Insertion of poly(ethylene glycol) derivatized phospholipid into pre‐formed liposomes results in prolonged in vivo circulation time

Uster, Paul S.; Allen, Theresa M.; Daniel, Barbra E.; Mendez, Cecilia J.; Newman, Mary S.; Zhu, George Z.

doi:10.1016/0014-5793(96)00452-8

Cited by 289 publications

(197 citation statements)

References 14 publications

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“…We evaluated PEG because it has been reported to decrease the interaction of macromolecules and liposomes with serum proteins and antibodies, and it is frequently used in pharmaceutical preparations to provide a hydrophilic coat and to stabilize compounds. [22][23][24][25][26] Our data indicate that PEG may play a similar role here, decreasing access of antibody to virus.…”

Section: Discussionsupporting

confidence: 52%

“…[22][23][24] When PEG is coupled to liposomes, nanoparticles and proteins, their circulating lifetime increases, the interaction with antibodies decreases, and uptake by the reticuloendothelial system decreases. 25,26 The amphipathic nature of PEG and its ability to induce cell fusion 27 suggested that it might provide an additional benefit by enhancing infection. We considered direct coupling of PEG to virus to coat and protect it.…”

Section: Introductionmentioning

confidence: 99%

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Adenovirus complexed with polyethylene glycol and cationic lipid is shielded from neutralizing antibodies in vitro

et al. 1998

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Development of neutralizing antibodies is an important hinbody binding. As a result, 50-fold higher concentrations of drance that limits repeated administration of adenoviral immune plasma were required for neutralization than with vectors for gene transfer. One way to avoid this problem adenovirus alone. However, use of the complex provided would be to coat the virus with a substance that could no appreciable protection from neutralization when vector shield it from antibodies. To develop such a system, we was delivered in vivo to immunized animals. These data coated negatively-charged adenovirus with the cationic are the first to suggest that formation of a complex around lipid GL-67 and included polyethylene glycol (PEG) in adenovirus can partially shield it from immune plasma in the complex as dioleoylphosphatidylethanolamine-PEG vitro. Despite the lack of protection in vivo, these results (DOPE-PEG). This complex enhanced gene transfer to suggest the feasibility of developing a system in which the cells that were difficult to infect both in vitro and in vivo.virus is effectively shielded from neutralizing antibodies GL-67/DOPE-PEG coated the virus and prevented antiand capable of repeat administration.

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Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Adenovirus complexed with polyethylene glycol and cationic lipid is shielded from neutralizing antibodies in vitro

et al. 1998

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“…For conjugation of DSPE-PEG2000, the postinsertion approach for liposomes was adopted, as reported elsewhere. 33 In brief, following incubation with an aqueous micellar solution of DSPE-PEG2000 for 90 minutes at 60°C, the RGD-DXRL-PEG was prepared ( Figure 1). If necessary, the liposomes were further concentrated by ultrafiltration (molecular weight cutoff 10,000, Millipore, Billerica, MA).…”

Section: Preparation Of Liposomesmentioning

confidence: 99%

Cyclic RGD peptide-modified liposomal drug delivery system: enhanced cellular uptake in vitro and improved pharmacokinetics in rats

Chen¹,

Deng²,

Zhao³

et al. 2012

IJN

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Background:Integrins α v β 3 and α v β 5 , both of which specifically recognize the Arg-Gly-Asp (RGD) motif, are overexpressed on many solid tumors and in tumor neovasculature. Thus, coupling the RGD motif to the liposomal surface for achieving active targeting can be a promising strategy for the treatment of tumors. Methods: Cyclo(Arg-Gly-Asp-D-Phe-Cys) (cRGD) was covalently coupled with the liposomal membrane surface, followed by coating with poly(ethylene glycol) (PEG) using the post-insertion technique. The coupling efficiency of cRGD was determined. Doxorubicin as a model anticancer drug was loaded into liposomes using an ammonium sulfate gradient method to investigate the encapsulation efficiency, cellular uptake by the integrin-overexpressing human glioma cell line U87MG in vitro, and pharmacokinetic properties in Sprague-Dawley rats. Results: cRGD was conjugated to the liposomal surface by a thiol-maleimide coupling reaction. The coupling efficiency reached 98%. The encapsulation efficiency of doxorubicin in liposomes was more than 98%. The flow cytometry test result showed that cRGD-modified liposomes (RGD-DXRL-PEG) had higher cell uptake by U87MG cells, compared with nontargeted liposomes (DXRL-PEG). The cellular uptake was significantly inhibited in the presence of excess free cRGD. Both the targeted (t 1/2 = 24.10 hours) and non-targeted (t 1/2 = 25.32 hours) liposomes showed long circulating properties in rat plasma. The area under the curve of the targeted and nontargeted liposomes was 6.4-fold and 8.3-fold higher than that of doxorubicin solution, respectively. Conclusion: This study indicates preferential targeting and long circulating properties for cRGD-modified liposomes in vivo, which could be used as a potential targeted liposomal drug delivery system to treat human glioma.

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“…Furthermore, as little as 0.6 mol% of PEG-DSPE depressed hepatic uptake but did not depress the bone marrow uptake. PEG-DSPE can be incorporated into the outer surface of preformed liposomes using the post incorporation method (Sou et al, 2000;Uster et al, 1996). Otherwise PEG-DSPE is mixed with other lipid components before preparation of liposomes.…”

Section: Liposomesmentioning

confidence: 99%

Advanced Drug Carriers Targeting Bone Marrow

Sou¹

2012

Recent Advances in Novel Drug Carrier Systems

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Insertion of poly(ethylene glycol) derivatized phospholipid into pre‐formed liposomes results in prolonged in vivo circulation time

Cited by 289 publications

References 14 publications

Adenovirus complexed with polyethylene glycol and cationic lipid is shielded from neutralizing antibodies in vitro

Adenovirus complexed with polyethylene glycol and cationic lipid is shielded from neutralizing antibodies in vitro

Cyclic RGD peptide-modified liposomal drug delivery system: enhanced cellular uptake in vitro and improved pharmacokinetics in rats

Advanced Drug Carriers Targeting Bone Marrow

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