Restricted accessResearch articleFirst published online 2025-1
γ-Cyclodextrin-metal organic framework as a carrier for trans-N-p-coumaroyltyramine: A study of drug solubability,stability,and inhibitory activity against α-glucosidase
γ-Cyclodextrin-based metal-organic frameworks (γ-CD-MOF) were successfully synthesized using the solvent diffusion method and applied as carriers for trans-N-p-coumaroyltyramine (N-p-t-CT, NCT) to study the solubability, stability, sustained release and inhibitory activity against α-glucosidase. The solubilization effect of γ-CD-MOF on N-p-t-CT was performed using impregnation (NCT@CD-MOF-1) and co-crystallization (NCT@CD-MOF-2) methods. X-ray diffraction, scanning electron microscope (SEM), fourier transform infrared spectrometer (FTIR), and N2 adsorption/desorption were used to characterize the MOFs before and after loading NCT. The results showed that NCT@CD-MOF-2 had a better solubability for N-p-t-CT, 145.03 μg/mg of drug loading capacity could be achieved, and the solubility of NCT@CD-MOF-2 in water was 366 times higher than free N-p-t-CT. In addition, the stabilities of N-p-t-CT under temperature, UV light and pH conditions were greatly improved after encapsulation in γ-CD-MOF. Furthermore, NCT@CD-MOFs had a sustained release of N-p-t-CT over an extended period in vitro due to the primary encapsulation in pore structures. Notably, γ-CD-MOF loaded with N-p-t-CT showed superior inhibitory activity against α-glucosidase compared to free N-p-t-CT. Cytotoxicity studies demonstrated that NCT@CD-MOF-2 had low toxicity in vitro and perfect biocompatibility with HL-7702 cells, and γ-CD-MOF could reduce the toxicity of free N-p-t-CT at higher concentrations.
GaoKMaDChengY, et al.Three new dimers and two monomers of phenolic amides from the fruits of Lycium barbarum and their antioxidant activities. J Agric Food Chem2015; 63: 1067–1075. DOI: 10.1021/jf5049222.
2.
ZhangLBaiBLiuX, et al.α-Glucosidase inhibitors from Chinese Yam (Dioscorea opposita Thunb). Food Chem2011; 126: 203–206. DOI: 10.1016/j.foodchem.2010.10.100.
3.
LiWJChengXLLiuJ, et al.Phenolic compounds and antioxidant activities of Liriope muscari. Molecules2012; 17: 1797–1808. DOI: 10.3390/molecules17021797.
4.
DaeKKLeeK. Inhibitory effect of Trans-N-p-coumaroyl tryamine from the twigs of Celtis chinensis on the acetylcholinesterase. Arch Pharm Res2003; 26: 735–738. DOI: 10.1007/bf02976684.
5.
NishiokaTWatanabeJKawabataJet al. (1997) Isolation and activity of N-p-Coumaroyltyramine, an (α-Glucosidase inhibitor in Welsh onion (Allium fistulosum). 61:1138–1141.
6.
CelebiogluAYildizZIUyarT. Fabrication of electrospun eugenol/cyclodextrin inclusion complex nanofibrous webs for enhanced antioxidant property, water solubility, and high temperature stability. J Agric Food Chem2018; 66: 457–466. DOI: 10.1021/acs.jafc.7b04312.
7.
ZacchignaMDi LucaGMaurichV, et al.Syntheses, chemical and enzymatic stability of new poly(ethylene glycol)–acyclovir prodrugs. Farm2002; 57: 207–214. DOI: 10.1016/S0014-827X(01)01193-4.
8.
YaghiOMRichardsonDALiG, et al.Prepared from clusters and metal-organic building blocks. Mat Res Soc1995; 371: 15–19.
RajkumarTKukkarDKimKH, et al.Cyclodextrin-metal–organic framework (CD-MOF): from synthesis to applications. J Ind Eng Chem2019; 72: 50–66. DOI: 10.1016/j.jiec.2018.12.048.
