Metal-organic frameworks (MOFs), comprised of organic ligands and metal ions/metal clusters
via
coordinative bonds are highly porous, crystalline materials. Their tunable porosity, chemical composition, size and shape, and easy surface functionalization make this large family more and more popular for drug delivery. There is a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applications. This article presents an overall review and perspectives of MOFs-based drug delivery systems (DDSs), starting with the MOFs classification adapted for DDSs based on the types of constituting metals and ligands. Then, the synthesis and characterization of MOFs for DDSs are developed, followed by the drug loading strategies, applications, biopharmaceutics and quality control. Importantly, a variety of representative applications of MOFs are detailed from a point of view of applications in pharmaceutics, diseases therapy and advanced DDSs. In particular, the biopharmaceutics and quality control of MOFs-based DDSs are summarized with critical issues to be addressed. Finally, challenges in MOFs development for DDSs are discussed, such as biostability, biosafety, biopharmaceutics and nomenclature.
Due
to the complexity of multifactorial diseases, single-target
drugs do not always exhibit satisfactory efficacy. Recently, increasing
evidence indicates that simultaneous modulation of multiple targets
may improve both therapeutic safety and efficacy, compared with single-target
drugs. However, few multitarget drugs are on market or in clinical
trials, despite the best efforts of medicinal chemists. This article
discusses the systematic establishment of target combination, lead
generation, and optimization of multitarget-directed ligands (MTDLs).
Moreover, we analyze some MTDLs research cases for several complex
diseases in recent years and the physicochemical properties of 117
clinical multitarget drugs, with the aim to reveal the trends and
insights of the potential use of MTDLs.
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