System for Targeted Delivery of Therapeutic Agents

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.

1 . - 49 . (canceled) 
     
     
         50 . A targeted particle, comprising:
 a particle:   a targeting moiety: and   a therapeutic agent;   wherein the particle comprises a polymeric matrix, wherein the polymeric matrix comprises a polyester, and wherein the targeting moiety targets a target selected from the group consisting of prostate specific antigen, human glandular kallikrein 2, prostatic acid phosphatase, androgen receptor, insulinlike growth factor, insulin-like growth factor binding protein, transmembrane protein 24P4C12, prostate stem cell antigen, calveolin, PHOR-1, C-type lectin transmembrane antigen, protein encoded by 103P2D6, prostatic specific reductase polypeptide, and IL-11 receptor-a.   
     
     
         51 . (canceled) 
     
     
         52 . The targeted particle of  claim 50 , wherein the target is an endothelial cancer specific marker. 
     
     
         53 . The targeted particle of  claim 50 , wherein the target comprises a nucleic acid. 
     
     
         54 . The targeted particle of  claim 50 , wherein the target is a carbohydrate selected from the group consisting of glycoproteins, saccharides, and glycocalyx. 
     
     
         55 . The targeted particle of  claim 50 , wherein the specific binding of the targeting moiety to the target depends on the three dimensional characteristics of the targeting moiety. 
     
     
         56 . The targeted particle of  claim 50 , wherein the specific binding of the targeting moiety to the target depends on the three dimensional characteristics of the target. 
     
     
         57 . The targeted particle of  claim 50 , wherein the therapeutic agent is selected from the group consisting of small molecules, proteins, nucleic acids, carbohydrates, lipids, and combinations thereof. 
     
     
         58 . The targeted particle of  claim 50 , wherein the therapeutic agent is an anti-cancer agent. 
     
     
         59 . The targeted particle of  claim 50 , wherein the therapeutic agent is selected from the group consisting of antibodies, recombinant antibodies, humanized antibodies, characteristic portions thereof, and combinations thereof. 
     
     
         60 . The targeted particle of  claim 50 , wherein the therapeutic agent is an enzyme. 
     
     
         61 . The targeted particle of  claim 50 , wherein the therapeutic agent is a small interfering RNA, a small hairpin RNA, or a microRNA. 
     
     
         62 . The targeted particle of  claim 50 , wherein the therapeutic agent is a diagnostic agent. 
     
     
         63 . The targeted particle of  claim 62 , wherein the diagnostic agent is selected from the group consisting of fluorescent moieties, radionuclides, gases, anti-emetics, and contrast agents. 
     
     
         64 . The targeted particle of  claim 63 , wherein the radionuclide is selected from the group consisting of gamma-emitters, positron-emitters, X-ray emitters, beta-emitters, and alpha-emitters. 
     
     
         65 . The targeted particle of  claim 62 , wherein the diagnostic agent is an imaging agent used in positron emissions tomography (PET), computer assisted tomography (CAT), single photon emission computerized tomography, x-ray, fluoroscopy, or magnetic resonance imaging (MRI). 
     
     
         66 . The targeted particle of  claim 50 , wherein the therapeutic agent is a prophylactic agent. 
     
     
         67 . The targeted particle of  claim 66 , wherein the prophylactic agent is a vaccine. 
     
     
         68 . The targeted particle of  claim 50 , wherein the therapeutic agent is a nutraceutical agent. 
     
     
         69 . - 71 . (canceled) 
     
     
         72 . The targeted particle of  claim 50 , wherein the targeting moiety is associated with the surface of, encapsulated within, surrounded by, or dispersed throughout the particle. 
     
     
         73 . The targeted particle of  claim 50 , wherein the targeting moiety is associated with the particle via at least one covalent linkage. 
     
     
         74 . The targeted particle of  claim 73 , wherein the covalent linkage is mediated by an aliphatic or heteroaliphatic linker. 
     
     
         75 . The targeted particle of  claim 73 , wherein the covalent linkage is mediated by a polyether linker. 
     
     
         76 . The targeted particle of  claim 50 , wherein the therapeutic agent is associated with the particle. 
     
     
         77 . The targeted particle of  claim 50 , wherein the therapeutic agent is non-covalently associated with the particle. 
     
     
         78 . The targeted particle of  claim 50 , wherein the therapeutic agent is associated with the surface of, encapsulated within, surrounded by, or dispersed 
     
     
         79 . The targeted particle of  claim 50 , wherein the therapeutic agent is associated with the particle via at least one covalent linkage. 
     
     
         80 . The targeted particle of  claim 79 , wherein the covalent linkage is mediated by hydrocarbon linker. 
     
     
         81 . The targeted particle of  claim 79 , wherein the covalent linkage is mediated by a polyether linker. 
     
     
         82 . A pharmaceutical composition comprising the targeted particle of  claim 50  and a pharmaceutically acceptable excipient. 
     
     
         83 . A method of administering a targeted particle to a subject, comprising: providing a subject, wherein the subject comprises at least one cell; providing the targeted particle of  claim 50 ; and administering the targeted particle to the subject. 
     
     
         84 . - 87 . (canceled) 
     
     
         88 . The method of  claim 83 , wherein particles are manufactured by nanoprecipitation. 
     
     
         89 . The method of  claim 83 , wherein particles are manufactured by flow focusing using fluidic channels. 
     
     
         90 . The method of  claim 83 , wherein particles of a predetermined size are isolated using a sieve. 
     
     
         91 . The method of  claim 83 , wherein the targeted particle is administered to the subject by an oral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal, interdermal, rectal, intravaginal, intraperitoneal, topical, transdermal, mucosal, nasal, buccal, enteral, or sublingual route. 
     
     
         92 . The method of  claim 83 , wherein the targeted particle is administered to the subject orally, intravenously, or parenterally. 
     
     
         93 . The method of  claim 83 , wherein the targeted particle is administered to the subject by intratracheal instillation, bronchial instillation, or inhalation. 
     
     
         94 . The method of  claim 83 , wherein the targeted particle is administered to the subject as an oral spray, nasal spray, or aerosol. 
     
     
         95 . The method of  claim 83 , wherein the targeted particle is administered directly to the prostate. 
     
     
         96 . The method of  claim 83 , wherein the targeted particle is administered directly to prostate cancer cells. 
     
     
         97 . - 98 . (canceled) 
     
     
         99 . The method of  claim 83 , wherein the targeted particle is administered to the subject by implantation of targeted particles at or near prostate cancer cells by stereotactic surgery. 
     
     
         100 . The method of  claim 83 , wherein the targeted particle is administered to the subject by implantation of targeted particles at or near prostate cancer cells during surgical removal of a tumor. 
     
     
         101 . - 105 . (canceled)