Long circulating nanoparticles for sustained release of therapeutic agents

摘要

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.

主权项

1. A sterile, biocompatible, injectable nanoparticle composition comprising a plurality of long circulating nanoparticles having a diameter of about 70 to about 130 nm, each of the plurality of the long circulating nanoparticles comprising:
about 70 to about 90 weight percent poly(lactic) acid-co-poly(ethylene) glycol, wherein the weight ratio of poly(lactic) acid to poly(ethylene) glycol is about 15 kDa/2 kDa to about 20 kDa/10 kDa, and a therapeutic agent encapsulated in the nanoparticles,said composition providing an elevated plasma concentration of the therapeutic agent for at least 24 hours when the composition is administered to a patient, to provide:an area under the plasma concentration time curve (AUC) that is increased by at least 500% over the AUC provided when the equivalent dosage of the therapeutic agent is intravenously administered in a non-nanoparticle to a patient;an actual peak plasma concentration (Cmax) that is at least 100% higher as compared to a Cmax of said therapeutic when the therapeutic agent is intravenously administered in a non-nanoparticle to the patient; anda volume of distribution (Vz) that is about the patient's plasma volume upon intravenous administration of the composition.