OICC Press Journal of Nanostructure in Chemistry 2193-8865 14 4 2022 09 20 Chitosan conjugated-ordered mesoporous silica: a biocompatible dissolution enhancer for promoting the antidiabetic effect of a poorly water-soluble drug of repaglinide 10.1007/s40097-022-00515-z EN Aziz Maleki Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Zanjan University of Medical Sciences, Zanjan, 45139-56184, IR Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, 45139-56184, IR Shayesteh Bochani Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, 45139-56184, IR Mehraneh Kermanian Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Zanjan University of Medical Sciences, Zanjan, 45139-56184, IR Pooyan Makvandi Centre for Materials Interfaces, Istituto Italiano Di Tecnologia, Pisa, 56025, IT Mir-Jamal Hosseini Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, 45139-56184, IR Mehrdad Hamidi Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Zanjan University of Medical Sciences, Zanjan, 45139-56184, IR Trita Nanomedicine Research and Technology Development Center (TNRTC), Zanjan, 45156-13191, IR Ali Kalantari-Hesari Department of Pathobiology, Faculty of Veterinary Science, Bu-Ali Sina University, Hamadan, IR Hamid Reza Kheiri Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Zanjan University of Medical Sciences, Zanjan, 45139-56184, IR Department of Biotechnology, Faculty of Pharmacy, Zanjan University of Medical Sciences, Zanjan, 45139-56184, IR Mohammad Reza Eskandari Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, IR Maryam Rosta Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, IR Virgilio Mattoli Centre for Materials Interfaces, Istituto Italiano Di Tecnologia, Pisa, 56025, IT Seyed Hojjat Hosseini Department of Physiology and Pharmacology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, IR Journal Article 2022 09 20 Abstract The oral pathway is the preferred drug administration route in pharmaceutical sciences, however, the most employed ‘highly active’ drug candidates suffer from poor water solubility. The aim of this study was to develop repaglinide (RL)-loaded chitosan-grafted mesoporous silica material (MSM) to enhance drug dissolution. Such enhanced dissolution was investigated in in vitro and in vivo conditions. Our results showed successful grafting of chitosan (CN) on the surface of the MSM and the loading of RL into the mesopores of the silica host. Furthermore, the obtained drug dissolution profiles were fitted to mathematical models to characterize and compare drug dissolution profiles. Cytotoxicity evaluation against the human colorectal adenocarcinoma (Caco-2) cell line showed concentration-dependent toxicity for the MSN-based particles. Various liver and kidney mitochondrial functional parameters including lipid peroxidation assay, complex II activity, mitochondrial glutathione (GSH) level assay, ferric reducing antioxidant power (FRAP) assay, protein carbonyl level, and reactive oxygen species (ROS) formation, were used to investigate the biosafety of the silica-based dissolution enhancer. A significant reduction in blood glucose was observed after oral administration of the biocomposites for 24 h. The histopathological studies of the kidney and liver indicated no MSM-related adverse effects. We believed that our achievements can help the use of the hybrid organic–inorganic MSMs in improving the bioavailability of PWSDs in the one hand and, on the other hand, open a novel avenue to develop biocompatible and nontoxic MSMs in oral bioavailability of PWSDs. Graphical abstract