Long Circulating Nanoparticles for Sustained Release of Therapeutic Agents

Abstract

The present disclosure is directed in part to a biocompatible nanoparticle composition comprising a plurality of non-colloidal long circulating nanoparticles, each comprising a α-hydroxy polyester-co-polyether and a therapeutic agent, wherein such disclosed compositions provide a therapeutic effect for at least 12 hours.

1 . A nanoparticle comprising a polymer matrix and a therapeutic agent coupled to the polymer matrix wherein the polymer matrix is biodegradable and/or biocompatible. 
     
     
         2 . The nanoparticle of  claim 1 , wherein the therapeutic agent is an anti-cancer agent. 
     
     
         3 . The nanoparticle of  claim 2 , wherein the therapeutic agent is docetaxel. 
     
     
         4 . The nanoparticle of  claim 1 , wherein the therapeutic agent is a peptide. 
     
     
         5 . The nanoparticle of  claim 1 , wherein the polymer matrix comprises an α-hydroxy polyester. 
     
     
         6 . The nanoparticle of  claim 5 , wherein the polymer matrix is selected from the group consisting of polylactide, poly(lactide-co-glycolide), PEGylated polymer of lactide, PEGylated copolymer of lactide and glycolide, or combinations thereof. 
     
     
         7 . The nanoparticle of  claim 2 , wherein the docetaxel is coupled to a PEGylated polymer of lactide. 
     
     
         8 . The nanoparticle of  claim 1 , further comprising a surfactant. 
     
     
         9 . The nanoparticle of  claim 1 , comprising more than one therapeutic agent. 
     
     
         10 . The nanoparticle of  claim 9 , wherein the more than one therapeutic agent each may be selected from the group consisting of an agent useful in the treatment of cancer. 
     
     
         11 . The nanoparticle of  claim 10 , wherein the polymer matrix is coupled to a therapeutic agent selected from the group consisting of: doxorubicin, gemcitabine, daunorubicin, procarbazine, mitomycin, cytarabine, etoposide, methotrexate, 5-fluorouracil, vinblastine, vincristine, bleomycin, paclitaxel, docetaxel, mitoxantrone, mitoxantrone hydrochloride, aldesleukin, asparaginase, busulfan, carboplatin, cladribine, camptothecin, dacarbazine, eniluracil, deoxycytidine, 5-azacytosine, 5-azadeoxycytosine, allopurinol, 2-chloroadenosine, trimetrexate, aminopterin, oxaplatin, picoplatin, tetraplatin, satraplatin, platinum-DACH, ormaplatin, epirubicin, etoposide phosphate, 9-aminocamptothecin, 10,11-methylenedioxycamptothecin, karenitecin, 9-nitrocamptothecin, vindesine, L-phenylalanine mustard, ifosphamidemefosphamide, perfosfamide, trophosphamide carmustine, semustine, epothilones A-E, tomudex, 6-mercaptopurine, 6-thioguanine, amsacrine, etoposide phosphate, karenitecin, acyclovir, valacyclovir, ganciclovir, amantadine, rimantadine, lamivudine, zidovudine, bevacizumab, trastuzumab, and rituximab. 
     
     
         12 . The nanoparticle of  claim 10 , wherein the polymer matrix is coupled to a therapeutic agent selected from the group consisting of docetaxel, oxaplatin, picoplatin, tetraplatin, satraplatin, carboplatin, or camptothecin. 
     
     
         13 . The nanoparticle of  claim 12 , wherein the nanoparticle includes a therapeutic agent encapsulated within, surrounded by, or dispersed throughout the polymer matrix. 
     
     
         14 . The nanoparticle of  claim 13 , wherein the therapeutic agent is docetaxel.