Triblock copolymer stabilizers for the formation of nanoparticles encapsulating soluble biologics, therapeutics, and imaging agents

A method for forming a reformed polymer inverse nanoparticle that encapsulates a water soluble active, comprising:

• dissolving the water soluble active in an amount of a first process solvent to form a first process solution and dissolving a triblock copolymer in an amount of a second process solvent to form a second process solution;
• continuously mixing the first process solution and the second process solution with an amount of a nonprocess solvent to form a first nanoparticle solution comprising a polymer inverse nanoparticle having a core and a shell and a first nanoparticle solvent;
• using the first nanoparticle solution as an intermediate solution, adding a second nonprocess solvent to the first nanoparticle solution to form the intermediate solution, or exchanging the first nanoparticle solvent with the second nonprocess solvent to form the intermediate solution;
• and
• continuously mixing the intermediate solution with a reforming solvent to form a reformed nanoparticle solution comprising the reformed polymer inverse nanoparticle having a core and a shell,
• wherein the triblock copolymer is a linear [Block A]-[Block B]-[Block C] copolymer,
• wherein Block A is selected from the group consisting of poly(ethylene glycol) and poly(propylene oxide),
• wherein Block B is hydrophobic and is selected from the group consisting of poly(lactic acid), poly(L-lactide), poly(D-lactide), poly(D,L-lactide), poly(glycolic acid), poly(lactic-co-glycolic acid), poly(caprolactone), poly(hydroxyalkanoate), poly(3-hydroxybutyrate), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate),
• wherein Block C is hydrophilic and is selected from the group consisting of poly(aspartic acid) and poly(glutamic acid),
• wherein Block A is soluble in the second process solvent, is soluble in the nonprocess solvent, and is soluble in the reforming solvent,
• wherein Block B is soluble in the nonprocess solvent and is insoluble in the reforming solvent,
• wherein Block C is soluble in the first process solvent, is soluble in the second process solvent, and is insoluble in the nonprocess solvent,
• wherein the water soluble active and Block C are in the core of the polymer inverse nanoparticle and are in the core of the reformed polymer inverse nanoparticle,
• wherein Block C is not in the shell of the reformed polymer inverse nanoparticle,
• wherein Block C does not extend away from the core into the reforming solvent,
• wherein the first process solvent is more polar than the nonprocess solvent,
• wherein the second process solvent is more polar than the nonprocess solvent,
• wherein an intermediate solvent is the intermediate solution without the polymer inverse nanoparticle,
• wherein the reforming solvent is more polar than the intermediate solvent,
• wherein the amount of the first process solvent, the amount of the second process solvent, and the amount of the nonprocess solvent, when mixed in the absence of the water soluble active or the triblock copolymer, yields a mixture of a single phase or a mixture of which a polar phase is less than 20% of a second phase that is less polar than the polar phase,
• wherein the first process solvent is selected from the group consisting of dimethylsulfoxide (DMSO), propanol, ethanol, methanol, water, and a combination,
• wherein the second process solvent is selected from the group consisting of dimethylsulfoxide (DMSO), propanol, ethanol, methanol, water, and a combination,
• wherein the nonprocess solvent is selected from the group consisting of dichloromethane, chloroform, acetone, tetrahydrofuran (THF), and a combination,
• wherein the second nonprocess solvent is selected from dichloromethane, chloroform, acetone, tetrahydrofuran (THF), and a combination,
• wherein the reforming solvent is selected from water, methanol, ethanol, propanol, and a combination.