Microencapsulation and characterization of controlled-release intestinal drugs: a critical review

Oral administration is associated with high patient adherence, as it is not only the route for primary site absorption of nutrients and peptide drugs but also is important for treating intestinal diseases. However, traditional oral intestinal drugs are limited by drug degradation and inactivation, particularly for proteins and peptides, due to gastric acid and digestive enzymes, making it difficult to effectively deliver drugs to target sites. To address these challenges, controlled-release microencapsulated intestinal drugs (MeIDs) have been developed and have attracted attention for their ability to protect drugs from degradation by gastric acid and digestive enzymes. In this study, we systematically reviewed research articles on the preparation methods, release mechanisms, and evaluation strategies of MeIDs using Google Scholar, Web of Science, and Science Direct databases. Our findings show that the preparation of emulsions, microencapsulation methods, shell material selection, and drug properties need to be considered comprehensively for MeID development. In addition, we found that coating, micro/nanocarriers, and absorption enhancers can be combined to enhance microcapsule performance. Beyond focusing on drug loading efficiency and microcapsule morphology, we also found that cell models, animal models, and spectroscopic analysis techniques can be used to evaluate drug biocompatibility, stability, and efficacy. Finally, the literature has shown that optimizing the preparation process can regulate drug release kinetics. For future research, we suggest that studies should focus on low-cost methods for producing monodisperse microcapsules, developing dynamic responsive shell materials, and using organ-on-a-chip technology for precise evaluation, as part of the theoretical support towards the development of microencapsulated drugs and targeted drug delivery.