Curcumin Encapsulated in Milk Exosomes Resists Human Digestion and Possesses Enhanced Intestinal Permeability in Vitro

Abstract

Exosomes, the extracellular secretary nano-vesicles, act as carriers of biomolecules to the target cells. They exhibit several attributes of an efficient drug delivery system. Curcumin, despite having numerous bioactive and therapeutic properties, has limited pharmaceutical use due to its poor water solubility, stability, and low systemic bioavailability. Hence, this study aims to enhance the therapeutic potential of curcumin, a model hydrophobic drug, by its encapsulation into milk exosomes. In the present study, we investigated the stability of free curcumin and exosomal curcumin in PBS and in vitro digestive processes. Additionally, their uptake and trans-epithelial transport were studied on Caco-2 cells. Curcumin in milk exosomes had higher stability in PBS, sustained harsh digestive processes, and crossed the intestinal barrier than free curcumin. In conclusion, the encapsulation of curcumin into the exosomes enhances its stability, solubility, and bioavailability. Therefore, the present study demonstrated that milk exosomes act as stable oral drug delivery vehicles.

Milk MicroRNAs in Health and Disease

“…Milk EVs have been extensively studied for their biological functions upon consumption (Agrawal et al., ; Aqil et al., ; Aqil, Munagala, Jeyabalan, Agrawal, & Gupta, ; Arntz et al., ; Badawy, El‐Magd, & AlSadrah, ; Leiferman et al., ; Matsuda & Patel, ; Munagala, Aqil, Jeyabalan, & Gupta, ; Munagala et al., ; Oliveira et al., , 2017) and numerous studies have reported that milk EVs are bioaccessible (survive digestion; Benmoussa et al., ; Kahn et al., ; Liao et al., ; Rani et al., ; Shandilya, Rani, Onteru, & Singh, ; Vashisht, Rani, Onteru, & Singh, ) and bioavailable (Le Doare et al., ; Wang et al., ; Zempleni, ; Zempleni et al., ).…”

“…According to more than 30 studies, from different teams around the world, milk EVs resisted in vitro digestion (Benmoussa et al., ; Kahn et al., ; Liao et al., ; Rani et al., ; Shandilya et al., ; Vashisht et al., ) were internalized by recipient cells upon co‐incubation (Admyre et al., , 2008; Aqil et al., , ; Badawy et al., ; Golan‐Gerstl et al., ; Hock et al., ; Kahn et al., ; Liao et al., ; Maburutse, Park, Oh, & Kim, ; Martin et al., ; Matsuda & Patel, ; Mobley et al., ; Munagala et al., ; Naslund et al., ; Qin et al., ; Vashisht, Rani, Onteru, & Singh, ; Yu et al., ), transduced through the intestinal wall in vitro (Rani et al., ; Shandilya et al., ; Wolf et al., ), and were detected in animal models after ingestion (Manca et al., ; Munagala et al., ) or intravenous injection (Somiya, Yoshioka, & Ochiya, ).…”

“…Twenty‐one studies involving milk EVs from humans, rat, camels, and most often cow milks reported milk EVs bioactivity in vitro on cells (Admyre et al., ; Aqil et al., , ; Badawy et al., ; Golan‐Gerstl et al., ; Hock et al., ; Martin et al., ; Matsuda & Patel, ; Mobley et al., ; Munagala et al., ; Naslund et al., ; Qin et al., ; Vashisht et al., ; Yu et al., ) and in vivo in animal models (Agrawal et al., ; Aqil et al., , ; Badawy et al., ; Leiferman et al., ; Munagala et al., ; Munagala et al., ; Somiya et al., ).…”

“…Functionality of milk EVs has been explored following their intrinsic biological activity or their potential as drug carriers for cancer treatment (Agrawal et al., ; Aqil et al., , ; Badawy et al., ; Munagala et al., , ; Qin et al., ; Somiya et al., ), for the modulation of inflammation (Admyre et al., ; Arntz et al., ; Badawy et al., ; Martin et al., ; Vashisht et al., ), for gut, bone, and muscle development (Chen et al., ; Hock et al., ; Leiferman et al., ; Martin et al., ; Mobley et al., ; Oliveira et al., , ), bacterial proliferation (Yu et al., ), and in the prevention of HIV infection (Naslund et al., ).…”

Diet and cancer prevention: Dietary compounds, dietary MicroRNAs, and dietary exosomes

“…Recent efforts have been undertaken to use milk‐derived exosomes foe the encapsulation curcumin which could enhance curcumin transport and drug effects. These results suggested that using milk‐derived exosomes containing curcumin could induce therapeutic effects of curcumin in the better way than using curcumin alone …”