Chiral nanoparticles (NPs) with nanoscale rough surfaces
have enormous
application prospects in drug delivery. However, the stereoselective
interactions between the chiral NPs and biosurfaces remain challenging
and mysterious. Herein, we designed mesoporous silica nanocarriers
(l/d/dl-TA-PEI@CMSN) exhibiting the same
structural parameters (hydrophilic, electroneutral, spherical NPs,
∼120 nm) but different geometrical chirality as oral nanodrug
delivery systems (Nano-DDS) for insoluble drugs nimesulide (NMS) and
ibuprofen (IBU) and demonstrated their stereoselective interactions
with the intestinal mucosa, that is, l-TA-PEI@CMSN as well
as Nano-DDS in the l-configuration displayed apparent superior
behaviors in multiple microprocesses associated with oral adsorption,
including adhesion, penetration, adsorption, retention and uptake,
causing by the stereomatching between the chiral mesostructures of
NPs and the inherent chiral topologies of the biosurfaces. As hosting
systems, l/d/dl-TA-PEI@CMSN effectively
incorporated drugs in amorphous states and helped to overcome the
stability, solubility and permeability bottlenecks of drugs. Subsequently,
Nano-DDS in the l-configuration (including IBU/l-TA-PEI@CMSN and NMS/d-TA-PEI@CMSN owing to a chiral inversion)
showed higher oral delivery efficiency of NMS and IBU evidenced by
the larger relative bioavailability (1055.06% and 583.17%, respectively)
and stronger anti-inflammatory and analgesic effects. In addition, l/d/dl-TA-PEI@CMSN were stable, nonirritative,
biocompatible and biodegradable, benefiting for their clinical applications.
These findings provided insights into the rational design of functionalized
Nano-DDS and contributed to the further knowledge in the field of
chiral pharmaceutical science.