Nanoformulations of pazopanib, compositions comprising the same and methods of treating osteoarthritis
Disclosed herein are nanoparticles comprising Pazopanib or a derivative thereof encapsulated by the copolymer poly (lactic-co-glycolic acid) (PLGA). Also disclosed herein are methods for treating osteoarthritis, inhibiting or preventing cartilage degeneration, and reducing or inhibiting pain-associated depression in subjects with joint pain with nanoparticles comprising Pazopanib or a derivative thereof.
1 . A nanoparticle comprising or consisting of Pazopanib encapsulated by poly (lactic-co-glycolic acid) (PLGA), poly (ethylene glycol)-b-poly (e-caprolactone) (PEG-b-PCL), or a combination thereof, wherein the nanoparticle is in a pegylated liposome.
2 . The nanoparticle of claim 1 , wherein the nanoparticle has a diameter of from 500 nm to 600 nm.
3 . The nanoparticle of claim 1 , wherein the nanoparticle comprises about 2 to about 25 weight percent of the Pazopanib.
4 . The nanoparticle of claim 1 , wherein the ratio of PLGA to Pazopanib is approximately 1:1.
5 . The nanoparticle of claim 1 , further comprising a cryo-protective agent.
6 . The nanoparticle of claim 1 , wherein the nanoparticle further contains a positively charged molecule or a positively charged lipid.
7 . A pharmaceutical composition comprising one or more of the nanoparticles of claim 1 .
8 . The pharmaceutical composition of claim 7 , wherein the encapsulation efficiency of Pazopanib is between 80% and about 90%.
9 . The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition is formulated as a liquid, a lyophilized powder, a cream, or an ointment.
10 . The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition is substantially free of dimethylsulfoxide (DMSO), methanol, and/or chloroform.
11 . A method of inhibiting cartilage degeneration in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising the nanoparticle of claim 1 .
12 . A method of reducing pain or reducing joint pain in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising the nanoparticle of claim 1 .
13 . A method of treating osteoarthritis in a subject in need thereof, the method comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising the nanoparticle of claim 1 .
14 . A method of treating a joint condition in a subject in need thereof, the method comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising the nanoparticle of claim 1 .
15 . The method of claim 14 , wherein the joint condition is a joint injury.
16 . The method of claim 15 , wherein the joint injury is a traumatic injury or a post-operative injury.
17 . The method of claim 15 , wherein the joint injury is a repetitive strain injury.
18 . A method of enhancing tissue regeneration in a subject in need thereof, the method comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising the nanoparticle of claim 1 and mesenchymal stem cells.
19 . The method of claim 18 , wherein the administration is via intraarticular administration.