Metal-organic frameworks (MOFs) are based on metals and organic linkers; they possess large surface areas, suitable pore size and shape, wide range of chemical composition, and functionalized pore surface, which enable them for possible applications as delivery vehicles for therapeutic agents. The challenges include not only the development of new solids but also continuous improvements in the formulation and processing of the materials, including modifying the morphology and shape of the frameworks to fit the proposed applications of drug delivery. This chapter discussed enormous MOF-based stimuli responsive drug delivery systems, and considerable achievements have been made as a new avenue for drug delivery, their structural aspects, their applications in the controlled release of the drugs, and future view for development of drug controlled release researches using MOFs. Among the properties that must be developed and approved are the materials' toxicology, stability, their reproducibility of manufacture of MOFs in body's liquid, and pharmacokinetics of drug-loaded MOFs.
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Drug delivery systems are one of the best applications for the treatment of human diseases and biomedical materials (Gupta et al., 2012; Torchilin, 2005; Vallet-Regí et al., 2007; Yoo & Lee, 2006). In the field of drug delivery, looking for non-toxic carriers for drugs delivery to the body is a challenge (Davis et al., 2008; Dyson & Sava, 2006; Fathabadi et al., 2012). To solve these problems, metal organic frameworks (MOFs) are used as carriers for biomedical applications. The features of MOFs offer great chance for their uses as drug carriers, as high porosity, adjustable size and high loading capacity, which make it possible to use these frameworks in therapeutic projects such as drug delivery(Haydar et al., 2017), but also some properties need to be improves: toxicology of materials for use in healthcare applications. MOFs are required some conditions to have easier engineering the surface of materials to control in vivo fate such as controllable degradation of the solids, efficient encapsulation of therapeutic drugs with high loading amounts, controllable release of encapsulated cargos (Horcajada et al., 2010) and non-toxic building blocks, so chromium, cadmium, nickel, cobalt, and other metals are not suitable due to their high toxicity, some metals exist in appreciable amounts in the body, for example, iron is an main component of hemoglobin and is approximately 22 mM in blood plasma (Bertini, 2007) and also, Ca, Cu, Mn, Mg, Zn, Fe, Ti, their toxicity are determined by oral lethal dose LD50, Ca, 1 g/kg; Cu, 25 μg/kg; Mn, 1.5 g/kg; Mg, 8.1 g/kg; Zn, 350 μg/kg; Fe, 30 g/kg; Ti, 25 g/kg and Zr. 4.1 g/kg (Horcajada et al., 2012). The toxicity data (LD50) for some organic linkers are 5 g/kg (terephthalic acid), 8.4 g/kg (trimesic acid), 5 g/kg (2,6 napthalenedicarboxylic acid), 1.13 g/kg (1-methylimidazole), 1.4 g/kg (2-methylimidazole), 5 g/kg (isonicotinic acid), and 1.6 g/kg (5-aminoisophthalic acid), which are accepted for bio application. In vivo toxicity tests of iron trimesic MIL-100 (MIL = Material Institut Lavoisier) and trimesic acid were performed through intravenous administrating to rats, a symmetrical cyclic oligosaccharide, g-cyclodextrin (g-CD), was considered as a ligand to synthesize two MOFs, [(g-CD) (KOH)2] and [(g-CD)(RbOH)2 (Smaldone et al., 2010).
MOFs are insoluble in water, (Burrows et al., 2013). The extent of solubility of the MOFs in water can be increased by modifying surface or introducing additional functionalities to MOFs such as, attaching water attracting ligands or polymers, water-soluble or water-adsorbing MOFs are being useful for the CR of water-soluble drug release ()
The structure of MOFs is more open and less dense than a zeolite, but their nature and the extent of their flexibility are not clearly understood (Fletcher et al., 2005). MOFs are anionic, and can be designed to obtain hydrophilic pores to carry either the positive or negative charges, and can be used to encapsulate the drugs that contain the opposite charges to MOFs (Huxford et al., 2010). MOFs have high drug loading capacity, and versatile functionality (An et al., 2009), and are efficient of releasing drug to a physiological medium related to their pore characteristics (McKinlay et al., 2010) as well as based on the extent of host-guest interactions that take place. A series of biological evaluations on MOFs were examined such as, biocompatibility, bio-toxicity, cellular uptakes, tissue responses, and intracellular drug delivery. If MOFs are effectively able to display cell targeting, diagnostic and therapeutic abilities along with biological or toxicological properties, then these MOFs could be useful for oncological or cancer treatments. Some MOFs were conjugated with targeting peptides to facilitate cell targeting and treatments through releasing the drugs in the targeted area, and the drugs were encapsulated. The size, shape and morphology of MOFs impact on their capacity of loading and releasing drugs, and their toxicity in a biological environment. The loading of drugs into MOFs takes long time, and large amount of drugs used to feed for loading, so the drug loading efficiencies of MOFs are low, and it varies from MOFs to MOFs (Cai et al., 2019). This chapter presents an overview of MOFs used in drug controlled release and also, illustrates the perspectives, insights, and critical reflections on the controlled release of drugs from MOFs, and the biological evaluations of MOFs being used in CR of drugs.