ZIF-8 as a promising drug delivery system for benznidazole: development, characterization, in vitro dialysis release and cytotoxicity

Abstract

Chagas disease (CD), caused by the flagellate protozoan Trypanosoma cruzi, is one of the major public health problems in developing countries. Benznidazole (BNZ) is the only drug available for CD treatment in most countries, however, it presents high toxicity and low bioavailability. To address these problems this study used Zeolitic Imidazolate Framework-8 (ZIF-8), which has garnered considerable attention due to its potential applications, enabling the controlled delivery of drugs. The present work developed and characterized a BNZ@ZIF-8 system, and the modulation of BNZ release from the ZIF-8 framework was evaluated through the in vitro dialysis release method under sink conditions at different pH values. Moreover, the in vitro evaluation of cell viability and cytotoxicity by MTT assay were also performed. The dissolution studies corroborated that a pH sensitive Drug Delivery System capable of vectorizing the release of BNZ was developed, may leading to the improvement in the bioavailability of BNZ. The MTT assay showed that no statistically significant toxic effects occurred in the developed system, nor significant effects on cell viability.

Effects of ZIF-8 MOFs on structure and function of blood components

“…Although the lung is not a hemopoietic organ, it is also involved in the formation of platelets. 18 Last, the kidney generates erythropoietin (EPO) which acts on the bone marrow hematopoietic system to promote the differentiation and maturation of pronormoblasts, facilitate the uptake and utilization of Fe in bone marrow, accelerate the generation of hemoglobin and erythrocyte, and promote the release of bone marrow reticulocytes into blood. 37 As mentioned above, therefore, it is necessary to make intensive research on the effect of ZIF-8 MOFs on these tissues and organs when they enter the blood, and to make further evaluation of blood compatibility of ZIF-8 MOFs in vivo .…”

“…Overall, the existing knowledge on the biocompatibility of the ZIF-8 MOFs is not consistent. [15][16][17][18][19] For example, Vasconcelos et al did not found signicant cytotoxicity of the ZIF-8 MOF crystals loading an anti-cancer drug (doxorubicin) towards three cell lines (NCI-H292; HT-29; and HL-60). 20 However, Tamames-Tabar et al 16 observed that the half maximum inhibitory concentrations (IC50) of ZIF-8 MOF on HeLa and J774 cells were 100 and 25 mg mL À1 , respectively.…”

Degradation kinetic study of ZIF-8 microcrystals with and without the presence of lactic acid

“…The results of the material characterization are consistent with several previous studies. [48][49][50] Degradation of ZIF-8 in water, PBS, and 0.9% saline solutions…”

Nine days extended release of adenosine from biocompatible MOFs under biologically relevant conditions

“…18,22 The XRD pattern recorded for ZIF-8 demonstrated high crystallinity as judged by its diffraction pattern with characteristic sharp peaks at 2θ = 7.17°, 10.2°, 12.67°and 17.8°. 23 The isolated MOFs demonstrated permanent microporosity as shown from the corresponding N 2 sorption isotherms, Fig. 1c.…”