Core-shell particle formulation for delivering multiple therapeutic agents

Abstract

A core-shell particle formulation for delivering multiple therapeutic agents is disclosed. More particularly, the formulation comprising protein-protein core-shell particle configured to independently release therapeutic agents from the core and the shell. Moreover, the core-shell particle bearing therapeutic agents enable treatment against the diseases such as cancer, inflammatory and auto-immune diseases.

What is claimed is: 
     
         1 . A core-shell particle formulation for delivering multiple therapeutic agents comprising:
 a protein core comprising a first protein loaded with a first therapeutic agent; and   a protein shell encapsulating the core to form a particle formulation, wherein the protein shell comprises a cross-linked second protein loaded with a second therapeutic agent;   wherein the particle is configured to independently release the therapeutic agents from the core and the shell.   
     
     
         2 . The formulation of  claim 1 , wherein the size of the core-shell particle is 1-1000 nm. 
     
     
         3 . The formulation of  claim 1 , wherein the first protein or the second protein comprises human serum albumin, bovine serum albumin, protamine, transferrin, lactoferrin, fibrinogen, gelatin, mucin, soy protein, apoferritin, ferritin, lectin, gluten, whey protein, prolamines, gliadin, hordein, secalin, zein, avenin, or combinations thereof. 
     
     
         4 . The formulation of  claim 1 , wherein the first therapeutic agent or the second therapeutic agent comprises cytotoxic drugs, small molecule kinase inhibitors, phytochemicals, deoxyribozymes, ribozymes, siRNA, shRNA, DNA, PNAs, miRNAs, or combinations thereof. 
     
     
         5 . The formulation of  claim 1 , wherein the first therapeutic agent or the second therapeutic agent comprises demethylation agents, retinoids, antimetabolites, anti microtubule agents, anti-angiogenesis agents, alkylating agents, biologic response modifiers, antitumor antibiotics, proteasome inhibitors, topoisomerase I inhibitors, hormones, immunomodulators, monoclonal antibodies, aromatase inhibitors, glucocorticosteroids, cytokines, enzymes, anti-androgen molecules, epigenetic modifiers, imatinib, sorafenib, nilotinib, erlotinib, gefitinib, dasatinib, everolimus, or combinations thereof. 
     
     
         6 . The formulation of  claim 1 , wherein the core or the shell or both are embedded with metallic nanoclusters comprising one or more of gold, silver, platinum, copper, or iron. 
     
     
         7 . The formulation of  claim 1 , wherein the therapeutic agents are configured to be delivered by passive targeting. 
     
     
         8 . The formulation of  claim 7 , wherein the therapeutic agents are configured to be delivered from the shell and core sequentially. 
     
     
         9 . The formulation of  claim 7 , wherein the therapeutic agents are configured to be delivered from the shell and core simultaneously. 
     
     
         10 . The formulation of  claim 1 , wherein the therapeutic agents are configured to be delivered by active targeting. 
     
     
         11 . The formulation of  claim 8 , wherein the therapeutic agents are configured to be delivered from the shell and core sequentially. 
     
     
         12 . The formulation of  claim 8 , wherein the therapeutic agents are configured to be delivered from the shell and core simultaneously. 
     
     
         13 . The formulation of  claim 8 , wherein the active targeting is achieved by conjugating the core-shell formulation with monoclonal antibody against CD20, CD33, CD34, CD38, CD44, CD47, CD52 CD90, CD 123, CD 133, EGFR, PDGFR, VEGF, HER2, mTOR, PI3K-Akt, BCR-ABL, SRC, STAT5, MAPK, HER2, transferrin receptors, R.GD, CRGD, LyP-1, bombesin, FSH33, truncated human basic fibroblast growth factor, octreotide, folic acid, mannose, hyaluronic acid, transferrin, somatostatin, or aptamers. 
     
     
         14 . A method of treating a disease, condition or disorder comprising:
 administering to a human patient a therapeutically effective amount of a core-shell particle formulation comprising a protein core comprising a first protein loaded with a first therapeutic agent; and a protein shell encapsulating the core to form a particle formulation, wherein the protein shell comprises a cross-linked second protein loaded with a second therapeutic agent; wherein the particle is configured to independently release the therapeutic agents from the core and the shell;   wherein the core-shell particle formulation is administered by local injection, intravenous, subcutaneous, intramuscular or oral delivery.   
     
     
         15 . The method of  claim 14 , further comprising passively targeting a targeted tissue with the therapeutic agents. 
     
     
         16 . The method of  claim 14 , further comprising actively targeting a targeted tissue with the therapeutic agents. 
     
     
         17 . The method of  claim 16 , further comprising sequentially delivering the therapeutic agents from the shell and core to the targeted tissue. 
     
     
         18 . The method of  claim 16 , further comprising simultaneously delivering the therapeutic agents from the shell and core to the targeted tissue. 
     
     
         19 . The method of  claim 14 , wherein the treatment comprises anticancer therapy, anti-inflammatory therapy, or immunotherapy.