Nanoparticles and methods of use
This disclosure relates to nanoparticles, compositions, methods of making, and methods of use thereof.
1. A composition comprising:
a nanoparticle comprising a core and an outer layer comprising a polymer surrounding the core; and
a biomolecule selectively encapsulated in the outer layer of the nanoparticle;
wherein the polymer exhibits temperature-dependent conformational changes that change the size of the nanoparticle by an amount sufficient to provide for encapsulation of the biomolecule from an aqueous medium substantially free of organic solvent, wherein the composition is prepared by a method comprising:
(a) preparing a composition comprising the nanoparticle comprising the core and the outer layer comprising the polymer surrounding the core; an aqueous medium substantially free of organic solvent; and the biomolecule dissolved or suspended in the aqueous medium;
(b) subjecting the composition to a first temperature at which the polymer expands to allow entry of the biomolecule into the outer layer; and
(c) subjecting the composition to a second temperature at which the polymer contracts to encapsulate the biomolecule in the outer layer; and
wherein the polymer surrounding the core is not crosslinked.
2. The composition of claim 1 , wherein the amount sufficient to provide for encapsulation of the biomolecule from an aqueous medium substantially free of organic solvent is in the range of about 5% to about 500%.
3. The composition of claim 1 , wherein the core comprises an aliphatic polyester polymer selected from the group consisting of: a polylactic acid, a polyglycolic acid, and a copolymer of lactic acid and glycolic acid.
4. The composition of claim 1 , wherein the outer layer comprises a poloxamer having the formula:
wherein a is an integer in the range of about 2 to about 200 and b is an integer in the range of about 10 to about 100.
5. The composition of claim 4 , wherein the poloxamer polymer comprises a poly(propylene oxide) central chain in a range from about 3000 g/mol to about 5000 g/mol.
6. The composition of claim 4 , wherein the poloxamer polymer comprises a poly(ethylene oxide) content in a range from about 60% to about 80% by weight.
7. The composition of claim 1 , wherein the biomolecule is erythropoietin, insulin, human growth hormone, interleukin-2 or interleukin-10.
8. The composition of claim 1 , wherein:
the core comprises an aliphatic polyester polymer selected from the group consisting of: a polylactic acid, a polyglycolic acid, and a copolymer of lactic acid and glycolic acid; and
the outer layer comprises a poloxamer having the formula:
wherein a is an integer in the range of about 2 to about 200 and b is an integer in the range of about 10 to about 100.
9. The composition of claim 1 , wherein the first temperature is in the range of about 0° C. to about 20° C., and the second temperature is in the range of about 20° C. to about 50° C.
10. A method of delivering a therapeutic biomolecule to a subject in need thereof, the method comprising administering to the subject in need thereof a therapeutically effective amount of a composition of claim 1 .
11. The method of claim 10 , wherein the therapeutic biomolecule is selected from the group consisting of: erythropoietin, insulin, human growth hormone, interleukin-2 and interleukin-10.