Use of pH-sensitive microcapsules for selective delivery of nanozymes and biological enzymes in small intestine.

Unlike the intravenous route, oral delivery systems face challenges due to an acidic gastric environment, which can degrade or inactivate therapeutic compounds before they reach the small intestine (SI). Therefore, developing oral delivery strategies that protect cargo from acidic environments and release the content in the SI is imperative. Herein, a novel approach utilizes the pH-sensitivity of alginate-based microcapsules that degrade and release the contents at pH ≥ 7.0. The microcapsules were used to encapsulate gold nanoparticles (AuNPs, a model nanozyme) of varying sizes (2, 15, and 70 nm) and horseradish peroxidase (HRP, a model enzyme). The AuNPs- and HRP-loaded microcapsules (AuNPs-MCap and HRP-PEG MCap) were unaffected at acidic pH (2.0-6.0), as the intrinsic structure and properties of encapsulated AuNPs and HRP were intact. The microcapsules rapidly released the encapsulated AuNPs and HRP at pH ≥ 7.0. In vivo, oral administration of AuNPs-MCap and HRP-PEG MCap to Wistar rats also showed significantly enhanced absorption of AuNPs and HRP in SI, leading to higher concentrations in blood than in their corresponding unencapsulated forms. Overall, the results underscore the potential of pH-responsive microcapsules for protecting pH-sensitive nanozymes, biological enzymes and other bioactive compounds from the acidic gastric environment and for effective and targeted delivery to the SI.