Comprehensive Review on the Degradation Chemistry and Toxicity Studies of Functional Materials.

In recent decades there has been growing interest of material chemists in the successful development of functional materials for drug delivery, tissue engineering, imaging, diagnosis, theranostic, and other biomedical applications with advanced nanotechnology tools. The efficacy and safety of functional materials are determined by their pharmacological, toxicological, and immunogenic effects. It is essential to consider all degradation pathways of functional materials and to assess plausible intermediates and final products for quality control. This review provides a brief insight into chemical degradation mechanisms of functional materials like oxidation, photodegradation, and physical and enzymatic degradation. The intermediates and products of degradation were confirmed with analytical methods such as proton nuclear magnetic resonance (H NMR), gel permeation chromatography (GPC), UV-vis spectroscopy (UV-vis), infrared spectroscopy (IR), differential scanning calorimetry (DSC), mass spectroscopy, and other sophisticated analytical methods. These analytical methods are also used for regulatory, quality control, and stability purposes in industry. The assessment of degradation is important to predetermine the behavior of functional materials in specific storage conditions and can be relevant to their behavior during in vivo applications. Another important aspect is the evaluation of the toxicity of functional materials. Toxicity can be accessed with various methods using in vitro, in vivo, ex vivo, and in silico models. In vitro cell culture methods are used to determine mitochondrial damage, reactive oxygen species, stress responses, and cellular toxicity. In vitro cellular toxicity can be measured by MTT assay, LDH leakage assay, and hemolysis. In vivo studies are performed using various animal models involving zebrafish, rodents (mice and rats), and nonhuman primates. Ex vivo studies are also used for efficacy and toxicity determinations of functional materials like ex vivo potency assay and precision-cut liver slice (PCLS) models. The in silico tools with computational simulations like quantitative structure-activity relationships (QSAR), pharmacokinetics (PK) and pharmacodynamics (PD), dose and time response, and quantitative cationic-activity relationships ((Q)CARs) are used for prediction of the toxicity of functional materials. In this review, we studied the principle methods used for degradation studies, different degradation pathways, and mechanisms of functional material degradation with prototype examples. We discuss toxicity assessments with different toxicity approaches used for estimation of the safety and efficacy of functional materials.