Nanoparticles for delivery of active agents
Milled nanoparticles comprising a biologically active agent, at least one biopolymer and a coating containing at least one coating which is a polymer or ligand are produced using milling and coating techniques which have not previously been used for these applications.
1. A pharmaceutical composition, comprising:
planetary ball milled nanoparticles comprising:
a biologically active agent;
polyethylene glycol; and
at least one biopolymer selected from the group consisting of starch, cellulose, collagen, lactose and alginate,
wherein the nanoparticles are coated with a coating agent comprising at least one of polycaprolactone and polyethylene glycol and wherein the planetary ball milled nanoparticles are prepared by a method comprising the steps of:
(a) mixing the at least one biopolymer dissolved in an aqueous solution with the biologically active agent to form a first mixture;
(b) mixing the first mixture with polyethylene glycol to form a second mixture;
(c) drying the second mixture;
(d) producing nanoparticles of the dried second mixture by planetary ball milling; and
(e) coating the planetary ball milled nanoparticles with the coating agent.
2. The composition of claim 1 , wherein said nanoparticles have a size range of 5-30 nm.
3. The composition of claim 1 , wherein said nanoparticles have a size range of 30-180 nm.
4. The composition of claim 1 , wherein the biologically active agent is an anti-cancer agent.
5. The composition of claim 4 , wherein the anti-cancer agent is paclitaxel, or cisplatin.
6. The composition of claim 1 , wherein the coating agent comprises polycaprolactone.
7. The composition of claim 6 , wherein the coating agent further comprises a peptide conjugated to polycaprolactone.
8. The composition of claim 7 , wherein the peptide binds specifically to a target cell.
9. The composition of claim 6 , wherein the coating agent further comprises a folic acid conjugated to polycaprolactone.
10. The composition of claim 1 , wherein the nanoparticles are coated with a single or double coating of polycaprolactone.
11. The composition of claim 1 , wherein the nanoparticles are coated with a triple coating of polycaprolactone.
12. A pharmaceutical composition comprising:
planetary ball milled nanoparticles comprising:
an anti-cancer agent;
polyethylene glycol; and
at least one biopolymer selected from the group consisting of starch, cellulose, collagen, lactose and alginate,
wherein the nanoparticles have a size in the range of 5-30 nm, and wherein the particles are coated with a coating agent comprising polycaprolactone and wherein the planetary ball milled nanoparticles are prepared by a method comprising the steps of:
(a) mixing the at least one biopolymer dissolved in an aqueous solution with the anti-cancer agent to form a first mixture;
(b) mixing the first mixture with polyethylene glycol to form a second mixture;
(c) drying the second mixture;
(d) producing nanoparticles of the dried second mixture by planetary ball milling; and
(e) coating the planetary ball milled nanoparticles with the coating agent.
13. The pharmaceutical composition of claim 12 , wherein the coating agent comprises polycaprolactone conjugated to a cancer-targeting peptide.
14. The pharmaceutical composition of claim 12 , wherein the coating agent comprises polycaprolactone conjugated to a cancer-targeting antibody.
15. The pharmaceutical composition of claim 12 , wherein the coating agent comprises polycaprolactone conjugated to folic acid.
16. A pharmaceutical composition, comprising:
planetary ball milled particles comprising:
an anti-cancer agent selected from the group of paclitaxel and cisplatin;
polyethylene glycol; and
a biopolymer selected from the group consisting of starch, cellulose, collagen, lactose and alginate,
wherein the particles have a size in the range of 5 nm to 50 μm, and wherein the particles are coated with one or more layers of polycaprolactone and wherein the planetary ball milled particles are prepared by a method comprising the steps of:
(a) mixing the biopolymer dissolved in an aqueous solution with the anti-cancer agent to form a first mixture;
(b) mixing the first mixture with polyethylene glycol to form a second mixture;
(c) drying the second mixture;
(d) producing particles of the dried second mixture by planetary ball milling; and
(e) coating the planetary ball milled particles with polycaprolactone.
17. The pharmaceutical composition of claim 16 , wherein the particles are coated with one or two layers of polycaprolactone.
18. The pharmaceutical composition of claim 16 , wherein the particles are coated with three layers of polycaprolactone.
19. The pharmaceutical composition of claim 16 , wherein the polycaprolactone is conjugated to a cancer-targeting peptide.
20. The pharmaceutical composition of claim 16 , wherein the polycaprolactone is conjugated to folic acid.