Method for preparing loaded nanoparticles

Abstract

Novel pentablock polymers having a PCL-PLA-PEG-PLA-PCL or PCL-PGA-PEG-PGA-PCL configuration, wherein PEG is polyethylene glycol, PCL is poly(ε-caprolactone), PGA is poly(glycolic acid), and PLA is poly(lactic acid), and methods of making nanoparticles from the pentablock polymers, are disclosed. The invention is also directed to a method for preparing nanoparticle compositions comprised of polymers with high levels of bioactive or diagnostic agents.

1 - 30 . (canceled) 
     
     
         31 . A method for preparing bioactive or diagnostic agent loaded nanoparticles comprising a polymer, wherein said method comprises:
 emulsifying a W 1  solution in an organic solution O to form a W 1 /O primary emulsion, wherein said W 1  solution comprises a bioactive agent or diagnostic agent in an aqueous solution, and said organic solution O comprises an organic solvent and the polymer;   emulsifying said primary emulsion in an external water phase solution W 2  to obtain a W 1 /O/W 2  double emulsion;   optionally diluting said W 1 /O/W 2  double emulsion with an aqueous solution W 3  to form an optionally diluted W 1 /O/W 2  double emulsion; and   removing said organic solvent to form said bioactive or diagnostic agent loaded nanoparticles from said optionally diluted W 1 /O/W 2  double emulsion;   wherein said bioactive or diagnostic agent has a loading of about 10 to 25%.   
     
     
         32 . The method of  claim 31  wherein said method has an initial or nominal ratio of polymer to bioactive agent or diagnostic agent of about 10:1 to 2:1. 
     
     
         33 . (canceled) 
     
     
         34 . The method of  claim 31  wherein a W 1 /O ratio represents a ratio of a volume of the W 1  solution to a volume of the organic solution O, and wherein the W 1 /O ratio is about 1:2 to 1:6. 
     
     
         35 . (canceled) 
     
     
         36 . The method of  claim 31  wherein a O/W 2  ratio represents a ratio of a volume of the organic solution O to a volume of the external water phase solution W 2 , and wherein the O/W 2  ratio is about 1:1 to 1:9. 
     
     
         37 . (canceled) 
     
     
         38 . The method of  claim 31  wherein a W 1 /O/W 2  ratio represents a ratio of a volume of the W 1  solution to a volume of the organic solution O to a volume of the external water phase solution W 2 , and wherein the W 1 /O/W 2  ratio is about 1:2:2 to 1:6:54. 
     
     
         39 . (canceled) 
     
     
         40 . The method of  claim 31  wherein a W 1 /W 2  ratio represents the ratio of a volume of the W 1  solution to a volume of the external water phase solution W 2 , and wherein the W 1 /W 2  ratio is about 1:2 to 1:54. 
     
     
         41 . (canceled) 
     
     
         42 . The method of  claim 31  wherein a W 1 /(W 2 +W 3 ) ratio represents the ratio of a volume of the W 1  solution to a volume of the external water phase solution W 2  plus a volume of the aqueous solution W 3 , and wherein the W 1 /(W 2 +W 3 ) ratio is about 1:20 to 1:100. 
     
     
         43 . The method of  claim 31  wherein a W 1 /W 3  ratio represents a ratio of a volume of the W 1  solution to a volume of the aqueous solution W 3 , and wherein the W 1 /W 3  ratio is about 1:10 to about 1:80. 
     
     
         44 . (canceled) 
     
     
         45 . The method of  claim 31  wherein a W 2 /W 3  ratio represents a ratio of a volume of the external water phase solution W 2  to a volume of the aqueous solution W 3 , and wherein the W 2 /W 3  ratio is about 1:1 to about 1:50. 
     
     
         46 . (canceled) 
     
     
         47 . The method of  claim 31  wherein said bioactive agent or diagnostic agent is hydrophilic. 
     
     
         48 . The method of  claim 31 , wherein said bioactive agent or diagnostic agent is a protein or peptide 
     
     
         49 . The method of  claim 31 , wherein said bioactive agent or diagnostic agent comprises IgG or IgG-Fab. 
     
     
         50 . The method of  claim 31 , wherein said bioactive agent or diagnostic agent comprises an enzyme. 
     
     
         51 . (canceled) 
     
     
         52 . The method of  claim 31  wherein said organic solution O comprises dichloromethane. 
     
     
         53 . The method of  claim 31  wherein said external water phase solution W 2  comprises polyvinyl alcohol in distilled deionized water. 
     
     
         54 . The method of  claim 31  wherein said aqueous solution W 3  comprises polyvinyl alcohol in distilled deionized water. 
     
     
         55 . The method of  claim 31  wherein said isolating step comprises evaporating said organic phase in said optionally diluted emulsion. 
     
     
         56 . (canceled) 
     
     
         57 . (canceled) 
     
     
         58 . The method of  claim 31 , wherein the nanoparticles have a particle size of about 300 to 700 nm. 
     
     
         59 . (canceled) 
     
     
         60 . The method of  claim 31 , wherein said bioactive or diagnostic agent loaded nanoparticles have a bioactive agent or diagnostic agent loading of about 10 to 25 wt %. 
     
     
         61 . The method of  claim 31 , wherein said bioactive or diagnostic agent loaded nanoparticles have a bioactive agent or diagnostic agent entrapment efficiency of about 45 to 90%.