Exosomal formulation of anthocyanidins against multiple cancer types

• Published in: Cancer letters Vol. 393; pp. 94 - 102
• Main Authors: Munagala, Radha, Aqil, Farrukh, Jeyabalan, Jeyaprakash, Agrawal, Ashish K, Mudd, Ashley M, Kyakulaga, Al Hassan, Singh, Inder P, Vadhanam, Manicka V, Gupta, Ramesh C
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.05.2017; Elsevier Limited
• Subjects: A549 Cells; Administration, Oral; Animals; Anthocyanidins; Anthocyanins - chemistry; Anthocyanins - pharmacology; Anti-cancer; Anti-inflammatory; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Awards & honors; Bioavailability; Cancer therapies; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Carriers; Drug Compounding; Drug delivery; Exosomes - chemistry; Female; HCT116 Cells; Hematology, Oncology and Palliative Medicine; Humans; Laboratories; Male; MCF-7 Cells; Mice, Nude; Milk - chemistry; Milk - toxicity; Milk exosomes; Nanoparticles; Studies; Sugar; Time Factors; Toxicity; Tumor Burden - drug effects; Xenograft Model Antitumor Assays; Exosomal formulation of Anthos; malvidin; AFM; Mv; Drug delivery; Anthos; Anthocyanidins; MTT; delphinidin; pelargonidin; PDI; Pe; Cy; peonidin; EMSA; Pg; miRNA; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; high-performance liquid chromatography; Anti-cancer; Milk exosomes; HPLC; ExoAnthos; Pt; cyaniding; Electrophoretic Mobility Shift Assay (EMSA); atomic force microscopy; Dp; poly dispersity index; TNF-α; tumor necrosis factor-α; petunidin; microRNA; Anti-inflammatory; UPLC
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2017.02.004

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 solubility, 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. To overcome this barrier, 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.