title: Milk-derived exosomes for oral delivery of paclitaxel.
abstract: In this report milk-derived exosomes have been investigated for oral delivery of the chemotherapeutic drug paclitaxel (PAC) as an alternative to conventional i.v. therapy for improved efficacy and reduced toxicity. PAC-loaded exosomes (ExoPAC) were found to have a particle size of ~108 nm, a narrow particle size distribution (PDI ~0.190), zeta potential (~ -7 mV) and a practical loading efficiency of ~8%. Exosomes and ExoPAC exhibited excellent stability in the presence of simulated-gastrointestinal fluids, and during the storage at -80 °C. A sustained release of PAC was also observed up to 48 h in vitro using PBS (pH 6.8). Importantly, ExoPAC delivered orally showed significant tumor growth inhibition (60%; P<0.001) against human lung tumor xenografts in nude mice. Treatment with i.p. PAC at the same dose as ExoPAC, however, showed modest but statistically insignificant inhibition (31%). Moreover, ExoPAC demonstrated remarkably lower systemic and immunologic toxicities as compared to i.v. PAC.
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY.
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Agrawal
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY; Department of Medicine, University of Louisville, Louisville, KY.
authors.forename: Farrukh
authors.initials: F
authors.lastname: Aqil
authors.affiliation: Department of Medicine, University of Louisville, Louisville, KY.
authors.forename: Jeyaprakash
authors.initials: J
authors.lastname: Jeyabalan
authors.affiliation: 3P Biotechnologies, Inc., Louisville, KY.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Spencer
authors.affiliation: 3P Biotechnologies, Inc., Louisville, KY.
authors.forename: Joshua
authors.initials: J
authors.lastname: Beck
authors.affiliation: Department of Microbiology, Immunology & Molecular Genetics, and Markey Cancer Center, University of Kentucky, Lexington, KY.
authors.forename: Beth W
authors.initials: BW
authors.lastname: Gachuki
authors.affiliation: Department of Microbiology, Immunology & Molecular Genetics, and Markey Cancer Center, University of Kentucky, Lexington, KY.
authors.forename: Sara S
authors.initials: SS
authors.lastname: Alhakeem
authors.affiliation: Department of Microbiology, Immunology & Molecular Genetics, and Markey Cancer Center, University of Kentucky, Lexington, KY.
authors.forename: Karine
authors.initials: K
authors.lastname: Oben
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY; Department of Medicine, University of Louisville, Louisville, KY.
authors.forename: Radha
authors.initials: R
authors.lastname: Munagala
authors.affiliation: Department of Microbiology, Immunology & Molecular Genetics, and Markey Cancer Center, University of Kentucky, Lexington, KY.
authors.forename: Subbarao
authors.initials: S
authors.lastname: Bondada
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY; 3P Biotechnologies, Inc., Louisville, KY; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY. Electronic address: rcgupta@louisville.edu.
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D055354:Exosomes; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D008892:Milk; D017239:Paclitaxel / Q000008:administration & dosage*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel
keywords: Antitumor efficacy; Exosomes; Immunological responses; Lung cancer; Systemic toxicity; Taxol