**Bio-Inspired Metal-Organic Frameworks in the Pharmaceutical World: A Brief Review**

Vânia André and Sílvia Quaresma

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64027

#### **Abstract**

One of the great challenges in the pharmaceutical industry is the search for more efficient and cost-effective ways to store and deliver existing drugs. Bio-inspired metalorganic frameworks (BioMOFs) are groundbreaking materials that have recently been explored for drug storage, delivery and controlled release as well as for applications in imaging and sensing for therapeutic and diagnostic. This review presents a brief overview on these materials, and by alluding to a few reported examples, it intends to clearly show the extremely important role that BioMOFs have been playing in the pharmaceutical field.

**Keywords:** BioMOFs, drugs, ZIFs, smart drug delivery

## **1. Introduction**

The development of new solid forms of pharmaceuticals is of utmost importance in modern science as they present a single opportunity to modify the properties of active pharmaceutical ingredients (API) without interfering with its biological role. The influence of the crystal forms is very wide and diverse, changing not only the solid-state characteristics (density, habit, shape, colour, stability, melting point) but also properties that might affect their function (dissolu‐ tion rate, solubility, stability to temperature and humidity, thermal properties, moisture uptake, bioavailability, pharmacokinetics) and even some industrial aspects of formulation (flowabil‐ ity, mixability, stress stability, granulation, encapsulation, tabletting). The combination of crystal engineering and supramolecular chemistry principles allows the design and synthesis of smartly designed drugs with tailor-made properties, keeping their pharmacological properties, and thus presenting major advantages, including reduced time for introduction in the market [1–6].

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Consequently, the synthesis of new crystal forms evolved tremendously in the last decade, and the interest of pharmaceutical companies in the appearance/disappearance of new solid forms of APIs has vastly increased. Polymorphs, hydrates and salts of drugs are long-known forms with recognized impact in their properties. Cocrystals represent a more recent class of crystal forms that own particular scientific and regulatory advantages (FDA guidance is already available and cocrystals are now being commercialized as drugs in some countries). Many examples show their relevance in the pharmaceutical industry, most of them by enhancing stability, solubility and/or bioavailability of known drugs [7–20].

Likewise, nanoporous materials recently became of pertinent use in the medicinal and pharmacological fields for drug storage, delivery and controlled release in addition to applications in imaging and sensing for therapeutic and diagnostic [21–34]. Particularly, metal organic frameworks (MOFs) have generated large interest owing to their versatile architectures [35] and their promising applications not only in ion exchange, adsorption and gas storage [36– 41], separation processes [42], heterogeneous catalysis [43, 44], polymerization reactions [45, 46], luminescence [47], non-linear optics [48] and magnetism [49], but also as drug carriers, systems for drug delivery [22, 23, 50, 51], contrast agents for magnetic resonance imaging (MRI) [21] and systems with potential use in other biomedical applications [23].

Up to now, drug delivery from porous solids has been achieved by encapsulation in mesopo‐ rous silicas or zeolites, methods that are strongly dependent on the pore size and on the hostguest interactions. Both hypotheses suffer from important drawbacks: low drug-storage capacity, too rapid delivery and solid degradation that brings toxicity concerns [23, 25, 26, 28, 29, 52]. Extended metal-ligand networks with metal nodes and bridging organic ligands such as coordination networks, porous coordination networks (PCNs), porous coordination polymers (PCPs) and MOFs have attracted great attention in the last years [24, 25, 28, 53, 54]. Particularly, MOFs with biological-friendly composition emerged as new drug carriers capable of tackling these problems [21, 23, 25, 26, 28, 29, 55, 56].

In fact, MOFs are among the most exciting architectures in nanotechnology and are defined as hybrid self-assemblies of metal ions or metal clusters (coordination centres) and organic fragments (linkers). They exhibit some of the highest porosities known, turning them into ideal materials for capture, storage and/or delivery applications [21, 24–26, 29, 54, 57]. Compared to other nanocarriers, MOFs are candidates to extensive applications since they combine high pore volume with a regular porosity, and the presence of tuneable organic groups allows an easy modulation of the framework as well as of the pore size [22, 24–26].

The first families of MOFs considered as potential drug delivery systems were the coordination polymers from Oslo (CPO), such as CPO-27(Mg) [58] built up from magnesium coordination polymers, and the materials of Institute Lavoisier (MIL) [22]. Horcajada et al. [22, 23] prepared MIL-100 (with trimesic acid) and MIL-101 (with terephthalic acid) applied for the delivery of ibuprofen in the gastrointestinal tract, exhibiting high drug-storage capacity and a complete drug-controlled release under physiological conditions [22, 23]. Less toxic systems, using iron and more flexible MILs, are under study [25], and the first biodegradable therapeutic MOF, BioMIL-1, was reported by Miller et al. in 2010 [27]. The large breathing effect that MOFs can attain is another particularly interesting feature for potential applications in drug delivery [54, 59, 52].

Zeolite-like MOFs (ZMOFs) are a unique subset of MOFs with exceptional characteristics arising from the periodic pore systems and distinctive cage-like cavities, in conjunction with modular intra- and/or extra-framework components [60–62]. Zeolitic imidazolate frameworks (ZIFs) are a special class of ZMOFs comprising imidazolate linkers and metal ions. ZIFs simultaneously have the following characteristics of MOFs and zeolites, combining the advantages of both: ultrahigh surface areas, unimodal micropores, high crystallinity, various functionalities and exceptional thermal and chemical stabilities, making them very promising for biomedical applications [63, 64]. Several studies describe the successful incorporation of anticancer drugs into ZIF-8 with positive results for the controlled pH-sensitive drug release and fluorescence imaging [65–69]. Also caffeine was already encapsulated into ZIF-8 showing a controlled release [70, 71].

The scope of this brief review focuses on presenting some aspects on the BioMOFs preparation, and a few examples of promising bioapplications of MOFs, including ZIFs.
