Biocompatible Fe-Based Micropore Metal-Organic Frameworks as Sustained-Release Anticancer Drug Carriers

Abstract

Sustained-release preparation is a hot spot in antitumor drug research, where the first task is to select suitable drug carriers. Research has revealed that carboxylic acid iron metal–organic frameworks (MOFs), constructed from iron (Fe) ions and terephthalic acid, are nontoxic and biocompatible. Due to the breathing effect, the skeleton of this mesoporous material is flexible and can reversibly adapt its pore size through drug adsorption. Therefore, we chose one kind of Fe-MOF, MIL-53(Fe), as a carrier for the anticancer drug oridonin (Ori). In this work, we report the design and synthesis of MIL-53(Fe) and explore its ability as a transport vehicle to deliver Ori. MIL-53(Fe) is characterized by scanning electron microscopy and X-ray powder diffraction. A loading capacity of 56.25 wt % was measured by high performance liquid chromatography. This carrier was safe and nontoxic (cell viability > 95.27%), depending on the results of 3-(4,5-dimethylthiazol-2-yl)--2,5-diphenyltetrazolium bromide assays, lactate dehydrogenase assays, and Annexin V-fluoresce isothiocyanate/propidium iodide double-staining assays. After loading the drug, the structure of the MIL-53(Fe) was not destroyed, and Ori was amorphous in MIL-53(Fe). Based on an analysis of the Ori release profile, results suggest that it lasts for more than seven days in vitro. The cumulative release rate of Ori at the seventh day was about 82.23% and 91.75% in phosphate buffer saline solution at 37 °C under pH 7.2 and pH 5.5, respectively. HepG2 cells were chosen to study the cytotoxicity of Ori@MIL-53(Fe), and the results show that the anticancer ratio of Ori@MIL-53(Fe) system reaches 90.62%. Thus, MIL-53 can be used as a carrier for anticancer drugs and Ori@MIL-53(Fe) is a promising sustained-release drug delivery system for the cancer therapy.

Investigation of Metal-Organic Framework-5 (MOF-5) as an Antitumor Drug Oridonin Sustained Release Carrier

“…The drug loading of ORI@MOF-5 is as high as 52.86% ± 0.59%, which is much higher than other types of drug delivery systems, such as gold nanoparticles [46] or graphene oxides [47]. In our previous study [48], ORI was loaded by MIL-53 (Fe), and the drug loading was less than 50% under the same calculation method. Clinically, high drug loading can improve the efficiency of treatment and reduce the dosage of drug, which is of great significance.…”

A Novel Gel-Forming Solution Based on PEG-DSPE/Solutol HS 15 Mixed Micelles and Gellan Gum for Ophthalmic Delivery of Curcumin

“…To evaluate the release kinetics of Cur from the prepared formulations, a release study was carried out using a dialysis membrane with molecular weight cut-off of 8000 to 14,000 [36]. Each drug-loaded formulation (including 0.5 mg curcumin and STF (40:7, v/v)) was successively put into the dialysis bag and then immersed in the receiving vessels containing 60 mL of the release medium.…”

In Vitro Toxicity Study of a Porous Iron(III) Metal‒Organic Framework

“…We recently reported the in vitro hepatotoxicity of MIL-53(Fe), loaded the antitumor drug oridonin, and conducted in vitro sustained release and pharmacodynamic studies [43]. Although in vitro cell models are not a substitute for animal experiments, they can serve as a basis for further evaluation of the potential toxicity.…”