Mesoporous Silica Nanoparticles for Increasing the Oral Bioavailability and Permeation of Poorly Water Soluble Drugs

Abstract

We investigate the effects of spherical mesoporous silica nanoparticles (MSNs) as an oral drug delivery system to improve the oral bioavailability of the model drug telmisartan (TEL) and examine their cellular uptake and cytotoxicity. Further, we explore the mechanisms behind the improved oral absorption of poorly soluble drugs promoted by MSNs. An investigation of intestinal epithelial cellular binding, association and uptake was carried out by laser scanning confocal microscopy, transmission electron microscopy and fluorescence activated cell sorting. The results show that the cellular uptake is highly time-, concentration- and size-dependent. The model drug permeability studies in the human colon carcinoma (Caco-2) cell lines indicated that MSNs could significantly enhance TEL permeability and reduce rate of drug efflux. After loading TEL into MSNs, its oral bioavailability was compared with that of the marketed product Micardis and TEL-loaded ordered mesoporous silica microparticles (MSMs) in beagle dogs. The relative bioavailability of TEL-loaded MSN formulation and TEL-loaded MSM formulation was 154.4 ± 28.4% and 129.1 ± 15.6%, respectively. MSNs offer the potential to achieve enhanced oral bioavailability of poorly soluble drugs via improved drug dissolution rate and enhanced drug permeability.

Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles

“…There are a few studies demonstrating increased drug bioavailability and/or permeability for drug-loaded MSN formulations after oral administration [48][49][50][51] relying on the enhanced solubility that can be attained for poorly soluble drugs upon loading into a porous matrix with subsequent release into the GI tract. 52,53 To our knowledge, however, the present study is the first to demonstrate the potential of intestinal targeting of the MSN drug delivery carrier itself, with subsequent cellular uptake and intracellular release of a poorly soluble drug important for clinical use.…”

Targeted delivery of mesoporous silica nanoparticles loaded monastrol into cancer cells: an in vitro study

“…Mesoporous silica nanoparticles are considered to be very promising candidate for drug delivery specifically for water-insoluble drug. Due to large surface areas and pores, these MSNPs act as reservoirs for storing hydrophobic drugs, whereas their shape and size can be altered according to the requirements (Zhang et al 2012;Bharti et al 2015). Several drugs with low water solubility have been explored to demonstrate this concept including ibuprofen, rifampin, etc.…”

Silica-coated flexible liposomes as a nanohybrid delivery system for enhanced oral bioavailability of curcumin

“…26 A large number of silica-based pharmaceutical studies have been reported, including controlled and targeted drug delivery, even at the subcellular level. [27][28][29] In contrast to most of the other reports in this field, Dessivio et al 15 proposed a hybrid strategy to take advantage of both silica and organic systems. The constructed silica-coated liposomes, called "Liposil," possessed the high stability of silica materials and versatile drug-loading capabilities of liposomes, providing a novel potential carrier for drug delivery, especially in hostile bioenvironments.…”