Polysaccharides-based nanocomplexes for the prolonged delivery of enoxaparin: In-vitro and in-vivo evaluation

Ibrahim, Shaimaa S.; Osman, Rihab; Awad, Gehanne A.S.; Mortada, Nahed D.; Geneidi, Ahmed S.

doi:10.1016/j.ijpharm.2017.05.007

Cited by 10 publications

(5 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We further evaluated time-related changes of the reversal activity of HBC against nadroparin as an example, since HBC effect was comparable for all studied LMWHs. The almost complete neutralization of bleeding time and anti-factor Xa activity was observed for 1 h after a 5-minute infusion of HBC, whereas more than 60% of its reversal activity was maintained after 2 h. Based on the literature data (Ibrahim et al, 2017), the inhibition of factor Xa activity by LMWH expires after ~6 h from intravenous administration into rats. Thus, if a reversal of anticoagulation longer than 2 h is needed for surgical intervention or during uncontrolled bleeding, HBC should be probably administered second time or, similarly to andexanet alfa, should be kept infused till the end of surgery or bleeding.…”

Section: Discussionmentioning

confidence: 94%

Heparin-Binding Copolymer as a Complete Antidote for Low-Molecular-Weight Heparins in Rats

Kałaska

Mikłosz

Kamiński

et al. 2020

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Bleeding resulting from the application of low-molecular-weight heparins (LMWHs) may be treated with protamine sulfate but lacks efficiency; its action against anti-factor Xa activity is limited to ~60%. Moreover, protamine sulfate can cause life-threatening hypersensitivity reactions. We developed diblock heparin-binding copolymer (HBC) that can neutralize the anticoagulant activity of parenteral anticoagulants. In the present study, we explored the safety profile of HBC and its potential to reverse enoxaparin, nadroparin, dalteparin, and tinzaparin in human plasma and at in vivo conditions. HBC-LMWHs complexes were characterized using zeta potential, isothermal titration calorimetry, and dynamic light scattering. The rat cardiomyocytes and human endothelial cells were used for the assessment of in vitro toxicity. Male Wistar rats were observed for up to 4 days after HBC administration for clinical evaluation, gross necropsy, and biochemistry and histopathological analysis. Rats were treated with LMWHs alone or followed by short-time intravenous infusion of HBC, and bleeding time and anti-factor Xa activity were measured. HBC completely reversed anti-factor Xa activity prolonged in vitro by all LMWHs with an optimal weight ratio of 2.5:1. The complexes of HBC-LMWHs were below 5 µm. We observed no effects on the viability of cardiovascular cells treated with HBC at concentrations up to 0.05 mg/mL. Single doses up to 20 mg/kg of HBC were well-tolerated by rats. HBC completely reversed the effects of LMWHs on bleeding time and anti-factor Xa activity in vivo after 20 minutes, and retained ~80% and ~60% of reversal activity after 1 hour and 2 hours, respectively. Well-documented efficacy and safety of HBC both in vitro and in vivo make this polymer a promising candidate for LMWHs reversal.

show abstract

Section: Discussionmentioning

confidence: 94%

Heparin-Binding Copolymer as a Complete Antidote for Low-Molecular-Weight Heparins in Rats

Kałaska

Mikłosz

Kamiński

et al. 2020

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…In a related study, cationic chitosan was again used to form anticoagulant polyplexes, this time using Enoxaparin (Enox) as the anionic counterpart. 39 Like heparin, Enox is a highly sulfonated polysaccharide that activates antithrombin to prevent coagulation, but with the benefit of an extended circulatory half-life. Formulation optimization studies revealed that mass ratios of 1:2.5 Enox:chitosan produced 156 nm complexes, which could be further colloidally stabilized and optimized upon addition of free dextran sulfate.…”

Section: ■ Nanoscale Vehiclesmentioning

confidence: 99%

“…Nanoparticles, again, have been center stage. For example, carbohydrate nanoparticles loaded with the anticoagulant Enoxaparin (Enox) extended the drug's circulatory half-life from 5 h to over 144 h. 39 Similarly, nanoparticles prepared via disulfide cross-linking between heparin and thiol-modified polylysine extended the therapeutic effects of the anticoagulant from 8 to 36 h in mice. 58 Additional ligation of the nanoparticles to RBCs further prolonged the heparin release profile to a duration of 72 h. These results exemplify the ability of nanoparticle technologies to extend the therapeutic persistence of anticoagulants from several hours to multiple days.…”

Section: ■ Translational Applicationmentioning

confidence: 99%

“…In a related study, cationic chitosan was again used to form anticoagulant polyplexes, this time using Enoxaparin (Enox) as the anionic counterpart . Like heparin, Enox is a highly sulfonated polysaccharide that activates antithrombin to prevent coagulation, but with the benefit of an extended circulatory half-life.…”

Section: Nanoscale Vehiclesmentioning

confidence: 99%

“…Nanoparticles, again, have been center stage. For example, carbohydrate nanoparticles loaded with the anticoagulant Enoxaparin (Enox) extended the drug’s circulatory half-life from 5 h to over 144 h . Similarly, nanoparticles prepared via disulfide cross-linking between heparin and thiol-modified polylysine extended the therapeutic effects of the anticoagulant from 8 to 36 h in mice .…”

Section: Translational Applicationmentioning

confidence: 99%

See 2 more Smart Citations

Biomaterials-Enabled Antithrombotics: Recent Advances and Emerging Strategies

Hale

Medina

2022

Mol. Pharmaceutics

View full text Add to dashboard Cite

Antithrombotic and thrombolytic therapies are used to prevent, treat, and remove blood clots in various clinical settings, from emergent to prophylactic. While ubiquitous in their healthcare application, short half-lives, off-target effects, overdosing complications, and patient compliance continue to be major liabilities to the utility of these agents. Biomaterials-enabled strategies have the potential to comprehensively address these limitations by creating technologies that are more precise, durable, and safe in their antithrombotic action. In this review, we discuss the state of the art in anticoagulant and thrombolytic biomaterials, covering the nano to macro length scales. We emphasize current methods of formulation, discuss how material properties affect controlled release kinetics, and summarize modern mechanisms of clot-specific drug targeting. The preclinical efficacy of these technologies in an array of cardiovascular applications, including stroke, pulmonary embolism, myocardial infarction, and blood contacting devices, is summarized and performance contrasted. While significant advances have already been made, ongoing development efforts look to deliver bioresponsive "smart" biomaterials that will open new precision medicine opportunities in cardiology.

show abstract

Synthesis and Characterization of Naringenin-Loaded Chitosan-Dextran Sulfate Nanocarrier

Muralidharan

Shanmugam

2020

J Pharm Innov

View full text Add to dashboard Cite

Polysaccharides-based nanocomplexes for the prolonged delivery of enoxaparin: In-vitro and in-vivo evaluation

Cited by 10 publications

References 38 publications

Heparin-Binding Copolymer as a Complete Antidote for Low-Molecular-Weight Heparins in Rats

Heparin-Binding Copolymer as a Complete Antidote for Low-Molecular-Weight Heparins in Rats

Biomaterials-Enabled Antithrombotics: Recent Advances and Emerging Strategies

Synthesis and Characterization of Naringenin-Loaded Chitosan-Dextran Sulfate Nanocarrier

Contact Info

Product

Resources

About