Irradiated biodegradable polymer microparticles

Abstract

In one aspect, the present invention provides sterile microparticle compositions comprising biodegradable microparticles, which comprise at least one biodegradable polymer. In other aspects, the present invention provides methods of making and using such compositions as well as articles of manufacture and kits containing the same.

1 . An article of manufacture comprising a sealed container and a sterile dry microparticle composition contained within said sealed container, said microparticle composition comprising blank biodegradable microparticles that comprise a biodegradable polymer, wherein said sealed container is configured to allow for the introduction and removal of sterile fluid. 
     
     
         2 . The article of manufacture of  claim 1 , wherein said sealed container comprises a septum. 
     
     
         3 . The article of manufacture of  claim 1 , wherein said article of manufacture is gamma irradiated. 
     
     
         4 . The article of manufacture of  claim 1 , wherein said biodegradable microparticles comprise poly(lactide-co-glycolide). 
     
     
         5 . The article of manufacture of  claim 1 , wherein upon the addition of water in an amount such that the microparticle composition has a concentration of 25 mg/ml, a suspension is formed in which the microparticles have a D(v,0.5) value that is between 0.5 and 5 μm. 
     
     
         6 . The article of manufacture of  claim 1 , wherein said microparticle composition is a lyophilized microparticle composition. 
     
     
         7 . The article of manufacture of  claim 6 , wherein said microparticle composition further comprises a cryoprotective agent. 
     
     
         8 . The article of manufacture of  claim 1 , wherein said container is a single dose container comprising between 4 and 50 mg of said microparticles, and 5 and 150 mg of one or more pharmaceutical excipients. 
     
     
         9 . The article of manufacture of  claim 1 , wherein said microparticle composition comprises charged microparticles. 
     
     
         10 . The article of manufacture of  claim 9 , wherein said charged microparticles comprise a charged species in addition to said biodegradable polymer. 
     
     
         11 . The article of manufacture of  claim 10 , wherein said charged species is selected from an anionic detergent and a cationic detergent. 
     
     
         12 . The article of manufacture of  claim 1 , wherein upon the addition of water in an amount such that the microparticle composition is in a concentration of 25 mg/mL, a suspension is formed in which the microparticles have a zeta potential that is greater than +20 mV or less than −20 mV at physiological pH. 
     
     
         13 . The article of manufacture of  claim 1 , wherein said microparticle composition further comprises an immunological adjuvant. 
     
     
         14 . The article of manufacture of  claim 13 , wherein said immunological adjuvant is selected from monophosphoryl lipid A analogues, small molecule immune potentiators, muramyl tripeptide phosphatidylethanolamine and tocopherols. 
     
     
         15 . The article of manufacture of  claim 1 , further comprising a label indicating one or more members of the group consisting of (a) a statement that the microparticle formulation has been gamma-irradiated, (b) storage information, (c) dosing information, and (d) instructions regarding how to administer the microparticle formation. 
     
     
         16 . The article of manufacture of  claim 15 , wherein said label indicates that the microparticle composition can be combined with a fluid composition comprising water and one or more antigens. 
     
     
         17 . The article of manufacture of  claim 15 , further comprising packaging material, wherein the sealed container and label are contained within said packaging material. 
     
     
         18 . The article of manufacture of  claim 13 , wherein said immunological adjuvant is an activator of a Toll-like receptor (TLR). 
     
     
         19 . The article of manufacture of  claim 13 , wherein said immunological adjuvant is an activator of a Toll-like receptor (TLR) selected from Toll-like receptor 2 (TLR 2), Toll-like receptor 7 (TLR 7), Toll-like receptor 8 (TLR8), or a combination thereof. 
     
     
         20 . A kit comprising the article of manufacture of  claim 1  and an additional sealed container that is configured to allow for the introduction and removal of sterile fluid, said additional sealed container containing a sterile antigenic composition that comprises an antigen. 
     
     
         21 . The kit of  claim 20 , wherein said antigenic composition is a lyophilized composition. 
     
     
         22 . The kit of any of  claim 20 , wherein said antigenic composition comprises an antigen selected from a peptide-containing antigen and a polynucleotide-containing antigen. 
     
     
         23 . The kit of any of  claim 20 , further comprising a sterile aqueous liquid, a syringe, or both. 
     
     
         24 . A process comprising:
 combining (a) a sterile dry microparticle composition that comprises blank biodegradable microparticles with (b) an aqueous fluid that comprises an antigen; and   administering the combination to a vertebrate subject within 30 minutes of mixing.   
     
     
         25 . The process of  claim 24 , wherein said sterile dry microparticle composition is gamma irradiated.