Enhanced Transport of Shape and Rigidity-Tuned α-Lactalbumin Nanotubes across Intestinal Mucus and Cellular Barriers
| Autor: | Jingjing Chai, Lulu Jiao, Zhengquan Yu, Fazheng Ren, Cheng Bao, Bin Li, Liwei Zhang, Xinghua Shi, Bin Liu, Yuan Li, Dan Li |
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| Rok vydání: | 2020 |
| Předmět: |
Curcumin
Biological Availability Nanoparticle Bioengineering 02 engineering and technology Permeability Mice Animals Humans General Materials Science Lactalbumin Drug Carriers Nanotubes Intestinal mucus Chemistry Mechanical Engineering Dextran Sulfate General Chemistry Penetration (firestop) 021001 nanoscience & nanotechnology Condensed Matter Physics Mucus Intestines Biophysics Nanoparticles Colitis Ulcerative Caco-2 Cells 0210 nano-technology Nanospheres Oral retinoid |
| Zdroj: | Nano Letters. 20:1352-1361 |
| ISSN: | 1530-6992 1530-6984 |
| DOI: | 10.1021/acs.nanolett.9b04841 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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