Oral drug delivery is widely used for treating gastric diseases as it allows drugs to act directly on gastric lesions, thereby improving therapeutic outcomes. However, its efficacy is hindered by the specific gastric environment, such as the gastric mucosal barrier, which limits drug penetration, and the short gastric emptying time, which results in transient residence time. Raw milk-derived extracellular vesicles (M-EVs) offer promise as a gastric drug delivery platform. Their high cellular affinity, stability under gastrointestinal conditions, and ability to protect drugs from acidic and enzymatic degradation make them suitable for this purpose. Incorporating mangetic nanoparticles encapsulated in M-EV provides magnetic navigation and active mucosal penetration capabilities. Herein, we developed a gastric drug delivery system based on iron-cobalt alloy@graphene (FeCo@G)-engineered M-EV (M-FNP). M-FNP serves as a versatile drug carrier that can load both small molecules and proteins through simple physical approach. And it demonstrates stability in the simulated gastric fluid system for at least 6 hours. Under magnetic field guidance, it penetrates the simulated mucosal layer and is internalized by cells within 4 hours significantly enhancing cellular drug uptake. M-FNP is expected to serve as an innovative drug delivery platform with enhanced retention capabilities within the stomach.
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