Artificial platelets for treating catastrophic bleeding
View Patent ↗Artificial dense granules composed of a sterically stabilized liposome shell encapsulating a polyphosphate nanoparticle core are provided as are methods for their production and use in the treatment of a severe hemorrhagic event.
1. A composition comprising a sterically stabilized liposome shell encapsulating an inorganic polyphosphate nanoparticle core, wherein:
(a) the sterically stabilized liposome shell comprises polyethylene glycol covalently conjugated to a glycerophospholipid; and
(b) the inorganic polyphosphate nanoparticle core is prepared by:
precipitating inorganic polyphosphate under aqueous conditions at physiological pH and salt conditions to form nanoparticles, wherein the inorganic polyphosphate has
the structure wherein n is at least 100 and the physiological salt is calcium chloride, thereby producing an inorganic polyphosphate nanoparticle core consisting of calcium, phosphate and oxygen.
2. The composition of claim 1 , wherein the sterically stabilized liposome shell further comprises a phospholipid, a sterol, an amine-functionalized lipid or polymer, amphiphilic peptide, polyelectrolyte, amphiphilic copolymer or a derivative or combination thereof.
3. The composition of claim 1 , wherein the sterically stabilized liposome shell comprises phosphatidylcholine and 1,2-di-palmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000].
4. The composition of claim 1 , wherein the sterically stabilized liposome shell comprises cholesterol.
5. A kit comprising the composition of claim 1 .
6. The composition of claim 1 , wherein the inorganic polyphosphate nanoparticle core is a precipitated particle of polyphosphate that is between 100 nm and 250 nm in diameter.