Copper release by MOF-74(Cu): a novel pharmacological alternative to diseases with deficiency of a vital oligoelement.

Copper deficiency can trigger various diseases such as Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD) and even compromise the development of living beings, as manifested in Menkes disease (MS). Thus, the regulated administration (controlled release) of copper represents an alternative to reduce neuronal deterioration and prevent disease progression. Therefore, we present, to the best of our knowledge, the first experimental in vitro investigation for the kinetics of copper release from MOF-74(Cu) and its distribution in vivo after oral administration in male Wistar rats. Taking advantage of the abundance and high periodicity of copper within the crystalline-nanostructured metal-organic framework material (MOF-74(Cu)), it was possible to control the release of copper due to the partial degradation of the material. Thus, we simultaneously corroborated a low accumulation of copper in the liver (the main detoxification organ) and a slight increase of copper in the brain (striatum and midbrain), demonstrating that MOF-74(Cu) is a promising pharmacological alternative (controlled copper source) to these diseases.

Copper(II)-MOFs for bio-applications.

The recent development and implementation of copper-based metal-organic frameworks in biological applications are reviewed. The advantages of the presence of copper in MOFs for relevant applications such as drug delivery, cancer treatment, sensing, and antimicrobial are highlighted. Advanced composites such as MOF-polymers are playing critical roles in developing materials for specific applications.

Linezolid@MOF-74 as a host-guest system with antimicrobial activity.

Linezolid (LNZ) is a new-generation synthetic molecule for the antibacterial treatment of severe infections, particularly in infective cases where the bacterial resistance to first-choice drugs is caused by Gram-positive pathogens. In this context, since 2009, some strains resistant to LNZ in patients with long-term treatments have been reported. Therefore, there is a need to use not only new drug molecules with antibacterial activities in the dosage form but also a different approach to pharmacotherapeutic strategies for skin infections, which lead to a reduction in the concentration of biocides. This work explores LNZ hosted at two isostructural MOFs, MOF-74(Zn) and MOF-74(Cu), as promising antimicrobial systems for gradual biocide release within 6 h. These systems reach a lower minimum inhibitory concentration (MIC) in comparison to free LNZ. Even a decreased MIC value is also observed, which is an encouraging result regarding the efficiency of the systems to control concentration-dependent antimicrobial resistance.

Sulfadiazine hosted in MIL-53(Al) as a biocide topical delivery system.

Sulfadiazine (SDZ), a bacteriostatic agent, was hosted in a metal-organic framework, specifically in MIL-53(Al) and modified-zinc MIL-53(Al,Zn). Materials were characterized structural, and texturally. Both hosts loaded sulfadiazine but they were differenced regarding the release of sulfadiazine. The presence of zinc plays a significant role to the modulation of sulfadiazine-MOF interactions. Release of sulfadiazine from sulfadiazine@MOFs was monitored in vitro and ex vivo conditions. A kinetic release model is proposed for in vitro sulfadiazine release. Remarkably, the materials did not show cytotoxicity against eukaryote cells.

Controlled Transdermal Release of Antioxidant Ferulate by a Porous Sc(III) MOF.

The Sc(III) MOF-type MFM-300(Sc) is demonstrated in this study to be stable under physiological conditions (PBS), biocompatible (to human skin cells), and an efficient drug carrier for the long-term controlled release (through human skin) of antioxidant ferulate. MFM-300(Sc) also preserves the antioxidant pharmacological effects of ferulate while enhancing the bio-preservation of dermal skin fibroblasts, during the delivery process. These discoveries pave the way toward the extended use of Sc(III)-based MOFs as drug delivery systems (DDSs).