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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 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 phosphatidylethanolamine. 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
While PEG-lipid conjugates have long been used to prolong circulation times of liposome encapsulated drugs, targeting these delivery
vehicles to specific biologic sites was not so readily achieved. Liposome research has made great strides towards achieving this goal
by 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 polymer
species, as well as offering PEG derivatives based on the ceramide and phosphatidylethanolamine lipid anchors. PEG-lipid conjugates
incorporating functionalized PEG termini are available for the attachment of targeting agents; these include Maleimide, PDP, Biotin, Amine
and Carboxylic acid.
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 liposomes 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 plasmidlipid 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 plasmidlipid particles for regional gene therapy:
formulation and transfection properties. Gene Ther 6:14381447.
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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continued overleaf
Revised 020415
Avanti
Number
Lipid
Anchor
Avanti
Number
Lipid
Anchor
Avanti
Number
Lipid
Anchor
Avanti
Number
mPEG 350
DMPE
880410
DPPE
880400
DSPE
880420
DOPE
880430
mPEG 550
DMPE
880510
DPPE
880500
DSPE
880520
DOPE
880530
mPEG 750
DMPE
880610
DPPE
880600
DSPE
880620
DOPE
880630
mPEG 1000
DMPE
880710
DPPE
880700
DSPE
880720
DOPE
880730
mPEG 2000
DMPE
880150
DPPE
880160
DSPE
880120
DOPE
880130
mPEG 3000
DMPE
880310
DPPE
880300
DSPE
880320
DOPE
880330
mPEG 5000
DMPE
880210
DPPE
880200
DSPE
880220
DOPE
880230
Avanti Number
Lipid Anchor
Avanti Number
mPEG 750
C8 Ceramide
880670
C16 Ceramide
880680
mPEG 2000
C8 Ceramide
880170
C16 Ceramide
880180
mPEG 5000
C8 Ceramide
880270
C16 Ceramide
880280
Functionalized PEG-Lipids
Number
DSPE-PEG (2000)-DBCO
880229
880228
880121
880125
880126
880127
Crosslinking Lipids
Number
880122
23:2 Diyne PC
870016
880128
880129
23:2 Diyne PE
790145
880124
16:0-23:2 Diyne PC
790146
880123
16:0-23:2 Diyne PE
790147