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Overcoming oral delivery barriers of functional proteins: current status and advanced delivery technologies
Zhang Jianghao1, Salumu Masuwa Shadrack1, Wang Mingcheng2
1School of Life Science, Shaoxing University, Shaoxing, Zhejiang, China; Department of Food Quality and Safety, National R&D Center for Chinese Herbal Medicine Processing, College of Engineering, China Pharmaceutical University, Nanjing, Jiangsu, China.
Abstract:
Proteins and peptides from functional foods offer notable health benefits, yet their efficacy is hindered by low solubility, enzymatic degradation, poor absorption, metabolic limitations, and gastrointestinal instability. This review summarizes the major barriers affecting oral delivery and evaluates their impact on functional performance. It provides an overview of key delivery strategies-including lipid-based carriers, polymeric systems, mucoadhesive technologies, and physicochemical methods-designed to enhance stability and bioavailability. The potential of smart delivery systems responsive to physiological signals for targeted or controlled release is also highlighted. Advantages and limitations of these approaches are compared to offer a balanced understanding of their applicability. In addition, the review discusses the emerging use of artificial intelligence and machine learning to optimize carrier design, predict formulation behavior, and accelerate development. By integrating technological advances with performance assessment, it identifies knowledge gaps, examines promising alternatives, and outlines future directions for next-generation delivery systems for functional proteins and peptides.
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