Mesoporous silica nanorods for improved oral drug absorption

Abstract

Mesoporous silica nanoparticles (MSNs) have been widely used in biomedical applications. However, most studies have been limited to spherical MSNs, while non-spherical MSNs have never been rigorously studied. In this study, we fabricated mesoporous silica nanospheres (MSNSs) and mesoporous silica nanorods (MSNRs), with different aspect ratios (ARs) but identical surface chemistries to explore the shape effects of MSNs on oral delivery. The results of cellular studies demonstrated that MSNRs exhibited a higher cellular uptake than MSNSs. Mechanistic studies showed that caveolae-mediated endocytosis was involved in the uptake of MSNRs, while the clathrin-dependent pathway contributed to the endocytosis of MSNSs. Meanwhile, the apparent permeability coefficient value (P) of doxorubicin hydrochloride (Dox)-loaded MSNRs was approximately 1.8-, 3.2- and 6.3-fold higher than that of Dox-loaded MSNS1, Dox-loaded MSNS2 and Dox solution, respectively. The in vivo pharmacokinetics study showed that the area under the plasma concentration-time curve (AUC) achieved by Dox-loaded MSNRs was 1.9-, 3.4- and 5.7-fold higher than the corresponding values for Dox-loaded MSNS1, MSNS2 and Dox solution, respectively. Taken together, our results demonstrated that tuning nanoparticle shape potentially determines the biological fate of nanoparticles with higher delivery efficiency, such as enhanced cellular uptake and oral bioavailability.

Effect of Shape on Mesoporous Silica Nanoparticles for Oral Delivery of Indomethacin

“…Yu et al noted that, compared to mesoporous silica nanospheres, rod-like particles are not easily trapped by mesh structure of mucus and diffuse faster because MSNRs can rotate and jump in mucus [24]. In a previous study, we also found that the cellular uptake efficiency and internalization mechanism were both dependent on the shape, in which the caveolae-dependent pathway was involved in the uptake of MSNRs and that clathrin-dependent endocytosis contributed to the behavior of MSNSs, respectively [30]. In general, the caveolae-dependent pathway can translocate part of nanoparticles to endoplasmic reticulum or Golgi, leading to a higher uptake efficiency, while MSNSs pass through the clathrin-dependent pathway, and most particles are transferred into endosome and recycled outside the cell [47,48].…”

“…The mesoporous silica nanospheres (MSNSs) were prepared by using a previously reported method [30]. Briefly, 0.28 g NaOH and 1 g CTAB were dissolved in 480 mL deionized water in an 80 °C water bath.…”

“…Different concentrations of MSNs (0.01, 0.02, 0.05, 0.1, 0.2, 0.5, and 1 mg/mL) were prepared and added to the cells for 24 h; subsequently, 20 μL MTT solution (5 mg/mL) was added into each well, and the plates were incubated for a further 4 h. The medium was then removed and DMSO (150 μL) was added to dissolve the MTT formazan crystals. Finally, the absorbance of the formazan product at 490 nm was measured by using a ThermoFisher Microplate Reader [30].…”

<p>Superiority of L-tartaric Acid Modified Chiral Mesoporous Silica Nanoparticle as a Drug Carrier: Structure, Wettability, Degradation, Bio-Adhesion and Biocompatibility</p>

“…1,3,9 A substantial number of studies have reported the applications of MSNs as drug carriers, and the use of MSNs as drug carriers have been proven to be successful in vitro. [6][7][8][10][11][12] To the best of our knowledge, the efficacy of MSN carriers is decided by the structural features which determine the physicochemical properties of MSNs, including shape, size, pore characteristics, and surface chemistry. 13 Along with great progress in the structure control and multi-functionalization design of MSNs, various drug delivery formulations such as immediate drug delivery systems, sustained drug delivery systems, controlled drug delivery systems, targeted drug delivery systems, and stimuli-responsive drug delivery systems have been developed to improve the dissolution and bioavailability of poorly water-soluble drugs and enhance their therapeutic potential.…”

“…13 Along with great progress in the structure control and multi-functionalization design of MSNs, various drug delivery formulations such as immediate drug delivery systems, sustained drug delivery systems, controlled drug delivery systems, targeted drug delivery systems, and stimuli-responsive drug delivery systems have been developed to improve the dissolution and bioavailability of poorly water-soluble drugs and enhance their therapeutic potential. [9][10][11][12]14,15 It should be noted that, a slight change in structural features of MSNs may not only significantly influence their host-guest interactions with drug molecules, but also impact the biological binding ability with tissues and cells. 4,16 For example, Lu et al demonstrated that decreasing the size of NPs (from 50-280 nm) is an effective way to facilitate the cell uptake of MSNs.…”