Polymers & Polymerizable Lipids

Poly(ethylene glycol)-Lipid Conjugates

Polyethylene glycol (PEG)-lipid conjugates have been used extensively to improve circulation times for liposome encapsulated drugs, including doxorubicin1,2, mitoxantrone3, and the lipophilic prodrug of 5-fluorodeoxyuridine.4 Recently, new applications have been developed using PEGylated liposomes. PEG modified liposomes encapsulating hemoglobin provides a long circulating red cell substitute.5 Delivery of proteins, including a sustained injectable delivery system for insulin6, streptokinase7, and superoxide dismutase8 have recently been described. In addition to injectable applications, oral delivery of peptides has been demonstrated using insulin.9 Cationic liposomes incorporating PEG lipid have been used as carriers for oligonucleotides resulting in enhanced uptake by cells.10 The work described above utilizing PEG lipids was performed using PEG conjugated to phosphatidyl-ethanolamine. A neutral PEG lipid derivative has been characterized in which the PEG moiety is linked to ceramide. By varying the acyl chain length of the ceramide, the retention time in the liposome could be modulated which directly affected the circulation time of the liposome and the plasma concentration of the drug.11 However, short acyl chain PEG ceramides proved to be superior for transfection because the PEG ceramide would dissociate from the stabilized plasmid-lipid particle surface, transforming the complex from a stable particle to a transfection competent entity.12,13,14 Also, some improvement in transfection was noted when short PEG polymers (PEG 750) were incorporated into the PEG ceramide rather than PEG 2000 or PEG 5000 polymers.13 Avanti now offers an extensive group of PEG-lipid conjugates incorporating both a range of acyl chain compositions and PEG polymer species, as well as offering PEG derivatives based on the ceramide and phosphatidylethanolamine lipid anchors. PEG-lipid conjugates incorporating functionalized PEG termini (e.g., MPB, PDP, and Biotin) have been prepared. Please contact a Product Specialist to discuss your specific requirements. 1,2-Diacyl-sn-Glycero-3-Phosphoethanolamine-N -[Methoxy(Polyethylene glycol)- 350] (mPEG 350 PE)

Purity >99%

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350] (ammonium salt)

1,2-Diacyl-sn-Glycero-3-Phosphoethanolamine-N -[Methoxy(Polyethylene glycol)- 550] (mPEG 550 PE)

Purity >99%

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550] (ammonium salt)

1,2-Diacyl-sn-Glycero-3-Phosphoethanolamine-N -[Methoxy(Polyethylene glycol)- 750] (mPEG 750 PE)

Purity >99%

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750] (ammonium salt)

1,2-Diacyl-sn-Glycero-3-Phosphoethanolamine-N -[Methoxy(Polyethylene glycol)-1000] (mPEG 1000 PE)

Purity >99%

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000] (ammonium salt)

1,2-Diacyl-sn-Glycero-3-Phosphoethanolamine-N -[Methoxy(Polyethylene glycol)-2000] (mPEG 2000 PE)

Purity >99%

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (ammonium salt)

1,2-Diacyl-sn-Glycero-3-Phosphoethanolamine-N -[Methoxy(Polyethylene glycol)-3000] (mPEG 3000 PE)

Purity >99%

1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine-N-[Methoxy(Polyethylene glycol)-3000] (Ammonium Salt)

1,2-Diacyl-sn-Glycero-3-Phosphoethanolamine-N -[Methoxy(Polyethylene glycol)-5000] (mPEG 5000 PE)

Purity >99%

1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine-N-[Methoxy(Polyethylene glycol)-5000] (Ammonium Salt)

N-Acyl-Sphingosine-1-[Succinyl (Methoxy Polyethylene Glycol) 750] (mPEG 750 Ceramide)

Purity >99%

N-Palmitoyl-Sphingosine-1-[Succinyl(Methoxy(Polyethylene Glycol)750] (C16 mPEG 750 Ceramide)

N-Acyl-Sphingosine-1-[Succinyl(Methoxy Polyethylene Glycol) 2000] (mPEG 2000 Ceramide)

Purity >99%

N-Palmitoyl-Sphingosine-1-[Succinyl(MethoxyPolyethylene Glycol)2000] (C16 mPEG 2000 Ceramide)

N-Acyl-Sphingosine-1-[Succinyl(Methoxy Polyethylene Glycol) 5000] (mPEG 5000 Ceramide)

Purity >99%

N-Palmitoyl-Sphingosine-1-[Succinyl(Methoxy(Polyethylene Glycol)5000] (C16 mPEG 5000 Ceramide)

References

1. Working, P.K., Newman, M.S., Sullivan, T., Yarrington, J. (1999) Reduction of the cardiotoxicity of doxorubicin in rabbits and dogs by encapsulation in longcirculating, pegylated liposomes., J Pharmacol Exp Ther, 289:11281133.
   
