Functional properties and molecular docking of different nanoparticles with ROS-sensitive phenylboronylated chitosan as the carrier

Objective: To prepare chitosan-loaded nanoparticles (NPs) that enhance the oral bioavailability of puerarin (Pur) and render it responsive to reactive oxygen species (ROS). Significance: This research makes substantial progress towards the theory of intelligent drug delivery, offering a new reference for combining Pur with other natural medicinal active ingredients. Methods: The acylation reaction between chitosan and ROS-sensitive 3-carboxyphenylboronic acid (PBA) was used to synthesise ROS-sensitive phenylboronylated chitosan (PBACS). Subsequently, PBACS-PBA-Pur-NPs and PBACS-TPP-Pur-NPs were prepared via ion gelation after the addition of PBA and sodium tripolyphosphate(TPP), respectively. The physicochemical and functional properties of both NPs were compared, and their differences were preliminarily studied through molecular docking. Results: Reactive oxygen species-sensitive PBACS was successfully synthesised. Of the two NPs prepared, PBACS-TPP-Pur-NPs had a size of 127.2 +/- 0.80 nm, polydispersity index (PDI) of 0.129 +/- 0.0008, and an encapsulation rate of 95.75 +/- 0.387 %, whereas PBACS-PBA-Pur-NPs had a size of 149.8 +/- 0.1414 nm, PDI of 0.389 +/- 0.0012, and an encapsulation rate of 91.77 +/- 0.279 %. The micromorphology of the PBACS-TPP-Pur-NPs exhibited better physical properties. However, PBACS-PBA-Pur-NPs demonstrated a faster in vitro release and more significant in vitro anti-inflammatory effects. Pharmacokinetically, the AUC(0-24), T-max, and C-max of PBACS-PBA-Pur-NPs were 3.485, 2.117, and 3.339 times higher, respectively, than those of Pur. The AUC(0-24), T-max, and C-max of PBACS-TPP-Pur-NPs were 2.41, 1.33, and 2.03 times higher, respectively, than those of Pur. Molecular simulation revealed that the binding energy of PBACS-PBA-Pur -NPs was approximately -4.34 kcal/mol and that of PBACS-TPP-Pur-NPs was even lower, approximately -5.93 kcal/mol, suggesting that the NPs prepared with TPP are more densely packed than those designed with PBA, resulting in slower and reduced drug release. Conclusion: The NPs constructed in this study effectively reduced inflammatory factors at the disease site, providing a theoretical and experimental basis for the application of nano drugs in inflammatory disease models. In addition, the molecular docking study of the two NPs offered insights into the relationship between the release and structure of subsequent nano drugs.