Liposome for liver-specific delivery and release of therapeutic nucleic acids or drugs
Disclosed herein is a composite of a nanoscale particle size. The composite is able to specifically deliver therapeutic agents such as therapeutic nucleic acids or drugs to the liver and selectively release them into hepatic cells to manifest potent therapeutic effects of the therapeutic agents. The composite may be comprised of an apolipoprotein A-1 and a liposome-forming material. A composition containing the composite and a pharmaceutically acceptable carrier is disclosed.
1. A composition comprising:
an isolated composite of an apolipoprotein A-1 and a liposome-forming material, said liposome-forming material being a mixture of 1,2-dioleoyl-3-trimethylammonium-propane and cholesterol, forming a liposome;
a pharmaceutically acceptable carrier; and
an isolated therapeutic agent which is targeted to be delivered to and released in the liver of a subject who is in need of receiving the therapeutic agent, encapsulated within the liposome.
2. The composition according to claim 1 , wherein the therapeutic agent is a therapeutic nucleic acid.
3. The composition according to claim 2 , wherein the therapeutic nucleic acid is an siRNA specific for HBV or HCV genome.
4. The composition according to claim 1 , wherein the weight ratio of the apolipoprotein A-1 and the liposome-forming material is in the range of 1: 0.1 to 1: 1000.
5. The composition according to claim 1 , wherein the therapeutic agent is an active polypeptide, an anticancer agent or an antivirus agent.
6. The composition according to claim 5 , wherein the active polypeptide is selected from the group consisting of epidermal growth factor, erythropoietin, coagulation factors VIII, IX and VIIa, follicle stimulating hormone, granulocyte colony-stimulating factor, granulocyte-macrophage colony stimulating factor, insulin, insulin-like growth factor, interferon-α, -β and -γ, interleukin-1, -2, -11, -12 and -15, parathyroid hormone, platelet-derived growth factor, human growth hormone, tissue plasminogen activator, vascular endothelial growth factor, and a mixture thereof.
7. The composition according to claim 5 , 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, fluoxuridine, mitomycin, bleomycin, clofazimine, interferon, streptozocin, gemcitabine, enocitabine, capecitabine, ursodeoxycholic acid, sorafenib, tegafur, holmium, a holmium-chitosan complex, and a mixture thereof.
8. The composition according to claim 5 , 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.