Microparticles, methods for their preparation and use

Abstract

The invention relates to microparticles comprising a crosslinked gel and methods for making and using same.

1 . Microparticles comprising:
 a crosslinked gel;   wherein the microparticles have a coefficient of variation in the size distribution of the microparticles of from about 0.03 to about 0.05 and wherein the microparticles have at least one dimension measuring from about 5 μm to about 200 μm.   
     
     
         2 . The microparticles of  claim 1 , wherein the crosslinked gel comprises one or more crosslinked linear polysaccharides. 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . The microparticles of  claim 2 , wherein the crosslinked linear polysaccharide comprises a crosslinking agent. 
     
     
         6 . The microparticles of  claim 5 , wherein the crosslinking agent comprises divalent cations. 
     
     
         7 . (canceled) 
     
     
         8 . The microparticles of  claim 1 , wherein the microparticles are substantially spherical or are rod-, crescent- or hook-shaped. 
     
     
         9 . (canceled) 
     
     
         10 . The microparticles of  claim 8 , wherein the microparticles are core-shell microparticles. 
     
     
         11 . (canceled) 
     
     
         12 . The microparticles of  claim 10 , wherein the core is a liquid core, a solid core or a gas core. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . The microparticles of  claim 10 , wherein at least one of the core and the shell comprises one or more cells. 
     
     
         16 . The microparticles of  claim 1 , wherein the microparticles comprise an active agent, magnetic nanoparticles, or pores. 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . Microparticles comprising:
 a Ca 2+ -crosslinked alginate gel;   wherein the microparticles have a coefficient of variation in the size distribution of the microparticles of from about 0.03 to about 0.05 and wherein the microparticles have at least one dimension measuring from about 5 μm to about 200 μm.   
     
     
         22 . A method of forming the microparticles of  claim 1 , the method comprising:
 forming microdroplets comprising one or more crosslinkable linear polysaccharides and one or more crosslinking agents;   contacting the microdroplets with a crosslinking promoter to promote crosslinking of the one or more crosslinkable linear polysaccharides.   
     
     
         23 . The method of  claim 22 , wherein the crosslinking agent does not substantially crosslink the one or more crosslinkable linear polysaccharides in an initial state, but, upon contacting with the crosslinking promoter, crosslinks the one or more crosslinkable linear polysaccharides in a second state. 
     
     
         24 . The method of  claim 23 , wherein the first state comprises a sequestered state of the one or more crosslinking agents and the second state comprises an unsequestered state of the one or more crosslinking agents. 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 22 , wherein said forming comprises microfluidically forming the microdroplets. 
     
     
         27 . The method of  claim 22 , wherein crosslinking agent comprises divalent cations. 
     
     
         28 . (canceled) 
     
     
         29 . The method of  claim 27 , wherein the divalent cations are sequestered. 
     
     
         30 . The method of  claim 29 , wherein the sequestered divalent cations are chelated. 
     
     
         31 . The method of  claim 30 , wherein the chelated divalent cations comprise Ca 2+ -EDTA. 
     
     
         32 . The method of  claim 22 , wherein said crosslinking promoter comprises a change in the pH, a change in the temperature, a change in the ionic strength or combinations thereof. 
     
     
         33 . The method of  claim 32 , wherein said crosslinking promoter comprises a change in the pH. 
     
     
         34 . The method of  claim 33 , wherein the change in the pH is effected with an acid. 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . The method of  claim 27 , wherein the divalent cations are sequestered and the crosslinking promoter causes sequestered divalent cations to be sufficiently freed from sequestration such that crosslinking of the one or more crosslinkable linear polysaccharides is promoted. 
     
     
         39 . A method of forming the microparticles of  claim 21 , the method comprising:
 forming microdroplets comprising alginate and Ca 2+ -EDTA; and   contacting the microdroplets with a crosslinking promoter to promote crosslinking of the alginate.   
     
     
         40 . A method for delivering one or more microparticles of  claim 1  to a location in a subject in need thereof or to an area in need thereof the method comprising (i) providing or obtaining one or more microparticle comprising an active agent; and (ii) delivering the microparticle to a location in a subject in need thereof or a location in an area in need thereof. 
     
     
         41 . A system comprising one or more microparticles of  claim 1  and one or more cells encapsulated in the one or more microparticles. 
     
     
         42 . (canceled)