A., A.L. Klibanov, V.P. Torchilin, and L. Huang. (1991). Influence of the steric barrier activity of amphipathic poly(ethyleneglycol) and ganglioside GM1 on the circulation time of liposomes and on the target binding of immunoliposomes in vivo. FEBS Lett 284:263-6.
13. Woodle, M.C., L.R. Collins, E. Sponsler, N. Kossovsky, D. Papahadjopoulos, and F.J. Martin. (1992). Sterically stabilized liposomes. Reduction in electrophoretic mobility but not electrostatic surface potential. Biophys J 61:902-10.
14. Woodle, M.C. and D.D. Lasic. (1992). Sterically stabilized liposomes. Biochim Biophys Acta 1113:171-99.
15. Allen, T.M., E. Brandeis, C.B. Hansen, G.Y. Kao, and S. Zalipsky. (1995). A new strategy for attachment of antibodies to sterically stabilized liposomes resulting in efficient targeting to cancer cells. Biochim Biophys Acta 1237:99-108.
16. Bendas, G., A. Krause, U. Bakowsky, J. Vogel, and U. Rothe. (1999). Targetability of novel immunoliposomes prepared by a new antibody conjugation technique. Int J Pharm 181:79-93.
17. Zalipsky, S., M. Qazen, J.A. Walker 2nd, N. Mullah, Y.P. Quinn, and S.K. Huang. (1999). New detachable poly(ethylene glycol) conjugates: cysteine-cleavable lipopolymers regenerating natural phospholipid, diacyl phosphatidylethanolamine. Bioconjug Chem 10:703-7.
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