Virus-Mimicking Mesoporous Silica Nanoparticles with an Electrically Neutral and Hydrophilic Surface to Improve the Oral Absorption of Insulin by Breaking Through Dual Barriers of the Mucus Layer and the Intestinal Epithelium.

Protein and peptide drugs orally suffer from extremely low bioavailability principally for the complicated gastrointestinal environment along with the difficulty of passing through the mucus layer and the underlying epithelium. In our work, we fabricated mesoporous silica nanoparticles with modification groups (MSN-NH2@COOH/CPP5) that effectively penetrated the mucus layer and passed through the intestinal epithelium by mimicking the virus surface. Naked nanoparticles were prepared with inner pores of 6 nm diameter to allow efficient insulin loading and coated with the cationic cell-penetrating KLPVM peptide and the anionic glutaric anhydride to yield hydrophilic MSN-NH2@COOH/CPP5 with a ζ-potential of -0.49 mV. The apparent permeability coefficient of virus-mimicking nanoparticles was 14.61 × 10-5 cm/s. The virus-mimicking nanoparticles showed dramatically lower binding to mucin and faster penetration of the mucus layer than positively charged nanoparticles (MSN@NH2) with a ζ-potential of +35.00 mV. The KLPVM peptide enhanced the uptake of MSN-NH2@COOH/CPP5 by coculturing Caco-2 and E12 cells as an intestinal epithelium model. MSN-NH2@COOH/CPP5 enhanced apical-to-basal transcytosis for being internalized primarily through caveolae-mediated endocytosis. Indeed, for MSN-NH2@COOH/CPP5, the transepithelial transport of the Caco-2 cell monolayer was 2.4-fold higher than MSN@NH2 and 2.0-fold higher than MSN-NH2@COOH. In vitro, loading insulin into nanoparticles maintained the bioactivity of the protein under simulated intestinal conditions. Insulin loaded into MSN-NH2@COOH/CPP5 reduced the diabetic rats' blood glucose level by nearly 50%. The bioavailability of insulin encapsulated in the MSN-NH2@COOH/CPP5 nanoparticles was 2.1-fold more than insulin when administered directly into the jejunum. Nanoparticles with modifications indicated no significant toxicity in in vitro or in vivo preliminary studies. The obstacles of the mucus layer and intestinal epithelium may be effectively conquered by these virus-mimicking nanoparticles for oral delivery of protein and peptide drugs.

Occurrence of phosphorus, iron, aluminum, silica, and calcium in a eutrophic lake during algae bloom sedimentation.

Phosphorus (P) in a water body is mainly controlled by the interaction between surface sediment and the overlying water column after the complete control of external pollution. Significant enhancement of P in a water body would cause eutrophication of lakes. Thus, a better understanding is needed of the occurrences of P between the sediment and water column in eutrophic lakes. Here, we measured total phosphorus (TP) and major elements (Fe, Al, Ca, Mn, Si) in the water column, and total nitrogen, organic matter, TP and major oxides (Fe2O3, Al2O3, CaO, SiO2) in surface sediment of Chaohu Lake, a continuously eutrophic lake. The results showed that the rank of TP levels was western lake > eastern lake > southern lake. There were significantly positive correlations between TP (including water TP and sedimentary TP) and Fe, Al, Mn, while the correlation coefficients between water TP and sedimentary TP were -0.43, -0.41 and 0.18 for the western, eastern and southern lake respectively. The negative and significant correlations of water TP and sedimentary TP may indicate that the risk of sedimentary P release was great in the western and eastern lake during algae bloom sedimentation, while the southern lake showed weak P exchange between the sediment and water column.