Chiral mesoporous silica nano-screws as an efficient biomimetic oral drug delivery platform through multiple topological mechanisms.
Acta Pharm Sin B
; 12(3): 1432-1446, 2022 Mar.
Article
en En
| MEDLINE
| ID: mdl-35530160
ABSTRACT
In the microscale, bacteria with helical body shapes have been reported to yield advantages in many bio-processes. In the human society, there are also wisdoms in knowing how to recognize and make use of helical shapes with multi-functionality. Herein, we designed atypical chiral mesoporous silica nano-screws (CMSWs) with ideal topological structures (e.g., small section area, relative rough surface, screw-like body with three-dimension chirality) and demonstrated that CMSWs displayed enhanced bio-adhesion, mucus-penetration and cellular uptake (contributed by the macropinocytosis and caveolae-mediated endocytosis pathways) abilities compared to the chiral mesoporous silica nanospheres (CMSSs) and chiral mesoporous silica nanorods (CMSRs), achieving extended retention duration in the gastrointestinal (GI) tract and superior adsorption in the blood circulation (up to 2.61- and 5.65-times in AUC). After doxorubicin (DOX) loading into CMSs, DOX@CMSWs exhibited controlled drug release manners with pH responsiveness in vitro. Orally administered DOX@CMSWs could efficiently overcome the intestinal epithelium barrier (IEB), and resulted in satisfactory oral bioavailability of DOX (up to 348%). CMSWs were also proved to exhibit good biocompatibility and unique biodegradability. These findings displayed superior ability of CMSWs in crossing IEB through multiple topological mechanisms and would provide useful information on the rational design of nano-drug delivery systems.
APTES, 3-aminopropyltriethoxysilane; AR, aspect ratio; AUC0â∞, area under the curve; CMSRs, chiral mesoporous silica nanorods; CMSSs, chiral mesoporous silica nanospheres; CMSWs, chiral mesoporous silica nano-screws; CMSs, chiral mesoporous silicas nanoparticles; Cd, drug loading capacity; Chiral mesoporous silica; Cmax, maximum concentration; DAPI, 4,6-diamidino-2-phenylindole; DCM, dichloromethane; DOX, doxorubicin; EDC·HCl, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; FBS, fetal bovine serum; FITC, Fluorescein isothiocyanate; Frel, relative bioavailability; GI, gastrointestinal; Geometric topological structure; HOBT, 1-hydroxybenzotriazole; IEB, intestinal epithelium barrier; IR, infrared spectroscopy; Intestinal epithelium barrier; MRT0â∞, mean residence time; MSNs, mesoporous silica nanoparticles; Morphology; Mß-CD, methyl-ß-cyclodextrin; N-PLA, N-palmitoyl-l-alanine; NPs, nanoparticles; Nano-screw; Oral adsorption; PBS, phosphate buffer solution; RBCs, red blood cells; RITC, rhodamine B isothiocyanate; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SBET, Specific surface area; SBF, simulated body fluid; SD, SpragueDawley; SGF, simulated gastric fluid; SIF, simulated intestinal fluid; TEOS, ethylsilicate; Tmax, peak time; Vt, pore volume; WBJH, pore diameter; XRD, X-ray diffractometry; nano-DDS, nano-drug delivery systems; t1/2, half-life
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Acta Pharm Sin B
Año:
2022
Tipo del documento:
Article
País de afiliación:
China