title: Bovine milk-derived exosomes for drug delivery.
abstract: Exosomes are biological nanovesicles that are involved in cell-cell communication via the functionally-active cargo (such as miRNA, mRNA, DNA and proteins). Because of their nanosize, exosomes are explored as nanodevices for the development of new therapeutic applications. However, bulk, safe and cost-effective production of exosomes is not available. Here, we show that bovine milk can serve as a scalable source of exosomes that can act as a carrier for chemotherapeutic/chemopreventive agents. Drug-loaded exosomes showed significantly higher efficacy compared to free drug in cell culture studies and against lung tumor xenografts in vivo. Moreover, tumor targeting ligands such as folate increased cancer-cell targeting of the exosomes resulting in enhanced tumor reduction. Milk exosomes exhibited cross-species tolerance with no adverse immune and inflammatory response. Thus, we show the versatility of milk exosomes with respect to the cargo it can carry and ability to achieve tumor targetability. This is the first report to identify a biocompatible and cost-effective means of exosomes to enhance oral bioavailability, improve efficacy and safety of drugs.
authors.affiliation: Department of Medicine, University of Louisville, Louisville, KY 40202.|James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202.
authors.forename: Radha
authors.initials: R
authors.lastname: Munagala
authors.affiliation: Department of Medicine, University of Louisville, Louisville, KY 40202.|James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202.
authors.forename: Farrukh
authors.initials: F
authors.lastname: Aqil
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202.
authors.forename: Jeyaprakash
authors.initials: J
authors.lastname: Jeyabalan
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202.|Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202.
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D055354:Exosomes / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D008892:Milk / Q000276:immunology / Q000378:metabolism* / Q000633:toxicity; D053758:Nanoparticles; D012995:Solubility; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D004337:Drug Carriers; D005492:Folic Acid
keywords: Chemopreventive agents; Chemotherapeutic drugs; Drug delivery; Milk-derived exosomes; Tumor-targeting