Biomaterials-Enabled Antithrombotics: Recent Advances and Emerging Strategies

Overview

Journal Mol Pharm

Publisher American Chemical Society

Specialty Pharmacology

Date 2022 Sep 23

PMID 36149250

Authors

Macy M Hale

Scott H Medina

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Nanosystems in Cardiovascular Medicine: Advancements, Applications, and Future Perspectives.

Omidian H, Babanejad N, Cubeddu L Pharmaceutics. 2023; 15(7).

PMID: 37514121 PMC: 10386572. DOI: 10.3390/pharmaceutics15071935.

References

Vangijzegem T, Stanicki D, Laurent S . Magnetic iron oxide nanoparticles for drug delivery: applications and characteristics. Expert Opin Drug Deliv. 2018; 16(1):69-78. DOI: 10.1080/17425247.2019.1554647. View

Pitek A, Park J, Wang Y, Gao H, Hu H, Simon D . Delivery of thrombolytic therapy using rod-shaped plant viral nanoparticles decreases the risk of hemorrhage. Nanoscale. 2018; 10(35):16547-16555. PMC: 6145846. DOI: 10.1039/c8nr02861c. View

Ruoslahti E . Peptides as targeting elements and tissue penetration devices for nanoparticles. Adv Mater. 2012; 24(28):3747-56. PMC: 3947925. DOI: 10.1002/adma.201200454. View

Oake N, Fergusson D, Forster A, van Walraven C . Frequency of adverse events in patients with poor anticoagulation: a meta-analysis. CMAJ. 2007; 176(11):1589-94. PMC: 1867836. DOI: 10.1503/cmaj.061523. View

Weitz J, Harenberg J . New developments in anticoagulants: Past, present and future. Thromb Haemost. 2017; 117(7):1283-1288. DOI: 10.1160/TH16-10-0807. View

Wang N, Zheng W, Cheng S, Zhang W, Liu S, Jiang X . In Vitro Evaluation of Essential Mechanical Properties and Cell Behaviors of a Novel Polylactic-co-Glycolic Acid (PLGA)-Based Tubular Scaffold for Small-Diameter Vascular Tissue Engineering. Polymers (Basel). 2019; 9(8). PMC: 6418786. DOI: 10.3390/polym9080318. View

Harter K, Levine M, Henderson S . Anticoagulation drug therapy: a review. West J Emerg Med. 2015; 16(1):11-7. PMC: 4307693. DOI: 10.5811/westjem.2014.12.22933. View

Araujo C, Simon A, da Silva Honorio T, da Silva S, Valle I, da Silva L . Development of rivaroxaban microemulsion-based hydrogel for transdermal treatment and prevention of venous thromboembolism. Colloids Surf B Biointerfaces. 2021; 206:111978. DOI: 10.1016/j.colsurfb.2021.111978. View

Maitz M, Freudenberg U, Tsurkan M, Fischer M, Beyrich T, Werner C . Bio-responsive polymer hydrogels homeostatically regulate blood coagulation. Nat Commun. 2013; 4:2168. PMC: 3759053. DOI: 10.1038/ncomms3168. View

10.

Pyataev N, Petrov P, Minaeva O, Zharkov M, Kulikov O, Kokorev A . Amylase-Sensitive Polymeric Nanoparticles Based on Dextran Sulfate and Doxorubicin with Anticoagulant Activity. Polymers (Basel). 2019; 11(5). PMC: 6571953. DOI: 10.3390/polym11050921. View

11.

Lee Y, Park J, Uhm J, Kim J, Pak H, Lee M . Bleeding risk and major adverse events in patients with cancer on oral anticoagulation therapy. Int J Cardiol. 2015; 203:372-8. DOI: 10.1016/j.ijcard.2015.10.166. View

12.

Palta S, Saroa R, Palta A . Overview of the coagulation system. Indian J Anaesth. 2014; 58(5):515-23. PMC: 4260295. DOI: 10.4103/0019-5049.144643. View

13.

Houbballah R, LaMuraglia G . Clotting problems: diagnosis and management of underlying coagulopathies. Semin Vasc Surg. 2011; 23(4):221-7. DOI: 10.1053/j.semvascsurg.2010.11.001. View

14.

Dadfar S, Roemhild K, Drude N, von Stillfried S, Knuchel R, Kiessling F . Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications. Adv Drug Deliv Rev. 2019; 138:302-325. PMC: 7115878. DOI: 10.1016/j.addr.2019.01.005. View

15.

de Jong W, Borm P . Drug delivery and nanoparticles:applications and hazards. Int J Nanomedicine. 2008; 3(2):133-49. PMC: 2527668. DOI: 10.2147/ijn.s596. View

16.

Weitz J, Chan N . Advances in Antithrombotic Therapy. Arterioscler Thromb Vasc Biol. 2018; 39(1):7-12. DOI: 10.1161/ATVBAHA.118.310960. View

17.

Zhao W, Liu Q, Zhang X, Su B, Zhao C . Rationally designed magnetic nanoparticles as anticoagulants for blood purification. Colloids Surf B Biointerfaces. 2018; 164:316-323. DOI: 10.1016/j.colsurfb.2018.01.050. View

18.

Sloand J, Rokni E, Watson C, Miller M, Manning K, Simon J . Ultrasound-Responsive Nanopeptisomes Enable Synchronous Spatial Imaging and Inhibition of Clot Growth in Deep Vein Thrombosis. Adv Healthc Mater. 2021; 10(16):e2100520. DOI: 10.1002/adhm.202100520. View

19.

Park H, Otte A, Park K . Evolution of drug delivery systems: From 1950 to 2020 and beyond. J Control Release. 2021; 342:53-65. PMC: 8840987. DOI: 10.1016/j.jconrel.2021.12.030. View

20.

Hall R, Mazer C . Antiplatelet drugs: a review of their pharmacology and management in the perioperative period. Anesth Analg. 2011; 112(2):292-318. DOI: 10.1213/ANE.0b013e318203f38d. View