Avanti Brochure PEG Lipids

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LONG CIRCULATING LIPOSOMES AND MEMBRANE TAGGING

Poly(Ethylene Glycol)-Lipid Conjugates

18:1 PEG350 PE Avanti Number 880430

Polyethylene glycol (PEG)-lipid conjugates have been used extensively to improve circulation times for liposome encapsulated drugs,including doxorubicin 1,2 , mitoxantrone 3, and the lipophilic prodrug of 5-fluorodeoxyuridine. 4 Recently, new applications have been developedusing PEGylated liposomes. PEG modified liposomes encapsulating hemoglobin provides a long circulating red cell substitute. 5 Deliveryof proteins, including a sustained injectable delivery system for insulin 6, streptokinase 7, and superoxide dismutase 8 have recently beendescribed. In addition to injectable applications, oral delivery of peptides has been demonstrated using insulin. 9 Cationic liposomesincorporating 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 phosphatidylethanolamine. A neutral PEGlipid derivative has been characterized in which the PEG moiety is linked to ceramide. By varying the acyl chain length of the ceramide, theretention time in the liposome could be modulated which directly affected the circulation time of the liposome and the plasma concentrationof the drug. 11 However, short acyl chain PEG ceramides proved to be superior for transfection because the PEG ceramide would dissociatefrom 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 ratherthan PEG 2000 or PEG 5000 polymers. 13 While PEG-lipid conjugates have long been used to prolong circulation times of liposome encapsulated drugs, targeting these deliveryvehicles to specific biologic sites was not so readily achieved. Liposome research has made great strides towards achieving this goalby the attachment of antibodies to functionalized PEG-lipid conjugates. 15,16 The latest advance in the technology being the synthesis of

detachable PEG-lipid conjugates. 17 Avanti now offers an extensive group of PEG-lipid conjugates incorporating both a range of acyl chain compositions and PEG polymerspecies, as well as offering PEG derivatives based on the ceramide and phosphatidylethanolamine lipid anchors. PEG-lipid conjugatesincorporating functionalized PEG termini are available for the attachment of targeting agents; these include Maleimide, PDP, Biotin, Amineand Carboxylic acid.References1. Working, P.K., Newman, M.S., Sullivan, T., Yarrington, J. (1999) Reduction of the cardiotoxic ity of doxorubicin in rabbits and dogs by encapsulation in

long-circulating, pegylated liposomes. J Pharmacol Exp Ther, 289:1128-1133.2. Gabizon, A., Goren, D., Cohen, R., Barenholz, Y. (1998) Development of liposomal anthracyclines: from basics to clinical applications. J Controlled Release 53:275-279.3. Adlakha-Hutcheon, G., Bally, M.B., Shew, C.R., Madden, T.D. (1999) Controlled destabiliza tion of a liposomal drug delivery system enhances mitoxantrone antitumor activity.

Nat Biotechnol 17:775-779.4. 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

5-fluorodeoxyuridine from immunoliposomes to colon cancer cells. Biochim Biophys Acta 1420:153-167.5. Phillips, W.T., Klipper, R.W., Awasthi, V.D., Rudolph, A.S., Cliff, R., Kwasiborski, V., Goins, B.A. (1999) Polyethylene glycol-modified liposome-encapsulated

hemoglobin: a long circulating red cell substitute. J Pharmacol Exp Ther 288:665-670.6. Kim, A., Yun, M.O., Oh, Y.K., Ahn, W.S., Kim, C.K. (1999) Pharmacodynamics of insulin in polyethylene glycol-coated liposomes. Int J Pharm 180:75-81.7. 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 21:248-252.8. 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 1419:325-334.9. Iwanaga, K., Ono, S., Narioka, K., Kakemi, M., Morimoto, K., Yamashita, S., Namba, Y., Oku, N. (1999) Application of surface-coated liposomes for oral delivery of peptide:

effects of coating the liposome’s surface on the GI transit of insulin. J Pharm Sci 88:248-252.10. 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

oligonucleot ides. J Biol Chem 273:15621-15627.11. Webb, M.S., Saxon, D., Wong, F.M., Lim, H.J., Wang, Z., Bally, M.B., Choi, L.S., Culli s, 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 1372:272-282.12. 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 plasmid-lipid particl es: construction

and characterization. Gene Ther 6:271-281.13. Mok, K.W., Lam, A.M., Cullis, P.R. (1999) Stabilized plasmid-lipid particles: factors influencing plasmid entrapment and transfection properties. Biochim Biophys Acta

1419:137-150.14. Zhang, Y., Sekirov, L., Saravolac, E., Wheeler, J., Tardi, P., Clow, K., Leng, E., Sun, R., Cull is, P., Scherrer, P. (1999) Stabilized plasmid-lipid particles for regiona l gene therapy:

formulation and transfection properties. Gene Ther 6:1438-1447.15. 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). Targetabili ty 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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Polymers & Polymerizable LipidsMethoxy(Polyethylene glycol) Derivatives of Phosphatidylethanolamine

Lipid Anchor

AvantiNumber

Lipid Anchor

AvantiNumber

Lipid Anchor

AvantiNumber

Lipid Anchor

AvantiNumber

mPEG 350 DMPE 880410 DPPE 880400 DSPE 880420 DOPE 880430







Methoxy(Polyethylene glycol) Derivatives of Ceramide*

Lipid Anchor Avanti Number Lipid Anchor Avanti Number

mPEG 750 C8 Ceramide 880670 C16 Ceramide 880680



Functionalized PEG-Lipids Number

DSPE-PEG (2000)-DBCO 880229

DSPE-PEG (2000) Azide 880228

DSPE-PEG (2000) Succinyl 880121

DSPE-PEG (2000) Carboxylic Acid 880125

DSPE-PEG (2000) Maleimide 880126

DSPE-PEG (2000) PDP 880127

DSPE-PEG (2000) Cyanur 880122

DSPE-PEG (2000) Amine 880128DSPE-PEG (2000) Biotin 880129

DSPE-PEG (2000) Folate 880124

DSPE-PEG (5000) Folate 880123

*PEG-Ceramide contains ester linkagesbetween the PEG and ceramide moieties whichallow the compound to be easily metabolized.More stable linkages can be manufacturedupon request. Please contact a ProductSpecialist to discuss your specific requirements.

For more details: www.avantilipids.com Phone: 800-227-0651 Email: [email protected]

Crosslinking Lipids Number

23:2 Diyne PC 870016

23:2 Diyne PE 790145

16:0-23:2 Diyne PC 790146

16:0-23:2 Diyne PE 790147

Avanti Brochure PEG Lipids

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