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ACS Appl Mater Interfaces ; 13(1): 312-323, 2021 Jan 13.
Article in English | MEDLINE | ID: covidwho-997781

ABSTRACT

In this study, we present a modulated synthesis nanocrystalline defective UiO-66 metal-organic framework as a potential chloroquine diphosphate (CQ) delivery system. Increasing the concentration of hydrochloric acid during the modulated synthesis resulted in a considerable increase of pore volume, which enhanced the CQ loading in CQ@UiO-66 composites. Drug release tests for CQ@UiO-66 composites have confirmed prolonged CQ release in comparison with pure CQ. In vivo tests on a Danio reiro model organism have revealed that CQ released from CQ@UiO-66 25% showed lower toxicity and fewer cardiotoxic effects manifested by cardiac malformations and arrhythmia in comparison to analogous doses of CQ. Cytotoxicity tests proved that the CQ loaded on the defective UiO-66 cargo resulted in increased viability of cardiac cells (H9C2) as compared to incubation with pure CQ. The experimental results presented here may be a step forward in the context of reducing the cardiotoxicity CQ.


Subject(s)
Chloroquine/analogs & derivatives , Heart Diseases/drug therapy , Metal-Organic Frameworks/pharmacology , Nanoparticles/chemistry , Animals , Chloroquine/adverse effects , Chloroquine/chemistry , Chloroquine/pharmacology , Disease Models, Animal , Drug Delivery Systems/adverse effects , Drug Liberation/drug effects , HEK293 Cells , Heart Diseases/chemically induced , Heart Diseases/pathology , Humans , Hydrochloric Acid/pharmacology , Metal-Organic Frameworks/chemistry , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Phthalic Acids/chemistry , Phthalic Acids/pharmacology , Zebrafish/genetics
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