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 m²/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.

Keywords: Biomimetic synthesis; chiral mesoporous silica; drug delivery; nimodipine; oral bioavailability.

Figure 1.

(A) FTIR spectra of (a) PEIs, (b) L-tartaric, (c) PEIs@TA, and the representation of the formation of PEIs@TA (in the embedded response equation); (B) FTIR spectra of (a) PEIs@TA, (b) PEIs@TA-CMS before calcine, and (c) PEIs@TA-CMS after calcine; (C) FTIR spectra of (a) NMP, (b) the physical mixture of NMP and PEIs@TA-CMS, (c) NMP/PEIs@TA-CMS, and (d) PEIs@TA-CMS; (D) FTIR spectra of (a) NMP, (b) the physical mixture of NMP and MCM41, (c) NMP/MCM41, and (d) MCM41.

Figure 2.

Structural characteristics of PEIs@TA-CMS. (A) and (B) TEM images of PEIs@TA-CMS; (C) and (D) SEM images of PEIs@TA-CMS; (E) particle size distribution of PEIs@TA-CMS calculated from the SEM images; (F) particle size distribution of PEIs@TA-CMS obtained from the Zeta-Potential/Particle Sizer.

Figure 3.

(A) N₂ adsorption/desorption isotherm of PEIs@TA-CMS and NMP/PEIs@TA-CMS; (B) N₂ adsorption/desorption isotherm of MCM41 and NMP/MCM41; (C) pore size distribution of PEIs@TA-CMS and NMP/PEIs@TA-CMS; (D) pore size distribution of MCM41 and NMP/MCM41.

Figure 4.

Structural characteristics of MCM41. (A) and (B) TEM images of MCM41; (C) and (D) SEM images of MCM41; (E) particle size distribution of MCM41 calculated from the SEM images; (F) particle size distribution of MCM41 obtained from the Zeta-Potential/Particle Sizer.

Figure 5.

(A) XRD diffractograms of (a) NMP, (b) the physical mixture of NMP and PEIs@TA-CMS, (c) NMP/PEIs@TA-CMS, and (d) PEIs@TA-CMS; (B) XRD diffractograms of (a) NMP, (b) the physical mixture of NMP and MCM41, (c) NMP/MCM41, and (d) MCM41; (C) DSC thermograms of (a) NMP, (b) the physical mixture of NMP and PEIs@TA-CMS, (c) NMP/PEIs@TA-CMS, and (d) PEIs@TA-CMS; (D) DSC thermograms of (a) NMP, (b) the physical mixture of NMP and MCM41, (c) NMP/MCM41, and (d) MCM41.

Figure 6.

(A) In vitro drug release profiles of NMP, NMP/PEIs@TA-CMS and NMP/MCM41; (B) in vitro drug release profiles of NMP/PEIs@TA-CMS (1:1), NMP/PEIs@TA-CMS (1:2) and NMP/PEIs@TA-CMS; (C) plasma concentration–time profiles of NMP, NMP/PEIs@TA-CMS and NMP/MCM41; (D) the survival time of mice on cerebral anoxia induced by NaNO₂. *p < 0.05, ***p < 0.001.