Application of the MOFs-Drug Delivery System

Metal Organic Frameworks (MOFs) are constructed by metal ions/clusters and multidentate organic linkers via coordination bonds (reticular synthesis) have significantly enriched the domain of porous materials [1,2]. Based on the flexibility of the constituents, geometry, size and functionality, MOFs with a crystalline nature possess extremely high surface areas (typically ranging from 1000 to 10,000 m² g^-1) and tunable pore sizes/characteristics. These aspects endow MOFs with fantastic functionalities/properties for a variety of applications such as gas adsorption, separation, catalysis, sensors, drug delivery, proton conduction etc [2].

In the de novo synthesis of MOFs, ligands with relatively high pKa (e.g. azoles) easily produce robust frameworks with low-valent metal ions, while linkers with relatively low pKa (e.g. carboxylic acids) tend to bind with high-valent metal ions to give stable structures. In general, dense and rigid frameworks are constructed by rigid and highly connected building blocks (metal ions/clusters and ligands) which usually demonstrate a high stability due to their high tolerance towards partial lattice collapse [3]. Surface hydrophobicity prevents the adsorption of water into pores and/or the condensation of water around the metal clusters, which enhances the MOF stability in the presence of water [4].

Scheme 1. Schematic illustration showing stable MOFs composed of metal clusters, organic linkers and dangling functional groups [1].

Over the past two decades, various promising methods have been developed to tune MOF stability, especially chemical stability, which might be the most important and significant prerequisite of MOFs for their diverse applications [3]. Therefore, we believe that it is a good time for us to provide a systematic review of recent advances in the preparation of stable MOFs and their applications (Scheme 1). Our discussions begin with a summary of strategies that have been developed for enhancing the chemical stability of MOFs while emphasizing the key factors in the synthesis of stable MOFs and MOF-based materials. Next, the unique attributes of stable MOFs and their extensive applications, including adsorption and separation, heterogeneous catalysis, fluorescence sensing, biological and medical application, and proton conductivity, are been discussed by Ding et al. [1]. But we choose drug delivery from Ding et al., for medical application. Hopefully, this content will inspire the scientists in chemistry and materials science and interdisciplinary researchers towards this field.

Medical (Drug delivery) applications

MOFs are extensively used in biological and medical applications such as biosensing, drug release, biomimetic catalysis, etc. [5] for their tunable pore sizes, high surface area, and versatile physical and chemical properties. MOFs with excellent chemical stability is very essential for these applications. They should possess strong resistance to hydrolysis/collapse in physiological environments in which they could be expected to function, e.g. stomach acidity, intestinal alkalinity and the peristalsis in the esophagus, stomach, and intestines.

As an early attempt, the use of MOFs for drug release, two flexible frameworks, MIL-53(Cr) and MIL-53(Fe), were selected as carrier systems for delivering ibuprofen [6]. Due to the unique flexibility, a very slow and complete release of ibuprofen over a period of three weeks was accomplished with both MIL-53(Cr) and MIL-53(Fe). Deng's group revealed that the guest release rate was strongly correlated with the type and proportion of functional groups in MOFs [7]. By constructing different multivariate MOFs from MIL-101(Fe), the maximum release amount of doxorubicin (DOX) could be shifted from 17^th to 29^th day within a 40 day release period. In order to improve the biocompatibility of carriers, adenine was employed as a biomolecular ligand to fabricate an ionic framework, bioMOF-1, which could maintain the structural integrity in biological buffers for weeks [8]. Unlike common MOFs, the release of procainamide from bio-MOF-1 could be triggered by the ionic interactions between the drug and the framework. Recently, Farha's group demonstrated the immobilization of insulin in an acid stable MOF, NU-1000 [9]. By virtue of the protective effect from NU-1000, insulin was stable even upon exposure to stomach acid (pH = 1.5–3.5) and pepsin (Fig. 1). Moreover, 40 wt% of insulin could be released from the host framework under simulated physiological conditions (pH = 7.0) (Figure 1).

Figure 1: Schematic illustration of encapsulation of insulin in themesopores (32 Å) of NU-1000 and exclusion of pepsin from the MOF framework [1].

Nevertheless, the study of MOFs and MOF-based materials for biological and medical applications is still in its infancy. One remaining critical issue is the fabrication of nontoxic MOFs with outstanding chemical stability, excellent biocompatibility, and appropriate pore size and pore volume. 

Our SNB team recommended this research article to help the readers to know that the MOFs are extensively used in biomedical applications particularly for drug delivery.In addition, control of MOF particle size is also very important in view of the endocytosis by the living cells and systemic circulation in blood. As for drug delivery, the degradation mechanism of MOFs should be studied closely before the  in vivo investigations and other clinical applications.

References

1. M. Ding et al., Chem. Sci., 10, 10209 (2019).
2. H. C. Zhou et al., Chem. Soc. Rev., 43, 5415 (2014).
3. S. Yuan, et al., Adv. Mater., 30, 1704303 (2018).
4. N. C. Burtch, et al., Chem. Rev., 114, 10575 (2014).
5. J. S. Qin, et al., Chem. Commun., 54, 4231 (2018).
6. P. Horcajada, et al., J. Am. Chem. Soc., 130, 6774 (2008).
7. Z. Dong, et. al., J. Am. Chem. Soc., 139, 14209 (2017).
8. J. An, et al., J. Am. Chem. Soc., 131, 8376 (2009).
9. Y. Chen, et al., J. Am. Chem. Soc., 140, 5678 (2018).

Blog Written By

Dr. S. Thirumurugan

Assistant Professor

National College, Tiruchirappalli

Tamil Nadu, India

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Dr. A. S. Ganeshraja

Dr. S. Chandrasekar

Dr. K. Rajkumar

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Dr. Y. Sasikumar

Dr. K. Vaithinathan