Overcoming anti-PEG antibody mediated accelerated blood clearance of PEGylated liposomes by pre-infusion with high molecular weight free PEG

McSweeney, Morgan D.; Price, Lauren; Wessler, Timothy; Ciociola, Elizabeth C.; Herity, Leah B.; Piscitelli, Joseph; DeWalle, Alexander C.; Harris, Taylor N.; Chan, Andy K.P.; Saw, Ran Sing; Hu, Pan; Jennette, J. Charles; Forest, M. Gregory; Cao, Yanguang; Montgomery, Stephanie A.; Zamboni, William C.; Lai, Samuel K.

doi:10.1016/j.jconrel.2019.08.017

Cited by 58 publications

(34 citation statements)

References 47 publications

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“…Moreover, the prepared formulations exhibited enhanced antitumor effects by killing both drug-sensitive and drug-resistant glioma cells. However, the repeated administration of the quercetin-TMZ liposomal formulations to rats led to a slightly accelerated blood clearance, a phenomenon that perturbed the pharmacokinetic profile of liposomes, which were rapidly eliminated from circulation [48,49]. Still, such a phenomenon is not always observed, which renders the development of TMZ-based liposomal formulations challenging.…”

Section: Stealth Liposomesmentioning

confidence: 99%

Liposomal-Based Formulations: A Path from Basic Research to Temozolomide Delivery Inside Glioblastoma Tissue

et al. 2022

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Glioblastoma (GBM) is a lethal brain cancer with a very difficult therapeutic approach and ultimately frustrating results. Currently, therapeutic success is mainly limited by the high degree of genetic and phenotypic heterogeneity, the blood brain barrier (BBB), as well as increased drug resistance. Temozolomide (TMZ), a monofunctional alkylating agent, is the first line chemotherapeutic drug for GBM treatment. Yet, the therapeutic efficacy of TMZ suffers from its inability to cross the BBB and very short half-life (~2 h), which requires high doses of this drug for a proper therapeutic effect. Encapsulation in a (nano)carrier is a promising strategy to effectively improve the therapeutic effect of TMZ against GBM. Although research on liposomes as carriers for therapeutic agents is still at an early stage, their integration in GBM treatment has a great potential to advance understanding and treating this disease. In this review, we provide a critical discussion on the preparation methods and physico-chemical properties of liposomes, with a particular emphasis on TMZ-liposomal formulations targeting GBM developed within the last decade. Furthermore, an overview on liposome-based formulations applied to translational oncology and clinical trials formulations in GBM treatment is provided. We emphasize that despite many years of intense research, more careful investigations are still needed to solve the main issues related to the manufacture of reproducible liposomal TMZ formulations for guaranteed translation to the market.

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Section: Stealth Liposomesmentioning

confidence: 99%

Liposomal-Based Formulations: A Path from Basic Research to Temozolomide Delivery Inside Glioblastoma Tissue

et al. 2022

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“…29 However, as PEG is an exogenous compound, administration of PEGylated formulations can induce an immunoglobulin M (IgM) response by the spleen, which results in accelerated blood clearance (referred to as the "ABC phenomenon") upon repeated dosing of PEGylated nanomedicine. 96,97 Other nonexogenous stealth strategies have also been explored including the use of proline-alanine-serine (PAS) (PASylation) 98,99 and CD47, a marker of "self" over-expressed on red blood cell membranes to prolong blood circulation. 100 Further research is warranted to progress these compounds into nanoformulations approved for clinical use.…”

Section: The Bio-nano Interface: Improving Nanoparticle Fate and Nano...mentioning

confidence: 99%

“…Conjugation with the hydrophilic and neutrally charged polyethylene glycol (PEG), referred to as PEGylation, is well known to significantly increase blood circulation time, and multiple PEGylated nanoformulations are commercially and clinically available . However, as PEG is an exogenous compound, administration of PEGylated formulations can induce an immunoglobulin M (IgM) response by the spleen, which results in accelerated blood clearance (referred to as the “ABC phenomenon”) upon repeated dosing of PEGylated nanomedicine. , Other nonexogenous stealth strategies have also been explored including the use of proline–alanine–serine (PAS) (PASylation) , and CD47, a marker of “self” overexpressed on red blood cell membranes to prolong blood circulation . Further research is warranted to progress these to nanoformulations for clinical use.…”

