Mucus is a viscoelastic biological hydrogel that protects the epithelial surface from penetration by most nanoparticles, which limits the efficiency of oral drug delivery. Pursuing highly efficient, biocompatible, and biodegradable oral drug vehicles is of central importance to the development of promising nanomedicine. Here, we prepared five peptosomes (PSs) with various sizes, shapes, and rigidities based on self-assembly of amphiphilic α-lactalbumin (α-lac) peptides from partial enzymolysis and cross-linking. The mucus permeation of α-lac PSs and release of curcumin (Cur) encapsulated in these PSs were evaluated. Compared with a long nanotube, big nanosphere, small nanosphere, and cross-linked short nanotube, we demonstrated that a short nanotube (SNT) exhibits excellent permeability in mucus, which enables it to arrive at epithelial cells quickly. Besides, SNT exhibits the highest cellular uptake and transmembrane permeability on Caco-2/HT29-MTX (E12) 3D coculture model. In vivo pharmacokinetic evaluation revealed that SNT formulation shows the highest curcumin bioavailability, which is 6.85-folds higher than free Cur. Most importantly, Cur loaded in SNT exhibits the optimum therapeutic efficacy for in vivo treatment of dextran sulfate sodium (DSS)-induced ulcerative colitis. In the end, the mechanism of the high permeability of SNTs through mucus was explained by coarse-grained molecular dynamics simulations, which indicated that short time scale jiggling and flying across pores of mucus network played key roles. These findings revealed the tubular α-lac PSs could be a promising oral drug delivery system targeted to mucosal for improving absorption and bioavailability of hydrophobic bioactive ingredients.

The codelivery system for multiple antioxidants such as anthocyanins (Ant) and curcumin (Cur) of synergistic action may effectively enhance their stability and cellular absorption. We have reported that amphiphilic peptides obtained from enzymatic partial hydrolysis of α-lactalbumin (α-lac) can self-assemble into 20 nm monodispersed nanomicelles in aqueous solution. Cur and Ant could be coloaded into the micelles sequentially via hydrophobic and electrostatic interactions, which was proved by fluorescence quenching experiments for the Cur–micelle and Ant–micelle interactions. Circular dichroism spectra proved that the Cur and Ant binding did not affect their structure confirmation. Both Cur- and Ant-loaded micelles showed improved stability and also exhibited an intestinal pH responsive release property in simulated gastrointestinal fluid. In addition, the nanomicelles exhibited an advanced cellular uptake and transmembrane permeability based on Caco-2 cell monolayer models. Finally, the coloaded micelles possessed a synergistic efficiency such that cellular antioxidant activity (CAA) for Cur and Ant was markedly improved.

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Background:Rhinitis is the most common clinical manifestation of allergy, affecting more than 400 million people around the world. Rhinitis increases the risk of developing bronchial hyper-responsiveness and asthma. Previous studies have shown that rhinitis is closely related with the physiology, pathology, and pathogenesis of asthma. We analyzed co-expressed genes to explore the relationships between rhinitis and asthma and to find biomarkers of comorbid rhinitis and asthma. Material/Methods:Asthma-and rhinitis-related differentially-expressed genes (DEGs) were identified by bioinformatic analysis of GSE104468 and GSE46171 datasets from the Gene Expression Omnibus (GEO) database. After assessment of Gene Ontology (GO) terms and pathway enrichment for DEGs, a protein-protein interaction (PPI) network was conducted via comprehensive target prediction and network analyses. We also evaluated co-expressed DEGs and corresponding predicted miRNAs involved in the developing process of rhinitis and asthma. Results:We identified 687 and 1001 DEGs in bronchial and nasal epithelia samples of asthma patients, respectively. For patients with rhinitis, we found 245 DEGs. The hub-genes of PAX6, NMU, NTS, NMUR1, PMCH, and KRT6A may be associated with rhinitis, while CPA3, CTSG, POSTN, CLCA1, HDC, and MUC5B may be involved in asthma.The co-expressed DEGs of BPIFA1, CCL26, CPA3, and CST1, together with corresponding predicted miRNAs (e.g., miR-195-5p and miR-125a-3p) were found to be significantly correlated with rhinitis and asthma. Conclusions:Rhinitis and asthma are related, and there are significant correlations of BPIFA1, CCL26, CPA3, and CST1 genes with novel biomarkers involved in the comorbidity of rhinitis and asthma.

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