A Eu³⁺/Gd³⁺-EDTA-doped structurally controllable hollow mesoporous carbon for improving the oral bioavailability of insoluble drugs andin vivotracing

Abstract

A structurally controllable fluorescence-labeled hollow mesoporous carbon (HMC) was simply prepared to improve the oral bioavailability of insoluble drugs and further trace their delivery process in vivo. The hollow structure was derived from an inverse replica process using mesoporous silica as a template and the fluorescent label was prepared by doping the carboxylated HMC with a confinement of Eu(3+)/Gd(3+)-EDTA. The physicochemical properties of the composites were systematically characterized by transmission electron microscopy, Fourier transform infrared spectroscopy and photoluminescence spectra tests prior to studying their effects on drug-release behavior and biodistribution. As a result, the thickness of the carrier's shell was adjusted from 70 nm to 130 nm and the maximum drug loading was up to 73.6%. The model drug carvedilol (CAR) showed sustained release behavior compared to CAR commercial capsules, and the dissolution rate slowed down as the shells got thicker. AUC0-48h and Tmax were enlarged 2.2 and 6.5 fold, respectively, which demonstrated that oral bioavailability was successfully improved. Bioimaging tests showed that the novel carbon vehicle had a long residence time in the gastrointestinal tract. In short, the newly designed HMC is a promising drug carrier for both oral bioavailability improvement and in vivo tracing.

Biodistribution of Mesoporous Carbon Nanoparticles via Technetium-99m Radiolabelling after Oral Administration to Mice

“…Throughout the duration of the biodistribution study, practically no uptake was observed in the other major organs, thus we expect any possible side effects from drug administration via loading of the developed MCNs to be minimal. Similar results were shown by other groups investigating the in vivo kinetics of drug nanocarriers with radiolabelling or fluorescent-labelling techniques [47,77]. As mentioned previously, in the presence of SGF radiolabelling, integrity is affected and 99m Tc is released from the nanostructure, but not distributed in vivo (no radioactivity has been detected in other organs or tissues).…”

Drug Delivery With Carbon-Based Nanomaterials as Versatile Nanocarriers: Progress and Prospects

“…Surface modifications are also feasible with ligand or polymer to obtain tumor-targeted or stimulus-responsive drug delivery. Controllable hollow mesoporous carbon labeled with fluorescence (Eu 3+ /Gd 3+ -EDTA) was developed to improve the oral bioavailability of insoluble drugs (carvedilol) (Liu et al, 2016). Eu 3+ /Gd 3+ -EDTA significantly improved the oral bioavailability and showed longer residency in the gastrointestinal tract which was confirmed by the bio-image test.…”

Mesoporous carbon nanomaterials in drug delivery and biomedical application

“…Liu et al. ( 2016a ) reported using an Eu 3+ /Gd 3+ -EDTA-doped hollow mesoporous carbon (HMC) to improve the oral bioavailability of an insoluble model drug carvedilol (CAR) and to achieve in vivo imaging. The drug-loading efficiency (LE%) of the carboxylated HMC (SHMC) could reach up to 73.6% by the solvent evaporation method and 47.8% by the adsorption equilibrium method.…”

“…To control the drug release, HMCNs with different shell thickness from 70 nm to 130 nm were prepared by Liu et al. ( 2016b ). And higher drug-loading capacity is another appealing characteristic of HMCNs due to the unique hollow core structure and accessible pore channels on the mesoporous shell which could act as a depot of the drugs.…”