Immunogenicity and Rapid Blood Clearance of Liposomes Containing Polyethylene Glycol-Lipid Conjugates and Nucleic Acid

Semple, Sean C.; Harasym, Troy O.; Clow, Kathy A.; Ansell, Steven M.; Klimuk, Sandra K.; Hope, Michael J.

doi:10.1124/jpet.104.078113

Cited by 188 publications

(136 citation statements)

References 36 publications

(56 reference statements)

Supporting

Mentioning

133

Contrasting

Order By: Relevance

“…Finally, after their accumulation, they are metabolized and eliminated by the target tissues. 5,92,93 Despite all the hopes invested in conventional liposomes, they have presented various problems and pharmacological implications over the years. A major drawback of conventional liposomes is their quick capture by the RES.…”

Section: Liposomes In Nanomedicinementioning

confidence: 99%

Liposomes as nanomedical devices

Bozzuto¹,

Molinari²

2015

IJN

1,738

1,114

View full text Add to dashboard Cite

Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the “first-generation” liposomes, and liposome-based drugs on the market and in clinical trials.

show abstract

Section: Liposomes In Nanomedicinementioning

confidence: 99%

Liposomes as nanomedical devices

Bozzuto¹,

Molinari²

2015

IJN

1,738

1,114

View full text Add to dashboard Cite

show abstract

“…When PEGylated liposome-encapsulated oligonucleotide, pDNA, or RNA is repeatedly injected into the mice, a strong immune response is induced. The circulation time of the preparation decreases, and the death rate of mice significantly increases (Semple et al, 2005). Thus, an in-depth investigation on the ABC phenomenon is necessary.…”

Section: Introductionmentioning

confidence: 99%

Influence of phospholipid types and animal models on the accelerated blood clearance phenomenon of PEGylated liposomes upon repeated injection

et al. 2014

Drug Delivery

View full text Add to dashboard Cite

(2015) Influence of phospholipid types and animal models on the accelerated blood clearance phenomenon of PEGylated liposomes upon repeated injection, Drug Delivery, 22:5, 598-607, DOI: 10.3109/10717544.2014 AbstractWhen polyethylene glycol (PEG)ylated liposomes were repeatedly injected into the same animal, the second dose of liposomes would rapidly clear from the bloodstream and enhance accumulation in the liver and spleen, and this phenomenon is called ''accelerated blood clearance (ABC)''. There are many factors known to influence ABC phenomenon, in this study, we mainly focused on the effects of different phospholipids (PL) types and animal models. The effects of PL types on ABC phenomenon were examined by repeating injection of PEGylated liposomes prepared by five different types of PL (hydrogenated soy phosphatidylcholine, egg sphingomyelin, soybean phosphatidycholin, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and egg phosphatidycholin) in rats. Dramatically, repeated injection of different types of PL could induce ABC phenomenon altogether. Both t 1/2 and AUC of experimental group (EG) were lower significantly than those of control group (CG). Our results also showed that the liver accumulation of second dose increased significantly (p50.01) in all EG as compared that of CG. Interestingly, ABC phenomenon of liposomes prepared by unsaturated PL was more obvious than that of saturated PL. All the first dose could induce the antibody (anti-PEG IgM) level increasing significantly (p50.01). For different animal models, we found that after repeated injection of PEGylated liposomes, rats, mice, rabbits and guinea pigs could produce ABC phenomenon. Various PL types and animal models could all produce the ABC phenomenon. However, their extent of accelerated clearance differed. ABC phenomenon is possibly a ubiquitous immune phenomenon in life.

show abstract

“…When covering lipoplexes by polyethyleneglycol (PEG) to reduce opsonisation and MPS uptake, a decrease of transfection efficiency was observed in vitro [9] and [10]. Moreover, it was shown that the use of PEG combined with liposomal formulations containing DNA makes them less efficient in vitro [9] and more immunogenic [11].…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic acid-bearing lipoplexes: Physico-chemical characterization and in vitro targeting of the CD44 receptor

Wojcicki

Hillaireau

Nascimento

et al. 2012

Journal of Controlled Release

View full text Add to dashboard Cite

The mechanism by which hyaluronic acid (HA)-bearing lipoplexes target the A549 lung cancer cell line was evaluated. For this purpose, cationic liposomes targeting the CD44 receptor were designed thanks to the incorporation in their composition of a conjugate between high molecular weight HA and the lipid DOPE (HA-DOPE). Liposomes containing HA-DOPE were complexed at different lipids:DNA ratios with a reporter plasmid encoding the green fluorescent protein (GFP). Diameter, zeta potential, lipoplex stability and DNA protection from nucleases have been determined.Lipids:DNA ratios of 2, 4 and 6 provided a diameter around 250 nm with a zeta potential of − 30 mV.The strength of lipids:DNA interaction and the fraction of DNA protected from enzymatic degradation increased with the lipids:DNA ratio. 2D-immunoelectrophoresis demonstrated the low capacity to activate the C3 fraction of the complement system of any of these three ratios, with and without HA-DOPE. Transfection efficiency in the presence of 0, 10 and 15% of HA-DOPE or unconjugated HA, was determined on the CD44-expressing A549 cells by flow cytometry.Lipoplexes at a lipids:DNA ratio of 2 containing 10% (w/w) of HA-DOPE were the most efficient for transfection. The maximal level of GFP expression was obtained after 6 h of incubation demonstrating a slow transfection kinetics of lipoplexes. Finally, lipoplex cellular uptake, measured indirectly by the level of transfection using flow cytometry and validated by fluorescence microscopy, was shown to be mediated by the CD44 receptor and caveolae. These results demonstrate the strong specificity of DNA targeting through the CD44 receptor using HA of high molecular weight as a ligand.

show abstract

Immunogenicity and Rapid Blood Clearance of Liposomes Containing Polyethylene Glycol-Lipid Conjugates and Nucleic Acid

Cited by 188 publications

References 36 publications

Liposomes as nanomedical devices

Liposomes as nanomedical devices

Influence of phospholipid types and animal models on the accelerated blood clearance phenomenon of PEGylated liposomes upon repeated injection

Hyaluronic acid-bearing lipoplexes: Physico-chemical characterization and in vitro targeting of the CD44 receptor

Contact Info

Product

Resources

About