2. Gabizon, A., Goren, D., Cohen, R., Barenholz, Y. (1998) Development of liposomal anthracyclines: from basics to clinical applications, J Controlled Release 53:275279.
   
3. AdlakhaHutcheon, G., Bally, M.B., Shew, C.R., Madden, T.D. (1999) Controlled destabilization of a liposomal drug delivery system enhances mitoxantrone antitumor activity, Nat Biotechnol 17:775779.
   
4. Koning, G.A., Morselt, H.W., Velinova, M.J., Donga, J., Gorter, A., Allen, T.M., Zalipsky, S., Kamps, J.A., Scherphof, G.L. (1999) Selective transfer of a lipophilic prodrug of 5fluorodeoxyuridine from immunoliposomes to colon cancer cells, Biochim Biophys Acta 1420:153167.
   
5. Phillips, W.T., Klipper, R.W., Awasthi, V.D., Rudolph, A.S., Cliff, R., Kwasiborski, V., Goins, B.A. (1999) Polyethylene glycolmodified liposomeencapsulated hemoglobin: a long circulating red cell substitute, J Pharmacol Exp Ther 288:665670.
   
6. Kim, A., Yun, M.O., Oh, Y.K., Ahn, W.S., Kim, C.K. (1999) Pharmacodynamics of insulin in polyethylene glycolcoated liposomes, Int J Pharm 180:7581.
   
7. Kim, I.S., Choi, H.G., Choi, H.S., Kim, B.K., Kim, C.K. (1998) Prolonged systemic delivery of streptokinase using liposome, Arch Pharm Res 21:248252.
   
8. Corvo, M.L., Boerman, O.C., Oyen, W.J., Van Bloois, L., Cruz, M.E., Crommelin, D.J., Storm, G. (1999) Intravenous administration of superoxide dismutase entrapped in long circulating liposomes. II. In vivo fate in a rat model of adjuvant arthritis, Biochim Biophys Acta 1419:325334.
   
9. Iwanaga, K., Ono, S., Narioka, K., Kakemi, M., Morimoto, K., Yamashita, S., Namba, Y., Oku, N. (1999) Application of surfacecoated liposomes for oral delivery of peptide: effects of coating the liposome's surface on the GI transit of insulin, J Pharm Sci 88:248252.
   
10. Meyer, O., Kirpotin, D., Hong, K., Sternberg, B., Park, J.W., Woodle, M.C., Papahadjopoulos, D. (1998) Cationic liposomes coated with polyethylene glycol as carriers for oligonucleotides, J Biol Chem 273:1562115627.
    
11. Webb, M.S., Saxon, D., Wong, F.M., Lim, H.J., Wang, Z., Bally, M.B., Choi, L.S., Cullis, P.R., Mayer, L.D. (1998) Comparison of different hydrophobic anchors conjugated to poly(ethylene glycol): effects on the pharmacokinetics of liposomal vincristine, Biochim Biophys Acta 1372:272282.
    
12. Wheeler, J.J., Palmer, L., Ossanlou, M., MacLachlan, I., Graham, R.W., Zhang, Y.P., Hope, M.J., Scherrer, P., Cullis, P.R. (1999) Stabilized plasmidlipid particles: construction and characterization, Gene Ther 6:271281.
    
13. Mok, K.W., Lam, A.M., Cullis, P.R. (1999) Stabilized plasmid-lipid particles: factors influencing plasmid entrapment and transfection properties, Biochim Biophys Acta 1419:137150.
    
14. Zhang, Y., Sekirov, L., Saravolac, E., Wheeler, J., Tardi, P., Clow, K., Leng, E., Sun, R., Cullis, P., Scherrer, P. (1999) Stabilized plasmid-lipid particles for regional gene therapy: formulation and transfection properties, Gene Ther 6:14381447.