Chiral Nanosilica Drug Delivery Systems Stereoselectively Interacted with the Intestinal Mucosa to Improve the Oral Adsorption of Insoluble Drugs

• Published in: ACS nano Vol. 17; no. 4; pp. 3705 - 3722
• Main Authors: Chen, Xuchun, Cheng, Ying, Pan, Qi, Wu, Lan, Hao, Xinyao, Bao, Zhiye, Li, Xitan, Yang, Mingshi, Luo, Qiuhua, Li, Heran
• Format: Journal Article
• Language: English
• Published: United States 28.02.2023
• Subjects: Adsorption; Anti-Inflammatory Agents - chemistry; Drug Carriers - chemistry; Drug Delivery Systems; Ibuprofen - chemistry; Intestinal Mucosa; Nanoparticles - chemistry; Silicon Dioxide - chemistry; stereoselective interaction; intestinal mucosa; chiral mesoporous silica; oral adsorption; chiral nanosilica drug delivery systems
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.2c10818

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.