Glutathione‐PEGylated liposomal methylprednisolone in comparison to free methylprednisolone: slow release characteristics and prolonged lymphocyte depression in a first‐in‐human study

Kanhai, Kawita M. S.; Zuiker, Rob; Stavrakaki, I.; Gladdines, Werner; Gaillard, Pieter J.; Klaassen, Erica S.; Groeneveld, Geert Jan

doi:10.1111/bcp.13525

Cited by 27 publications

(15 citation statements)

References 37 publications

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“…• slow release formulation with reduced toxicity and prolonged decrease in the lymphocyte count [171] PLGA Pitavastatine Healthy volunteers 40 patients, Phase I, iv administration…”

Section: Discussionmentioning

confidence: 99%

Advanced nanomedicines for the treatment of inflammatory diseases

Brusini

Varna

Couvreur

2020

Advanced Drug Delivery Reviews

149

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Inflammation, a common feature of many diseases, is an essential immune response that enables survival and maintains tissue homeostasis. However, in some conditions, the inflammatory process becomes detrimental, contributing to the pathogenesis of a disease. Targeting inflammation by using nanomedicines (i.e. nanoparticles loaded with a therapeutic active principle), either through the recognition of molecules overexpressed onto the surface of activated macrophages or endothelial cells, or through enhanced vasculature permeability, or even through biomimicry, offers a promising solution for the treatment of inflammatory diseases. After providing a brief insight on the pathophysiology of inflammation and current therapeutic strategies, the review will discuss, at a pre-clinical stage, the main innovative nanomedicine approaches that have been proposed in the past five years for the resolution of inflammatory disorders, finally focusing on those currently in clinical trials.

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“…• slow release formulation with reduced toxicity and prolonged decrease in the lymphocyte count [171] PLGA Pitavastatine Healthy volunteers 40 patients, Phase I, iv administration…”

Section: Discussionmentioning

confidence: 99%

Advanced nanomedicines for the treatment of inflammatory diseases

Brusini

Varna

Couvreur

2020

Advanced Drug Delivery Reviews

149

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“…As an example, the major results obtained with 2B3-101 in cells and animals are presented in Figure 5 . The 2B3-201 product has recently completed a phase I trial in healthy volunteers [ 146 ], while the 2B3-101 product has completed a phase I/IIa trial in patients with various forms of brain cancer ( Identifier: NCT01386580 [ 147 , 148 ]) and is currently being tested in a phase II trial in patients with breast cancer and leptomeningeal metastases (ClinicalTrials.gov Identifier: NCT01818713).…”

Section: Gsh Decoration As a Tool For Targeted Drug Delivery Systementioning

confidence: 99%

Glutathione: Antioxidant Properties Dedicated to Nanotechnologies

et al. 2018

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Which scientist has never heard of glutathione (GSH)? This well-known low-molecular-weight tripeptide is perhaps the most famous natural antioxidant. However, the interest in GSH should not be restricted to its redox properties. This multidisciplinary review aims to bring out some lesser-known aspects of GSH, for example, as an emerging tool in nanotechnologies to achieve targeted drug delivery. After recalling the biochemistry of GSH, including its metabolism pathways and redox properties, its involvement in cellular redox homeostasis and signaling is described. Analytical methods for the dosage and localization of GSH or glutathiolated proteins are also covered. Finally, the various therapeutic strategies to replenish GSH stocks are discussed, in parallel with its use as an addressing molecule in drug delivery.

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“…It is hard to evaluate to what extent the pre-medication administered to the patient played a role in avoiding IRs, but from an ethical point of view pre-treatment was mandatory to reduce the potentially life-threatening side effects of IRs. In addition, with other nano-drugs, it is known that despite pre-medication some patients still experience IRs to several types of drugs such as antibodies [60] but also anticancer therapy [34], or lately a new formulation of glutathione-PEGylated liposomal methylprednisolone [50]. Therefore, pre-medication was, and should still be administered, as a mean of prevention even though our formulation didn't give any signs of complement activation in the patient.…”

Section: Discussionmentioning

confidence: 98%

“…They measured the levels of SC5b-9 as an indication of complement activation in the plasma of patients treated with Doxil ® , and showed that the correlation between complement activation and infusion reaction was the strongest when the levels of SC5b-9 were raised 4-fold or more above the upper threshold of normal plasma levels. A recent clinical study with a formulation of glutathione-PEGylated liposomes containing methylprednisolone [50] revealed an extremely high rate of infusion related reactions (89%) in patients following drug infusion. Analysis of complement activation factors in the blood of patients revealed drastic increase in C3a factor (spiking at>1500 ng/mL) and an increase in Bb levels of more than 16-fold in all patients receiving doses of 300 mg or more of liposomal MPS.…”

Section: Discussionmentioning

confidence: 99%

PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A Correlation Between in Vitro Immunological and in Vivo Clinical Studies

Bavli¹,

Chen

Roffler

et al. 2020

Molecules

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PEGylated nanomedicines are known to induce infusion reactions (IRs) that in some cases can be life-threatening. Herein, we report a case study in which a patient with rare mediastinal and intracardiac IgG4-related sclerosing disease received 8 treatments of intravenously administered PEGylated liposomal methylprednisolone-succinate (NSSL-MPS). Due to the ethical requirements to reduce IRs, the patient received a cocktail of premedication including low dose of steroids, acetaminophen and H2 blockers before each infusion. The treatment was well-tolerated in that IRs, complement activation, anti-PEG antibodies and accelerated blood clearance of the PEGylated drug were not detected. Prior to the clinical study, an in vitro panel of assays utilizing blood of healthy donors was used to determine the potential of a PEGylated drug to activate complement system, elicit pro-inflammatory cytokines, damage erythrocytes and affect various components of the blood coagulation system. The overall findings of the in vitro panel were negative and correlated with the results observed in the clinical phase.

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Glutathione‐PEGylated liposomal methylprednisolone in comparison to free methylprednisolone: slow release characteristics and prolonged lymphocyte depression in a first‐in‐human study

Abstract: 2B3-201 is considered safe, with no clinically relevant changes in central nervous system safety parameters and no serious adverse events. In addition, 2B3-201 shows a long plasma half-life and prolonged immunosuppressive effects.

Cited by 27 publications

References 37 publications

Advanced nanomedicines for the treatment of inflammatory diseases

Advanced nanomedicines for the treatment of inflammatory diseases

Glutathione: Antioxidant Properties Dedicated to Nanotechnologies

PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A Correlation Between in Vitro Immunological and in Vivo Clinical Studies

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