11.
LiLWangJZhangZ, et al.Inverse adsorption separation of CO2/C2 H2 mixture in cyclodextrin-based metal-organic frameworks. ACS Appl Mater Interfaces2019; 11: 2543–2550. DOI: 10.1021/acsami.8b19590.
12.
JensenSTanKLustigW, et al.Quenching of photoluminescence in a Zn-MOF sensor by nitroaromatic molecules. J Mater Chem C2019; 7: 2625–2632. DOI: 10.1039/c8tc06281a.
13.
WangTGaoLHouJ, et al.Rational approach to guest confinement inside MOF cavities for low-temperature catalysis. Nat Commun2019; 10: 1340. DOI: 10.1038/s41467-019-08972-x.
14.
WangYJinHMaQ, et al.A MOF glass membrane for gas separation. Angew Chem Int Ed Engl2020; 59: 4365–4369. DOI: 10.1002/anie.201915807.
15.
WangYWuWMaoD, et al.Metal–organic framework assisted and tumor microenvironment modulated synergistic image-guided photo-chemo therapy. Adv Funct Mater2020; 30: 2002431. DOI: 10.1002/adfm.202002431.
16.
DingYXuHXuC, et al.A nanomedicine fabricated from gold nanoparticles-decorated metal–organic framework for cascade chemo/chemodynamic cancer therapy. Adv Sci (Weinh)2020; 7: 2001060. DOI: 10.1002/advs.202001060.
17.
SmaldoneRAForganRSFurukawaH, et al.Metal-organic frameworks from edible natural products. Angew Chem Int Ed Engl2010; 49: 8630–8634. DOI: 10.1002/anie.201002343.
18.
RoyIStoddartJF. Cyclodextrin metal-organic frameworks and their applications. Acc Chem Res2021; 54: 1440–1453. DOI: 10.1021/acs.accounts.0c00695.
19.
HamediAAnceschiAPatruccoA, et al.A γ-cyclodextrin-based metal–organic framework (γ-CD-MOF): a review of recent advances for drug delivery application. J Drug Target2022; 30: 381–393. DOI: 10.1080/1061186X.2021.2012683.
20.
HanYLiuWHuangJ, et al.Cyclodextrin-based metal-organic frameworks (CD-MOFs) in pharmaceutics and biomedicine. Pharmaceutics2018; 10: 271. DOI: 10.3390/pharmaceutics10040271.
21.
ChenYTaiKMaP, et al.Novel γ-cyclodextrin-metal–organic frameworks for encapsulation of curcumin with improved loading capacity, physicochemical stability and controlled release properties. Food Chem2021; 347: 128978. DOI: 10.1016/j.foodchem.2020.128978.
22.
QiuCMcClementsDJJinZ, et al.Development of nanoscale bioactive delivery systems using sonication: glycyrrhizic acid-loaded cyclodextrin metal-organic frameworks. J Colloid Interface Sci2019; 553: 549–556. DOI: 10.1016/j.jcis.2019.06.064.
23.
BernelaMAhujaMThakurR. Enhancement of anti-inflammatory activity of glycyrrhizic acid by encapsulation in chitosan-katira gum nanoparticles. Eur J Pharm Biopharm2016; 105: 141–147. DOI: 10.1016/j.ejpb.2016.06.003.
24.
ShakyaSHeYRenX, et al.Ultrafine silver nanoparticles embedded in cyclodextrin metal-organic frameworks with GRGDS functionalization to promote antibacterial and wound healing application. Small2019; 15: e1901065. DOI: 10.1002/smll.201901065.
25.
HeYZhangWGuoT, et al.Drug nanoclusters formed in confined nano-cages of CD-MOF: dramatic enhancement of solubility and bioavailability of azilsartan. Acta Pharm Sin B2019; 9: 97–106. DOI: 10.1016/j.apsb.2018.09.003.
