System for targeted delivery of therapeutic agents
First Claim
1. A targeted particle comprising polymer conjugated to a surfactant, hydrophilic polymer or lipid,the particle having bound thereto a plurality of small molecule targeting moieties that specifically bind to the Zn2+ NAAG/PSMA binding pocket within prostate specific membrane antigen (PSMA) selected from the group consisting of 2-PMPA, GPI5232, VA-033 2MPPA, thiol and indole thiol based PSMA inhibitors, 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acid derivative PSMA inhibitors, hydroxamate derivative PSMA inhibitors, PDBA-based PSMA inhibitors, and urea-based PSMA inhibitors, andhaving encapsulated or dispersed therein a therapeutic, diagnostic or prophylactic agent,wherein at least 80% of the particles have a greatest dimension less than 250 nm and have enhanced permeation through tumor vasculature and retention in tumor tissue as compared to particles greater than 250 nm.
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Abstract
The present invention provides a drug delivery system for targeted delivery of therapeutic agent-containing particles to tissues, cells, and intracellular compartments. The invention provides targeted particles comprising a particle, one or more targeting moieties, and one or more therapeutic agents to be delivered and pharmaceutical compositions comprising inventive targeted particles. The present invention provides methods of designing, manufacturing, and using inventive targeted particles and pharmaceutical compositions thereof.
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Citations
43 Claims
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1. A targeted particle comprising polymer conjugated to a surfactant, hydrophilic polymer or lipid,
the particle having bound thereto a plurality of small molecule targeting moieties that specifically bind to the Zn2+ NAAG/PSMA binding pocket within prostate specific membrane antigen (PSMA) selected from the group consisting of 2-PMPA, GPI5232, VA-033 2MPPA, thiol and indole thiol based PSMA inhibitors, 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acid derivative PSMA inhibitors, hydroxamate derivative PSMA inhibitors, PDBA-based PSMA inhibitors, and urea-based PSMA inhibitors, and having encapsulated or dispersed therein a therapeutic, diagnostic or prophylactic agent, wherein at least 80% of the particles have a greatest dimension less than 250 nm and have enhanced permeation through tumor vasculature and retention in tumor tissue as compared to particles greater than 250 nm.
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22. A method of treating prostate cancer in a subject, comprising administering an effective amount to a subject in need thereof of particles comprising polymer conjugated to a surfactant, hydrophilic polymer or lipid,
the particle having bound thereto a plurality of small molecule targeting moieties that specifically bind to the Zn2+ NAAG/PSMA binding pocket within prostate specific membrane antigen (PSMA) selected from the group consisting of 2-PMPA, GPI5232, VA-033, thiol and indole thiol based PSMA inhibitors, 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acid derivative PSMA inhibitors, hydroxamate derivative PSMA inhibitors, PDBA-based PSMA inhibitors, and urea-based PSMA inhibitors, having encapsulated or dispersed therein a therapeutic, diagnostic or prophylactic agent, wherein at least 80% of the particles have a greatest dimension less than 250 nm and have enhanced permeation through tumor vasculature and retention in tumor tissue as compared to particles greater than 250 nm.
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31. A method of preparing particles comprising polymer conjugated to a surfactant, hydrophilic polymer or lipid,
the particle having bound thereto a plurality of protein or small molecule targeting moieties that specifically bind to the particle having bound thereto a plurality of small molecule targeting moieties that specifically bind to the Zn2+ NAAG/PSMA binding pocket within prostate specific membrane antigen (PSMA) selected from the group consisting of 2-PMPA, GPI5232, VA-033, thiol and indole thiol based PSMA inhibitors, 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acid derivative PSMA inhibitors, hydroxamate derivative PSMA inhibitors, PDBA-based PSMA inhibitors, and urea-based PSMA inhibitors, and having encapsulated or dispersed therein a therapeutic, diagnostic or prophylactic agent, wherein at least 80% of the particles have a greatest dimension less than 250 nm and have enhanced permeation through tumor vasculature and retention in tumor tissue as compared to particles greater than 250 nm, comprising nanoprecipitation or flow focusing fluidic channels of polymer conjugated to a surfactant, hydrophilic polymer or lipid, in combination with a therapeutic, diagnostic or prophylactic agent and targeting moieties that specifically binding to prostate specific membrane antigen selected from the group consisting of 2-PMPA, GPI5232, VA-033, thiol and indole thiol based PSMA inhibitors, 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acid derivative PSMA inhibitors, hydroxamate derivative PSMA inhibitors, PDBA-based PSMA inhibitors, and urea-based PSMA inhibitors, and selecting the particles having a greatest dimension less than 250 nm.
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32. A population of targeted particles, comprising
a particle comprising a polymeric matrix, wherein the polymeric matrix comprises a polyester; -
a targeting moiety wherein the targeting moiety is a urea-based prostate specific membrane antigen (PSMA) inhibitor; and a therapeutic agent; wherein at least 80% of the particles have a greatest dimension less than 250 nm, having encapsulated or dispersed therein a therapeutic, diagnostic or prophylactic agent, and having enhanced permeation through tumor vasculature and retention in tumor tissue as compared to particles greater than 250 nm. - View Dependent Claims (33, 38, 41, 42)
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Specification