Facile synthesis of PEI-based crystalline templated mesoporous silica with molecular chirality for improved oral delivery of the poorly water-soluble drug

Abstract

The aim of this study was to build up a novel chiral mesoporous silica called PEIs@TA-CMS through a facile biomimetic strategy and to explore its potential to serve as a drug carrier for improving the delivery efficiency of poorly water-soluble drug. PEIs@TA-CMS was synthesized by using a chiral crystalline complex associated of tartaric acid and polyethyleneimine (PEIs) as templates, scaffolds and catalysts. The structural features including morphology, size, pore structure and texture properties were systematacially studied. The results showed that PEIs@TA-CMS was monodispersed spherical nanoparticles in a uniformed diameter of 120–130 nm with well-developed pore structure (S BET : 1009.94 m 2 /g, pore size <2.21 nm). Then PEIs@TA-CMS was employed as nimodipine (NMP) carrier and compared with the drug carry ability of MCM41. After drug loading, NMP was effectively transformed from the crystalline state to an amorphous state due to the space confinement in mesopores. As expected, PEIs@TA-CMS had superiority in both drug loading and drug release compared to MCM41. It could incorporate NMP with high efficiency, and the dissolution-promoting effect of PEIs@TA-CMS was more obvious because of the unique interconnected curved pore channels. Meanwhile, PEIs@TA-CMS could significantly improve the oral adsorption of NMP to a satisfactory level, which showed approximately 3.26-fold higher in bioavailability, and could effectively prolong the survival time of mice on cerebral anoxia from 10.98 to 17.33 min.

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

“…l / d / dl -TA-PEI@CMSN were synthesized according to a previously reported method by our group . First, the chiral biomimetic template l / d / dl -TA-PEI was prepared by grafting l / d / dl -TA onto the long chains of PEI via acid–base neutralization reactions.…”

“…L/D/DL-TA-PEI@CMSN were synthesized according to a previously reported method by our group. 35 First, the chiral biomimetic template L/D/DL-TA-PEI was prepared by grafting L/D/DL-TA onto the long chains of PEI via acid− base neutralization reactions. In brief, 0.316 g PEI and 0.3 g L/D/DL-TA were dispersed in 1 mL deionized water with stirring and placed in an ice−water bath to induce crystallization.…”

“…To be specific, (1) the twist chiral nanopores in CMSNs can hold abundant drug molecules and help to maintain the spatial conformational stability of some biomacromolecules, (2) the highly interconnected chiral pore networks of CMSNs are tunable and beneficial for hosting and releasing various types of therapeutic agents, (3) CMSNs with molecular chirality show potential chiral recognition functions and are susceptive to the chiral microenvironment in vivo , and (4) CMSNs with chiral surface topology always produce high friction when in contact with biosurfaces and have been proven to deliver the cargo more efficiently than their achiral counterparts . Although nanoscale rough surfaces have been revealed to minimize the repulsive forces between NPs and biosurfaces, the exact stereoselective tendency still remains unclear. − …”