Cyclodextrin-Based Metal-Organic Frameworks (CD-MOFs) in Pharmaceutics and Biomedicine

Abstract

Metal-organic frameworks (MOFs) show promising application in biomedicine and pharmaceutics owing to their extraordinarily high surface area, tunable pore size, and adjustable internal surface properties. However, MOFs are prepared from non-renewable or toxic materials, which limit their real-world applications. Cyclodextrins (CDs) are a typical natural and biodegradable cyclic oligosaccharide and are primarily used to enhance the aqueous solubility, safety, and bioavailability of drugs by virtue of its low toxicity and highly flexible structure, offering a peculiar ability to form CD/drug inclusions. A sophisticated strategy where CD is deployed as a ligand to form an assembly of cyclodextrin-based MOFs (CD-MOFs) may overcome real-world application drawbacks of MOFs. CD-MOFs incorporate the porous features of MOFs and the encapsulation capability of CD for drug molecules, leading to outstanding properties when compared with traditional hybrid materials. This review focuses on the inclusion technology and drug delivery properties associated with CD-MOFs. In addition, synthetic strategies and currently developed uses of CD-MOFs are highlighted as well. Also, perspectives and future challenges in this rapidly developing research area are discussed.

Keywords: CD-MOFs; applications; drug delivery; inclusion technology.

Figure 1

Structural representations of three types of cyclodextrins (CDs) and a schematic diagram of coordination between α/β/γ CDs and metal ions. (A) The [K₆ (CD)₂] dimer torus. (B) View of two pairs of β-CD molecules combined with the individual Cs⁺ ion; they have the reverse packing arrangement. (C) (γ-CD)₆ cube of CD-MOFs. Reprinted with permission from [61,62,63,64], Copyright ACS, 2011; RSC, 2017; RSC, 2017; and RSC, 2016.

Figure 2

The three synthetic routes of CD-MOFs. (A) the schematic representation of γ-CD-MOF synthesis by vapor diffusion method, (B) the different sizes of γ-CD-MOF were adjusted under the microwave method, (C) the schematic view of different structural formation of CD-MOF by using different templates in the reaction process. Reprinted with permission from [63,78,80], copyright RSC, 2017; ACS, 2017; and Elsevier, 2017.

Figure 3

The drug release curve of three CD-MOFs in different pH solutions (A) and morphologies of CD-MOFs in different sizes (B). Reprinted with permission from [58,66], copyright Elsevier, 2018 and Wiley, 2012.

Figure 4

Time dependence of five drug adsorption capacities in α-CD (left) and Na-α-CD-MOF (right) (A), 5-Fu drug-loading rate in α-CD and two α-CD-MOFs (B), and four sulfonamide drug adsorption rates in γ-CD-MOF (C). Reprinted with permission from [64,69,99], copyright RSC, 2016; Elsevier, 2017; and Elsevier, 2018.

Figure 5

(A) Chart of cytotoxicity on HepG2 cells for α-CD, Na-α-CD-MOF, 5-FU (left), MTX (right), 5-FU-α-CD (left), MTX-α-CD (right), 5-FU-Na-α-CD-MOF (left), and MTX-Na-α-CDMOF (right). (B) Cytotoxic effect of three γ-CD-MOFs at a concentration of 62.5–2000 μg/mL: (left) HepG2 cell lines and (right) Caco-2 cell lines. Reprinted with permission from [58,69], copyright Elsevier, 2018 and Elsevier, 2017.

Figure 6

Illustration of burst and sustained drug release mechanisms of γ-CD complexes and CD-MOFs within PAA matrix. Reprinted with permission from [84], Copyright RSC, 2017.

Figure 7

Illustration of CD-MOFs loading drugs. (A) Lansoprazole, (B) curcumin, and (C) ibuprofen loaded by CD-MOFs. Reprinted with permission from [80,88,91], copyright Elsevier, 2017; ACS, 2017; Elsevier, 2016.