Milk exosomes anchored with hydrophilic and zwitterionic motifs enhance mucus permeability for applications in oral gene delivery.

Exosomes have emerged as a promising tool for the delivery of drugs and genetic materials, owing to their biocompatibility and non-immunogenic nature. However, challenges persist in achieving successful oral delivery due to their susceptibility to degradation in the harsh gastrointestinal (GI) environment and impeded transport across the mucus-epithelium barrier. To overcome these challenges, we have developed high-purity bovine milk exosomes (mExo) as a scalable and efficient oral drug delivery system, which can be customized by incorporating hydrophilic and zwitterionic motifs on their surface.

Modeling Electrostatic Charge Shielding Induced by Cationic Drug Carriers in Articular Cartilage Using Donnan Osmotic Theory.

Background: Positively charged drug carriers are rapidly emerging as a viable solution for long-standing challenges in delivery to dense, avascular, negatively charged tissues. These cationic carriers have demonstrated especially strong promise in targeting drugs to articular cartilage for osteoarthritis (OA) treatment. It is critical to evaluate the dose-dependent effects of their high intratissue uptake levels on charge-shielding of anionic matrix constituents, and the resulting changes in tissue osmotic swelling and mechanical integrity.

Resveratrol and Curcumin Attenuate Sugar-Induced Cartilage Glycation, Stiffening, Senescence, and Degeneration.

Objective: Advanced glycation end-product (AGE) accumulation is implicated in osteoarthritis (OA) pathogenesis in aging and diabetic populations. Here, we develop a representative nonenzymatic glycation-induced OA cartilage explant culture model and investigate the effectiveness of resveratrol, curcumin, and eugenol in inhibiting AGEs and the structural and biological hallmarks of cartilage degeneration.

Design: Bovine cartilage explants were treated with AGE-bovine serum albumin, threose, and ribose to determine the optimal conditions that induce physiological levels of AGEs while maintaining chondrocyte viability.

Milk exosomes with enhanced mucus penetrability for oral delivery of siRNA.

Bovine milk-derived exosomes have recently emerged as a promising nano-vehicle for the encapsulation and delivery of macromolecular biotherapeutics. Here we engineer high purity bovine milk exosomes (mExo) with modular surface tunability for oral delivery of small interfering RNA (siRNA). We utilize a low-cost enrichment method combining casein chelation with differential ultracentrifugation followed by size exclusion chromatography, yielding mExo of high concentration and purity.