title: Exosomal formulation of anthocyanidins against multiple cancer types.
abstract: Over the last two decades, berries and berry bioactives, particularly anthocyanins and their aglycones anthocyanidins (Anthos) have demonstrated excellent anti-oxidant, anti-proliferative, apoptotic and anti-inflammatory properties. However, their physicochemical and pharmacokinetic limitations such as, low permeability, and poor oral bioavailability are considered as unfavorable properties for development as drugs. Therefore there is a need to develop systems for efficient systemic delivery and robust bioavailability. In this study we prepared nano-formulation of bilberry-derived Anthos using exosomes harvested from raw bovine milk. Exosomal formulation of Anthos enhanced antiproliferative and anti-inflammatory effects compared with the free Anthos against various cancer cells in vitro. Our data also showed significantly enhanced therapeutic response of exosomal-Anthos formulation compared with the free Anthos against lung cancer tumor xenograft in nude mice. The Anthos showed no signs of gross or systemic toxicity in wild-type mice. Thus, exosomes provide an effective alternative for oral delivery of Anthos that is efficacious, cost-effective, and safe, and this regimen can be developed as a non-toxic, widely applicable therapeutic agent.
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA; Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Radha
authors.initials: R
authors.lastname: Munagala
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA; Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Farrukh
authors.initials: F
authors.lastname: Aqil
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Jeyaprakash
authors.initials: J
authors.lastname: Jeyabalan
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Agrawal
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Mudd
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Al Hassan
authors.initials: AH
authors.lastname: Kyakulaga
authors.affiliation: National Institute of Pharmaceutical Education and Research, S.A.S Nagar, India.
authors.forename: Inder P
authors.initials: IP
authors.lastname: Singh
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Manicka V
authors.initials: MV
authors.lastname: Vadhanam
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA. Electronic address: rcgupta@louisville.edu.
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
mesh_terms: D000072283:A549 Cells; D000284:Administration, Oral; D000818:Animals; D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D055354:Exosomes / Q000737:chemistry*; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D008819:Mice, Nude; D008892:Milk / Q000737:chemistry* / Q000633:toxicity; D053758:Nanoparticles; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000872:Anthocyanins; D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers
keywords: Anthocyanidins; Anti-cancer; Anti-inflammatory; Drug delivery; Milk exosomes