Section: The Bio–nano Interface: Improving Nanoparticle Fate and Nano...mentioning

confidence: 99%

In Vivo T Cell-Targeting Nanoparticle Drug Delivery Systems: Considerations for Rational Design

et al. 2021

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T cells play an important role in immunity and repair and are implicated in diseases, including blood cancers, viral infections, and inflammation, making them attractive targets for the treatment and prevention of diseases. Over recent years, the advent of nanomedicine has shown an increase in studies that use nanoparticles as carriers to deliver therapeutic cargo to T cells for ex vivo and in vivo applications. Nanoparticle-based delivery has several advantages, including the ability to load and protect a variety of drugs, control drug release, improve drug pharmacokinetics and biodistribution, and site-or cell-specific targeting. However, the delivery of nanoparticles to T cells remains a major technological challenge, which is primarily due to the nonphagocytic nature of T cells. In this review, we discuss the physiological barriers to effective T cell targeting and describe the different approaches used to deliver cargo-loaded nanoparticles to T cells for the treatment of disease such as T cell lymphoma and human immunodeficiency virus (HIV). In particular, engineering strategies aiming to improve nanoparticle internalization by T cells, including ligand-based targeting, will be highlighted. These nanoparticle engineering approaches are expected to inspire the development of effective nanomaterials that can target or manipulate the function of T cells for the treatment of T cell-related diseases.

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“…Various strategies have been developed to attenuate or abolish the ABC phenomenon [11,21,22), including the pre-injection of high-molecular-weight PEG [23] or anti-PEG scFv, the regulation of the physical and chemical properties of PEGylated nanomedicines [14,24], adjusting the administration regimens [25,26], and replacing it with other polymers or co-modi cations [27][28][29]. For materials such as mPEG 2000 -DSPE, the junction (amide bond) between the hydrophilic PEG chain and hydrophobic DSPE fragment may be the key site for the recognition and mediation of the scavenging of PEGylated nanomedicines by anti-PEG IgM [30].…”

Section: Introductionmentioning

confidence: 99%

PEGylated nanoemulsions containing 1,2-distearoyl-sn-glycero-3-phosphoglycerol induced weakened accelerated blood clearance phenomenon

Gao

Yan

et al. 2022

Drug Deliv. and Transl. Res.

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Injections of polyethylene glycol (PEG)-modi ed nanomedicines can lead to an accelerated clearance of the next dose of PEGylated nanomedicines, which is referred to as the accelerated blood clearance (ABC) phenomenon. It has been reported that anti-PEG IgM plays an important role in the induction of the ABC phenomenon, identifying the interface between the main chain of PEG and the hydrophobic segment of the repeated injections of the PEGylated nanocarriers, resulting in increased liver uptake and loss of long cycle characteristics. In this study, we demonstrated that the 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG) in PEGylated nanoemulsions (PEs) may mask this interface between the main chain of PEG and the hydrophobic segment, inhibiting the recognition and binding of anti-PEG IgM to PEs, and evidently weakening the ABC phenomenon of PEs. This will provide a novel strategy to improve the curative effect of PEGylated nanocarriers.

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Overcoming anti-PEG antibody mediated accelerated blood clearance of PEGylated liposomes by pre-infusion with high molecular weight free PEG

Cited by 58 publications

References 47 publications

Liposomal-Based Formulations: A Path from Basic Research to Temozolomide Delivery Inside Glioblastoma Tissue

Liposomal-Based Formulations: A Path from Basic Research to Temozolomide Delivery Inside Glioblastoma Tissue

In Vivo T Cell-Targeting Nanoparticle Drug Delivery Systems: Considerations for Rational Design

PEGylated nanoemulsions containing 1,2-distearoyl-sn-glycero-3-phosphoglycerol induced weakened accelerated blood clearance phenomenon

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