Milk-Derived Microvesicle Compositions and Related Methods

Abstract

A composition is provided that comprises a therapeutic agent encapsulated by a milk-derived microvesicle. The compositions can include therapeutic agents such as phytochemical agents or chemotherapeutic agents, while the milk-derived microvesicle can be derived from raw milk or colostrum. Further provided are methods for isolating a microvesicle that includes the steps of obtaining an amount of milk, and subjecting the milk to a series of sequential centrifugations configured to yield greater than about 300 mg of microvesicle protein per 100 ml of milk. Methods of modifying an immune response and treating a cancer in which a milk-derived microvesicle composition is administered are also provided.

What is claimed is: 
     
         1 . A composition comprising an effective amount of a therapeutic agent encapsulated by a milk-derived microvesicle, wherein the therapeutic agent is a nucleic acid. 
     
     
         2 . The composition of  claim 1  wherein the nucleic acid is a ribonucleic acid (RNA) molecule. 
     
     
         3 . The composition of  claim 2  wherein the RNA molecule comprises one or more non-naturally occurring modifications. 
     
     
         4 . The composition of  claim 2  wherein the RNA molecule is a non-coding RNA. 
     
     
         5 . The composition of  claim 2  or  claim 3  wherein the RNA molecule is a miRNA molecule. 
     
     
         6 . The composition of  claim 5  wherein the miRNA molecule is selected from miR-155, miR-223 or a combination thereof. 
     
     
         7 . The composition of  claim 3  wherein the RNA molecule is a siRNA molecule. 
     
     
         8 . The composition of  claim 2  or  claim 3 , wherein the RNA molecule is a messenger RNA (mRNA) molecule. 
     
     
         9 . The composition of  claim 1  or  2  wherein the milk is raw milk or colostrum. 
     
     
         10 . The composition of  claim 9  wherein the raw milk is bovine raw milk. 
     
     
         11 . The composition of  claim 9  wherein the colostrum is bovine colostrum. 
     
     
         12 . The composition of  claim 1  or  2  wherein the therapeutic agent loading is from 3.8% to 65%. 
     
     
         13 . The composition of  claim 1  or  2 , further comprising a pharmaceutically-acceptable vehicle, carrier, or excipient. 
     
     
         14 . A method of modifying an immune response, comprising administering to a subject in need thereof an effective amount of a composition of any of  claims 1 - 13 . 
     
     
         15 . A method of modifying an immune response, comprising administering to a subject in need thereof an effective amount of a composition comprising an effective amount of a therapeutic agent encapsulated by a milk-derived microvesicle, wherein the therapeutic agent is selected from miR-155, miR-223 or a combination thereof. 
     
     
         16 . Method of treating cancer, comprising administering to a subject in need thereof an effective amount composition of of any of  claims 1 - 13 . 
     
     
         17 . The method of  claim 15 , wherein the cancer is selected from the group consisting of lung, breast, cervical, ovarian, prostate, and pancreatic cancer. 
     
     
         18 . A method of treating an inflammatory disorder, comprising administering an effective amount of a composition of any of  claims 1 - 13  to a subject in need of treatment for an inflammatory disorder. 
     
     
         19 . The method of  claim 17 , wherein the inflammatory disorder selected from the group consisting of atherosclerosis; arthritis; inflammation-promoted cancers; asthma; autoimmune uveitis; adoptive immune response; dermatitis; multiple sclerosis; diabetic complications; osteoporosis; Alzheimer's disease; cerebral malaria; hemorrhagic fever; autoimmune disorders; and inflammatory bowel disease.