Composite For Liver-Specific Delivery and Release of Therapeutic Nucleic Acids or Drugs

Abstract

The inventive composite having a nanoscale particle size can specifically deliver therapeutic nucleic acids or drugs to the liver and selectively release them into hepatic cells to manifest potent therapeutic effects without inducing any enzymatic abnormalities or pathological damage to the normal liver function, when administered together with the therapeutic agents.

1 . A composite comprising an apolipoprotein A-I and a liposome-forming material. 
     
     
         2 . The composite of  claim 1 , wherein the liposome-forming material is a cationic or neutral liposome-forming material, or a mixture of thereof. 
     
     
         3 . The composite of  claim 2 , wherein the cationic liposome-forming material is selected from the group consisting of DOTAP (1,2-dioleoyl-3-trimethylammonium-propane), DC-cholosterol (3β-[N-(N′,N′-dimethylaminoethane)carbamyl]cholesterol), DDAB (dimethyldioctadecylammonium bromide), and a mixture thereof. 
     
     
         4 . The composite of  claim 2 , wherein the neutral liposome-forming material is selected from the group consisting of DOPE (L-alpha-dioleoyl phosphatidylethanolamine), cholesterol, and a mixture thereof. 
     
     
         5 . The composite of  claim 1 , wherein the weight ratio of the apolipoprotein A-I and the liposome-forming material is in the range of 1:0.1 to 1:1000. 
     
     
         6 . The composite of  claim 1 , which further comprise a therapeutic nucleic acid or a drug. 
     
     
         7 . The composite of  claim 6 , wherein the therapeutic nucleic acid is selected from the group consisting of a DNA, an RNA, and a derivative thereof. 
     
     
         8 . The composite of  claim 7 , wherein the RNA is an siRNA specific for HBV or HCV genome. 
     
     
         9 . The composite of  claim 6 , wherein the therapeutic drug is an active polypeptide, an anticancer agent or an antivirus agent. 
     
     
         10 . The composite of  claim 9 , wherein the active polypeptide is selected from the group consisting of epidermal growth factor (EGF), erythropoietin (EPO), coagulation factors VIII, IX and VIIa, follicle stimulating hormone (FSH), granulocyte colony-stimulating factor (GCSF), granulocyte-macrophage colony stimulating factor (GM-CSF), insulin, insulin-like growth factor (IGF), interferon-α, -β and -γ (IFN-α, -β and -γ), interleukin-1, -2, -11, -12 and -15 (IL-1, -2, -11, -12 and -15), parathyroid hormone (PTH), platelet-derived growth factor (PDGF), human growth hormone (hGH), tissue plasminogen activator (tPA), vascular endothelial growth factor (VEGF), and a mixture thereof. 
     
     
         11 . The composite of  claim 9 , wherein the anticancer agent is selected from the group consisting of carboplatin, cisplatin, oxaliplatin, heptaplatin, etoposide, semustine, hydroxycarbamide, citarabine, fludarabine, doxorubicin, epirubicin, idarubicin, pirarubicin, fluorouracil (5-FU), fluoxuridine, mitomycin, bleomycin, clofazimine, interferon, streptozocin, gemcitabine, enocitabine, capecitabine, ursodeoxycholic acid, sorafenib, tegafur, holmium, a holmium-chitosan complex, and a mixture thereof. 
     
     
         12 . The composite of  claim 9 , wherein the antivirus agent is selected from the group consisting of atazanavir, ribavirin, zanamivir, acyclovir, entecavir, didanosin, nevirapine, valaciclovir, nelfinavir, efavirenz, ganciclovir, lamivudine, famciclovir, stavudine, abacavir, indinavir, oseltamivir, inosiplex, adefovir, and a mixture thereof. 
     
     
         13 . A composition comprising the composite of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         14 . The composition of  claim 13 , which further comprise a therapeutic nucleic acid or a drug. 
     
     
         15 . The composition of  claim 14 , wherein the therapeutic nucleic acid is selected from the group consisting of a DNA, an RNA, and a derivative thereof. 
     
     
         16 . The composition of  claim 15 , wherein the RNA is an siRNA specific for HBV or HCV genome. 
     
     
         17 . The composition of  claim 14 , wherein the therapeutic drug is an active polypeptide, an anticancer agent or an antivirus agent. 
     
     
         18 . The composition of  claim 17 , wherein the active polypeptide is selected from the group consisting of epidermal growth factor (EGF), erythropoietin (EPO), coagulation factors VIII, IX and VIIa, follicle stimulating hormone (FSH), granulocyte colony-stimulating factor (GCSF), granulocyte-macrophage colony stimulating factor (GM-CSF), insulin, insulin-like growth factor (IGF), interferon-α, -β and -γ (IFN-α, -β and -γ), interleukin-1, -2, -11, -12 and -15 (IL-1, -2, -11, -12 and -15), parathyroid hormone (PTH), platelet-derived growth factor (PDGF), human growth hormone (hGH), tissue plasminogen activator (tPA), vascular endothelial growth factor (VEGF), and a mixture thereof. 
     
     
         19 . The composition of  claim 17 , wherein the anticancer agent is selected from the group consisting of carboplatin, cisplatin, oxaliplatin, heptaplatin, etoposide, semustine, hydroxycarbamide, citarabine, fludarabine, doxorubicin, epirubicin, idarubicin, pirarubicin, fluorouracil (5-FU), fluoxuridine, mitomycin, bleomycin, clofazimine, interferon, streptozocin, gemcitabine, enocitabine, capecitabine, ursodeoxycholic acid, sorafenib, tegafur, holmium, a holmium-chitosan complex, and a mixture thereof. 
     
     
         20 . The composition of  claim 17 , wherein the antivirus agent is selected from the group consisting of atazanavir, ribavirin, zanamivir, acyclovir, entecavir, didanosin, nevirapine, valaciclovir, nelfinavir, efavirenz, ganciclovir, lamivudine, famciclovir, stavudine, abacavir, indinavir, oseltamivir, inosiplex, adefovir, and a mixture thereof.