Combined Ibuprofen and Curcumin Delivery Using Mg-MOF-74 as a Single Nanocarrier

Abstract

Metal–organic frameworks (MOFs) have been extensively used as drug delivery platforms because of their considerable textural properties and physiochemical tunability. However, most medicinal treatments often administer multiple therapeutic pharmaceuticals simultaneously and combined drug delivery over a single MOF carrier has not been extensively developed. As such, in this study we implemented Mg-MOF-74, which is known to have rapid pharmacokinetic properties, for the combined delivery of ibuprofen and curcumin to demonstrate the proof-of-concept for dual-drug delivery over this previously unexplored MOF. To this end, 30 wt % total drug loading of two drugs was impregnated at various ratios (25:5 ibuprofen–curcumin, 20:5 ibuprofen–curcumin, 15:15 ibuprofen–curcumin, 10:20 ibuprofen–curcumin, and 5:25 ibuprofen–curcumin), and the drug delivery performance of the materials was assessed from 0 to 24 h in phosphate-buffered saline (PBS) solution using high-performance liquid chromatography (HPLC). The experiments revealed that all five ratios of ibuprofen–curcumin loadings can effectively deliver both compounds; however, elevating the curcumin loading beyond 10 wt % decreases the drug loading efficiency for ibuprofen and can also inhibit ibuprofen release. Nevertheless, because Mg-MOF-74 was able to successfully deliver both compounds, this study serves as a promising proof-of-concept for dual-drug delivery from a single MOF carrier. In this regard, the work demonstrated herein expands the use of MOFs for drug delivery applications and can be used to supplement drug administration via orally ingested tablets.

Drug Delivery on Mg-MOF-74: The Effect of Drug Solubility on Pharmacokinetics

“…Indeed, the textural properties summarized in Table corroborated these findings, given that the curcumin-loaded MOF became mostly nonporous even at 30 wt % drug loading. Similar effects were shown in our previous works and were somewhat expected given the differences in molecular sizes and solubilities of these drugs. ,,, In the context of how these differences in the drug loading mechanism would be expected to influence pharmacokinetic release rates, without even considering solubility, one would anticipate that curcumin would have the worst rates of diffusivity. The reason being that such total blockage of the MOF crystalline faces would render the Mg clusters to be less soluble, thereby causing the release profile to be mostly driven by the rate of single-layer effusion of the drug film. ,,, Given the large molecular size of curcuminoids coupled with their poor solubility in PBS, such a rate would be expected to be quite slow …”

“…Similar effects were shown in our previous works and were somewhat expected given the differences in molecular sizes and solubilities of these drugs. 8,15,24,25 In the context of how these differences in the drug loading mechanism would be expected to influence pharmacokinetic release rates, without even considering solubility, one would anticipate that curcumin would have the worst rates of diffusivity. The reason being that such total blockage of the MOF crystalline faces would render the Mg clusters to be less soluble, thereby causing the release profile to be mostly driven by the rate of single-layer effusion of the drug film.…”

“…The reason being that such total blockage of the MOF crystalline faces would render the Mg clusters to be less soluble, thereby causing the release profile to be mostly driven by the rate of single-layer effusion of the drug film. 8,15,24,25 Given the large molecular size of curcuminoids coupled with their poor solubility in PBS, such a rate would be expected to be quite slow. 18 To assess any changes in the crystallinity of Mg-MOF-74 after encapsulation of ibuprofen, 5-fluorouracil, and curcumin, XRD analysis was run on the bare MOF and drug-loaded samples, and the corresponding spectra are presented in Figure 3.…”

The unique opportunities of mechanosynthesis in green and scalable fabrication of metal–organic frameworks

“…A series of well-known MOF materials such as MILs, ZIFs, UiOs, HKUST-1, or MOF-74 have been widely used for biomedical applications. [167][168][169][170][171][172][173][174][175] In these cases, the Bio-MOF material can be obtained via an effective synthesis approach followed by in situ or ex situ encapsulation of the bioactive molecules within the MOF pores. The use of solvent-free mechanosynthesis strategies has revealed great advantages for in situ encapsulation of a wide variety of enzymes within the MOF pores.…”

Metal-based nano-delivery platform for treating bone disease and regeneration

“…Although further research is required to expand the contents of these MOFs on nano-drug delivery, these MOFs have been attracting increasing research attention in recent years. Mg MOFs have been demonstrated to effectively load small molecule drugs such as icariin ( Wang W. et al, 2022 ), ibuprofen, curcumin ( Lawson et al, 2022 ), alpha-cyano-4-hydroxycinnamate ( Hu J. Q. et al, 2021 ), and IL4 cytokines ( Zheng et al, 2020 ). Additionally, Co. MOFs were used to load drugs, enzymes, and bioactive molecules, such as dimethyloxalylglycine (DMOG) ( Li J. K. et al, 2020 ), olsalazine ( Levine et al, 2016 ), glucose oxidase ( Fang et al, 2020 ), and 4-chloro-N-cyclohexyl-N-(phenylmethyl)-benzamide ( Sun et al, 2022 ).…”