DRUG LOADED POLYMERIC NANOPARTICLES AND METHODS OF MAKING AND USING SAME
The present disclosure generally relates to nanoparticles having about 0.2 to about 35 weight percent of a therapeutic agent; and about 10 to about 99 weight percent of biocompatible polymer such as a diblock poly(lactic) acid-poly(ethylene)glycol. Other aspects of the invention include methods of making such nanoparticles.
1 . A therapeutic nanoparticle comprising:
about 0.2 to about 35 weight percent of a therapeutic agent;
about 10 to about 99 weight percent of a diblock poly(lactic) acid-poly(ethylene)glycol copolymer or a diblock poly(lactic)-co-poly (glycolic) acid-poly(ethylene)glycol copolymer; and
about 0 to about 75 weight percent poly(lactic) acid or poly(lactic) acid-co-poly (glycolic) acid.
2 . The therapeutic nanoparticle of claim 1 wherein said therapeutic agent is a taxane.
3 . (canceled)
4 . The therapeutic nanoparticle of claim 1 , wherein the hydrodynamic diameter of therapeutic nanoparticle is about 60 to about 120 nm.
5 . (canceled)
6 . The therapeutic nanoparticle of claim 1 , wherein the therapeutic nanoparticles substantially retains the therapeutic agent for at least 5 days at 25° C.
7 . The therapeutic nanoparticle of claim 1 , comprising about 10 to about 20 weight percent of a taxane agent.
8 . The therapeutic nanoparticle of claim 1 , comprising about 40 to about 90 weight percent poly(lactic) acid-poly(ethylene)glycol copolymer.
9 . The therapeutic nanoparticle of claim 8 , wherein said poly(lactic) acid-poly(ethylene)glycol copolymer comprises poly(lactic acid) having a number average molecular weight of about 15 to 100 kDa and poly(ethylene)glycol having a number average molecular weight of about 2 to about 10 Da.
10 . (canceled)
11 . The therapeutic nanoparticle of claim 1 , wherein the particle substantially immediately releases less than about 5% of the therapeutic agent over 1 hour when placed in a phosphate buffer solution at room temperature.
12 . (canceled)
13 . The therapeutic nanoparticle of claim 1 , wherein the particle substantially immediately releases less than about 10% of the therapeutic agent when placed in a phosphate buffer solution at either 37° C. or room temperature.
14 . The therapeutic nanoparticle of claim 1 comprising about 30 to about 50 weight percent PLA-PEG, about 30 to about 50 weight percent PLA or PLGA, and about 15 to about 25 weight percent active agent.
15 - 18 . (canceled)
19 . The therapeutic nanoparticle of claim 1 , further comprising about 0.2 to about 30 weight percent PLA-PEG functionalized with a targeting ligand.
20 . The therapeutic nanoparticle of claim 1 , further comprising about 0.2 to about 30 weight percent poly (lactic) acid-co poly (glycolic) acid-PEG-functionalized with a targeting ligand.
21 . The therapeutic nanoparticle of claim 19 or 20 , wherein the targeting ligand is covalently bound to the PEG.
22 . The therapeutic nanoparticle of claim 1 , further comprising about 0.2 to about 10 weight percent PLA-PEG functionalized with a targeting ligand.
23 . The therapeutic nanoparticle of claim 1 , further comprising about 0.2 to about 10 mole percent PLA-PEG-GL2 or poly (lactic) acid-co poly (glycolic) acid-PEG-GL2.
24 . The therapeutic nanoparticle of claim 1 , further comprising a polymeric compound selected from:
wherein R 1 is selected from the group consisting of H, and a C 1 -C 20 alkyl group optionally substituted with halogen;
R 2 is a bond, an ester linkage, or amide linkage;
R 3 is an C 1 -C 10 alkylene or a bond;
x is 50 to about 1500;
y is 0 to about 50; and
z is about 30 to about 200.
25 - 34 . (canceled)
35 . A composition comprising a plurality of nanoparticles of claim 1 , and a pharmaceutically acceptable excipient.
36 . (canceled)
37 . A pharmaceutical composition comprising:
a plurality of polymeric nanoparticles each comprising about 0.2 to about 35 weight percent of a therapeutic agent, about 70 to about 99 weight percent of a biocompatible polymer, and optionally a fatty alcohol; wherein the biocompatible polymer is selected from the group consisting of: a) poly(lactic) acid-poly(ethylene)glycol copolymer; b) poly(lactic)-co-poly (glycolic) acid-poly(ethylene)glycol copolymer; c) a combination of a) or b) and poly (lactic) acid or polylactic-co-glycolic acid copolymer; and
a pharmaceutically acceptable excipient.
38 . The pharmaceutical composition of claim 37 , wherein the pharmaceutically acceptable excipient is sucrose.
39 - 47 . (canceled)