The Protective Effect of Poloxamer-188 on Platelet Functions

Güler, Nil; Abro, Schuharazad; Emanuele, Marty; Iqbal, Omer; Hoppensteadt, Debra; Fareed, Jawed

doi:10.1177/1076029616669785

Cited by 3 publications

(2 citation statements)

References 18 publications

(24 reference statements)

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“…P188 is safely and wildly used in the pharmaceutical industry as an excipient of formulations and an agent of drug delivery. Based on stable packaged drug, protein, or nucleotide delivery, affinity with cell membrane, and inducible cytoprotecting of P188, a recent study focuses on medicine industrial application including being sublingual permeation enhancers [ 31 ], stabilizer of anti-tumor drug [ 32 ], agent of promising blood cell viability [ 33 ], and transfection reagent of short nucleotide chains [ 34 ]. Furthermore, our study first suggests P188 not only has the potential as an adjuvant of subunit vaccines, but also as immune modulator and drug through affecting the p38MPAK pathway.…”

Section: Discussionmentioning

confidence: 99%

Poloxamer-188 Adjuvant Efficiently Maintains Adaptive Immunity of SARS-CoV-2 RBD Subunit Vaccination through Repressing p38MAPK Signaling

et al. 2022

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Poloxamer-188 (P188) is a nonionic triblock linear copolymer that can be used as a pharmaceutical excipient because of its amphiphilic nature. This study investigated whether P188 can act as an adjuvant to improve the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD) subunit vaccine. BALB/c mice were vaccinated twice with the RBD antigen alone or in combination with P188 or MF59 (a commercial adjuvant for comparison purposes). The resulting humoral and cellular immunity were assessed. Results showed that P188 helped elicit higher neutralizing activity than MF59 after vaccination. P188 induced significant humoral immune response, along with type 1 T helper (Th1) and type 2 T helper (Th2) cellular immune response when compared with MF59 due to repressing p38MAPK phosphorylation. Furthermore, P188 did not result in adverse effects such as fibrosis of liver or kidney after vaccination. In conclusion, P188 is a novel adjuvant that may be used for safe and effective immune enhancement of the SARS-CoV-2 RBD antigen.

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Section: Discussionmentioning

confidence: 99%

Poloxamer-188 Adjuvant Efficiently Maintains Adaptive Immunity of SARS-CoV-2 RBD Subunit Vaccination through Repressing p38MAPK Signaling

et al. 2022

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“…The poloxamer family of block copolymers has been in wide use for drug delivery and other biomedical applications (78). P188 has been safely used in animals and humans, including advanced clinical trials for limiting vaso-occlusive crisis in sickle cell anemia 79, 80, 81. As reviewed in detail below, synthetic membrane stabilizers are amphiphilic long-chain macromolecular block copolymers that interact with and protect the muscle sarcolemma during stress (Central Illustration, Figure 2).…”

Section: The Cardiac Membrane As a Direct Therapeutic Target In Myocamentioning

confidence: 99%

Cardiac Muscle Membrane Stabilization in Myocardial Reperfusion Injury

Houang

Bartos

Hackel

et al. 2019

JACC: Basic to Translational Science

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Highlights In myocardial ischemia, the integrity of the cardiac sarcolemma is severely stressed in the critical earliest moments upon reperfusion. Bolstering sarcolemma integrity improves myocyte survival. This review focuses on cardiac sarcolemma stability and its role as a therapeutic target in ischemia-reperfusion injury. Synthetic block copolymers have been shown to interface with the muscle membrane to confer membrane stabilization during stress. Integrated multidisciplinary research teams, spanning cardiology, physiology, chemistry, and chemical engineering are essential to guide future mechanistic and translational studies of novel chemical-based membrane stabilizers for preserving viable heart muscle during ischemia-reperfusion injury in human patients.

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Vepoloxamer Enhances Fibrinolysis of tPA (Tissue-Type Plasminogen Activator) on Acute Ischemic Stroke

Wang

Huang

et al. 2019

Stroke

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Background and Purpose— Thrombolytic treatment of acute ischemic stroke with tPA (tissue-type plasminogen activator) is hampered by its narrow therapeutic window and potential hemorrhagic complication. Vepoloxamer is a nonionic surfactant that exerts potent hemorheologic and antithrombotic properties in various thrombotic diseases. The current study investigated the effect of vepoloxamer on tPA treatment in a rat model of embolic stroke. Methods— Male Wistar rats subjected to embolic middle cerebral artery occlusion were treated with the combination of vepoloxamer and tPA, vepoloxamer alone, tPA alone, or saline initiated 4 hours after middle cerebral artery occlusion. Results— Monotherapy with tPA did not reduce infarct volume, and adversely potentiated microvascular thrombosis and vascular leakage compared with the saline treatment. Vepoloxamer monotherapy reduced infarct volume by 25% and improved brain perfusion. However, the combination treatment with vepoloxamer and tPA significantly reduced infarct volume by 32% and improved neurological function, without increasing the incidence of gross hemorrhage. Compared with vepoloxamer alone, the combination treatment with vepoloxamer and tPA robustly reduced secondary thrombosis and tPA-augmented microvascular leakage and further improved brain perfusion, which was associated with substantial reductions of serum active PAI-1 (plasminogen activator inhibitor-1) level and tPA-upregulated PAI-1 in the ischemic brain. Mechanistically, exosomes derived from platelets of ischemic rats treated with tPA-augmented cerebral endothelial barrier permeability and elevated protein levels of PAI-1 and TF (tissue factor) in the endothelial cells, whereas exosomes derived from platelets of rats subjected to the combination treatment with vepoloxamer and tPA diminished endothelial permeability augmented by tPA and fibrin and reduced PAI-1 and TF levels in the endothelial cells. Conclusions— The combination treatment with vepoloxamer and tPA exerts potent thrombolytic effects in rats subjected to acute ischemic stroke. Vepoloxamer reduces tPA-aggravated prothrombotic effect of platelet-derived exosomes on cerebral endothelial cells, which may contribute to the therapeutic effect of the combination treatment.

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The Protective Effect of Poloxamer-188 on Platelet Functions

Abstract: The protective effects of MST-188 on ADP- and collagen-induced platelet aggregation may contribute to the preservation of platelet functionality upon storage in blood banks.

Cited by 3 publications

References 18 publications

Poloxamer-188 Adjuvant Efficiently Maintains Adaptive Immunity of SARS-CoV-2 RBD Subunit Vaccination through Repressing p38MAPK Signaling

Poloxamer-188 Adjuvant Efficiently Maintains Adaptive Immunity of SARS-CoV-2 RBD Subunit Vaccination through Repressing p38MAPK Signaling

Cardiac Muscle Membrane Stabilization in Myocardial Reperfusion Injury

Vepoloxamer Enhances Fibrinolysis of tPA (Tissue-Type Plasminogen Activator) on Acute Ischemic Stroke

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