Inhibition of Liposome-Induced Complement Activation by Incorporated Poly(Ethylene Glycol)-Lipids

Bradley, Amanda J.; Devine, Dana V.; Ansell, Steven M.; Janzen, Johan; Brooks, Donald E.

doi:10.1006/abbi.1998.0798

Cited by 121 publications

(64 citation statements)

References 47 publications

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“…An increase in the size of liposomes from SUVs (39-43 nm) to LUVs (317-394 nm) resulted in an increase in liposome uptake by the RES from 35.9 to 73.7% (Uchiyama et al, 1995). The rapid clearance of LUVs may be due to the high extent of complement activation by larger particles (Bradley et al, 1998;. In addition, it is believed that the half-life of unilamellar vesicles also follows a biphasic model similar to MLVs as observed with Doxil and the liposomal formulation of docetaxel (DTX; Fig.…”

Section: A Pharmacokinetics and Pharmacodynamics Of Lipid-based Nanomentioning

confidence: 99%

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

2016

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Section: A Pharmacokinetics and Pharmacodynamics Of Lipid-based Nanomentioning

confidence: 99%

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

2016

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“…This can be achieved by, for example, adding PEGlipids to the liposome formulation. 46,47 The information on how the architecture and hydrophilicity of the lipid headgroups influence the interactions with DNA is of fundamental interest and there is a need for rationalization based on systematic studies. However, such biophysical studies demand substantial amounts of the lipid molecules.…”

Section: Introductionmentioning

confidence: 99%

Effect of Headgroup on DNA−Cationic Surfactant Interactions

Dasgupta¹,

Das²,

Dias³

et al. 2007

J. Phys. Chem. B

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The interaction behavior of DNA with different types of hydroxylated cationic surfactants has been studied. Attention was directed to how the introduction of hydroxyl substituents at the headgroup of the cationic surfactants affects the compaction of DNA. The DNA-cationic surfactant interaction was investigated at different charge ratios by several methods like UV melting, ethidium bromide exclusion, and gel electrophoresis. Studies show that there is a discrete transition in the DNA chain from extended coils (free chain) to a compact form and that this transition does not depend substantially on the architecture of the headgroup. However, the accessibility of DNA to ethidium bromide is preserved to a significantly larger extent for the more hydrophilic surfactants. This was discussed in terms of surfactant packing. Observations are interpreted to reflect that the surfactants with more substituents have a larger headgroup and therefore form smaller micellar aggregates; these higher curvature aggregates lead to a less efficient, "patch-like" coverage of DNA. The more hydrophilic surfactants also presented a significantly lower cytotoxicity, which is important for biotechnological applications.

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“…It has been previously shown that PEG-lipid can reduce the nonspecific binding of various proteins, including BSA, laminin, and fibronectin to glass surface (Du et al, 1997). Incorporation of PEG-lipids into liposomes can also prevent complement binding to liposome surface (Bradley et al, 1998). As well, endocytosis of liposomes in vitro by macrophages was shown to be reduced by incorporating PEG-lipids (Zeisig et al, 1996;Miller et al, 1998;Johnstone et al, 2001).…”

mentioning

confidence: 98%

“…As well, endocytosis of liposomes in vitro by macrophages was shown to be reduced by incorporating PEG-lipids (Zeisig et al, 1996;Miller et al, 1998;Johnstone et al, 2001). In general, the protective effect of PEG-lipids depends on its polymer size as well as grafting density (Kenworthy et al, 1995;Zeisig et al, 1996;Du et al, 1997;Bradley et al, 1998;Miller et al, 1998;Needham et al, 1999). However, our laboratory has recently demonstrated that this protective effect could actually be due to selective binding of proteins that is mediated, in part, by the presence of surface-grafted PEG (Johnstone et al, 2001).…”

mentioning

confidence: 99%

Prevention of Antibody-Mediated Elimination of Ligand-Targeted Liposomes by Using Poly(Ethylene glycol)-Modified Lipids

Li¹,

Mayer²,

Bally³

2002

J Pharmacol Exp Ther

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One of the major obstacles in the development of ligandtargeted liposomes is poor liposome circulation longevity as a result of antibody-mediated elimination of these highly immunogenic carriers. Because studies from our laboratory suggest that it is not possible to reduce the immunogenicity of ligandconjugated liposomes by using surface-grafted poly(ethylene glycol) (PEG), we investigated the usefulness of PEG in protecting hapten-conjugated liposomes from elimination by an existing immune response that was previously established against the hapten. Using biotin as a model hapten, a strong biotinspecific antibody response was generated in mice by using bovine serum albumin-biotin. When these animals were challenged with liposomes containing biotin-conjugated lipid (1 or 0.1%), these liposomes were rapidly eliminated. Incorporation of PEG-lipids into these liposomes substantially reduced biotinspecific antibody binding as measured using an in vitro antibody consumption assay. However, depending on the hapten concentration, significant reductions in antibody binding through the use of PEG-lipids may not be sufficient to protect these liposomes from rapid elimination in vivo. Complete protection of liposomes was only achieved when the biotin concentration on liposome surface was low (0.1%) and with 5 mol% of either 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy(polyethylene glycol)-2000] or 1,2-dipalmatoyl-sn-glycero-3-phosphoethanolamine-n-methoxy(polyethylene glycol)-2000]. The use of 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy(polyethylene glycol)-2000] (up to 15 mol%) was not effective in protecting liposomes from rapid elimination in vivo, indicating the limited usefulness of this highly exchangeable PEG-lipid. In conclusion, our in vivo and in vitro data indicate that liposomes can be protected from antibody-mediated elimination by using the right type and concentration of PEG-lipids. This result has important implication in the development of ligand-targeted liposomes.Active targeting can be achieved by conjugating macromolecules such as antibodies, peptides, and ligands of natural receptors onto liposome surfaces to improve the specificity of these drug carriers to disease sites (Vingerhoeds et al., 1994). Although active targeting of liposomes has met with some success both in vitro and in vivo (Park et al., 1995;Kirpotin et al., 1997;Gabizon et al., 1999), further development of ligand-targeted liposomes for in vivo use remains a challenge due to the immunogenicity of the drug carriers bearing surface ligands that function as antigenic haptens (Phillips and Emili, 1991;Phillips et al., 1994;Phillips and Dahman, 1995). Repeated administration of these liposomes becomes problematic because the pharmacokinetic and biodistribution behaviors of the carrier change after subsequent injections of the drug carrier (Shek and Heath, 1983;Phillips and Emili, 1991;Phillips et al., 1994;Harding et al., 1997;Tardi et al., 1997;Dams et al., 2000). Enhanced elimination of the liposomes...

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Inhibition of Liposome-Induced Complement Activation by Incorporated Poly(Ethylene Glycol)-Lipids

Cited by 121 publications

References 47 publications

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

Effect of Headgroup on DNA−Cationic Surfactant Interactions

Prevention of Antibody-Mediated Elimination of Ligand-Targeted Liposomes by Using Poly(Ethylene glycol)-Modified Lipids

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