title: Halting hemorrhage with self-propelling particles and local drug delivery.
abstract: Approaches to locally deliver drugs to specific regions of the body are being developed for many clinical applications, including treating hemorrhage. Increasing the concentration of therapeutic coagulants in areas where clots are forming and growing can be achieved by directing them to the injury, such as with catheters or external delivery devices, or by systemically administering therapeutics that target molecular signals of vascular damage. Treating severe hemorrhage by external measures is challenging because blood flow pushes hemostatic agents outward, reducing their efficacy. This review explains that self-propelling particles may be used for delivering therapeutics, such as coagulation factors, small molecules, or other chemical or biological agents, deep into wounds during hemorrhage. A recent example of self-propelling particles is highlighted, where propulsion enhanced the efficacy of a formulation of thrombin and tranexamic acid in treating bleeding in two murine models of hemorrhage and a porcine model of fatal, non-compressible hemorrhage. Many agents exist which modulate clotting, and novel approaches that facilitate their safe delivery to sites of vascular injury could reduce the enormous number of deaths from hemorrhage that occur globally.
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: James R
authors.initials: JR
authors.lastname: Baylis
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Karen Y T
authors.initials: KY
authors.lastname: Chan
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. Electronic address: ckastrup@msl.ubc.ca.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Kastrup
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D003029:Coagulants / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D006470:Hemorrhage / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D013917:Thrombin / Q000008:administration & dosage / Q000627:therapeutic use; D014148:Tranexamic Acid / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D003029:Coagulants; D004337:Drug Carriers; D014148:Tranexamic Acid; D013917:Thrombin
keywords: biomaterials; drug delivery; incompressible Haemorrhage; micromotors; nanoparticles; trauma