Exosomal formulation of anthocyanidins against multiple cancer types. (1st May 2017)

• Record Type: Journal Article
• 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.
• Is Part Of: Cancer letters. Volume 393(2017)
• Page Start: 94
• Page End: 102
• Publication Date: 2017-05-01
• Subjects: Milk exosomes -- Anthocyanidins -- Drug delivery -- Anti-cancer -- Anti-inflammatory; miRNA microRNA -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide -- AFM atomic force microscopy -- Anthos anthocyanidins -- ExoAnthos Exosomal formulation of Anthos -- Cy cyaniding -- Dp delphinidin -- Pt petunidin -- Pe peonidin -- Pg pelargonidin -- Mv malvidin -- EMSA Electrophoretic Mobility Shift Assay (EMSA) -- UPLC ultra high-performance liquid chromatography -- TNF-α tumor necrosis factor-α -- PDI poly dispersity index; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2017.02.004
• Languages: English
• ISSNs: 0304-3835

Abstract

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. Highlights: Milk exosomes can serve as a vehicle to berry bioactive, anthocyanidins (Anthos). Anthocyanidins were stable in exosomal formulation for weeks. Exosomes alone exhibited anti-proliferative and anti-inflammatory effects. Exosomal formulation of Anthos provide enhanced activity compared with free Anthos. Oral delivery of ExoAnthos caused significant inhibition of lung tumor xenografts.