26.
HuXWangCWangL, et al.Nanoporous CD-MOF particles with uniform and inhalable size for pulmonary delivery of budesonide. Int J Pharm2019; 564: 153–161. DOI: 10.1016/j.ijpharm.2019.04.030.
27.
LiXGuoTLachmanskiL, et al.Cyclodextrin-based metal-organic frameworks particles as efficient carriers for lansoprazole: study of morphology and chemical composition of individual particles. Int J Pharm2017; 531: 424–432. DOI: 10.1016/j.ijpharm.2017.05.056.
28.
LiH. Cis-trans Isomerization and Solubilization of Trans-N-p-coumaroyltyramine. Master thesis. Henan University, Kaifeng, 2018.
29.
LiHLvNLiX, et al.Composite CD-MOF nanocrystals-containing microspheres for sustained drug delivery. Nanoscale2017; 9: 7454–7463. DOI: 10.1039/C6NR07593B.
30.
TseJYKadotaKNakajimaT, et al.Crystalline rearranged CD-MOF particles obtained via spray-drying synthesis applied to inhalable formulations with high drug loading. Cryst Growth Des2022; 22: 1143–1154. DOI: 10.1021/acs.cgd.1c01091.
31.
ChenXGuoTZhangK, et al.Simultaneous improvement to solubility and bioavailability of active natural compound isosteviol using cyclodextrin metal-organic frameworks. Acta Pharm Sin B2021; 11: 2914–2923. DOI: 10.1016/j.apsb.2021.04.018.
32.
HuWCaoGZhuJ, et al.Naturally occurring Batatasins and their derivatives as α-glucosidase inhibitors. RSC Adv2015; 5: 82153–82158. DOI: 10.1039/C5RA15328J.
33.
ZhangSWuDLiH, et al.Rapid identification of α-glucosidase inhibitors from Dioscorea opposita Thunb peel extract by enzyme functionalized Fe3O4 magnetic nanoparticles coupled with HPLC-MS/MS. Food Funct2017; 8: 3219–3227. DOI: 10.1039/C7FO00928C.
34.
ShiYWangYZhuJ, et al.Molecularly imprinting polymers (MIP) based on nitrogen doped carbon dots and MIL-101(Fe) for doxorubicin hydrochloride delivery. Nanomaterials2020; 10: 1655. DOI: 10.3390/nano10091655.
35.
YoshiharaTTakamatsuSSakamuraS. Three new phenolic amides from the roots of Eggplant (Solanum melongena L.). Agric Biol Chem1978; 42: 623–627.
36.
MangolimCSMoriwakiCNogueiraAC, et al.Curcumin-β-cyclodextrin inclusion complex: stability, solubility, characterisation by FT-IR, FT-Raman, X-ray diffraction and photoacoustic spectroscopy, and food application. Food Chem2014; 153: 361–370. DOI: 10.1016/j.foodchem.2013.12.067.
37.
ZhaoGHuiYRupprechtJK, et al.Additional bioactive compounds and trilobacin, a novel highly cytotoxic acetogenin, from the bark of Asimina triloba. J Nat Prod1992; 55: 347–356.
38.
InoueYNanriAMurataI, et al.Characterization of inclusion complex of coenzyme Q10 with the new carrier CD-MOF-1 prepared by solvent evaporation. AAPS PharmSciTech2018; 19: 3048–3056. DOI: 10.1208/s12249-018-1136-7.
39.
HeYXuJSunX, et al.Cuboidal tethered cyclodextrin frameworks tailored for hemostasis and injured vessel targeting. Theranostics2019; 9: 2489–2504. DOI: 10.7150/thno.31159.
40.
YangALiuHLiZ, et al.Green synthesis of β-cyclodextrin metal–organic frameworks and the adsorption of quercetin and emodin. Polyhedron2019; 159: 116–126. DOI: 10.1016/j.poly.2018.11.043.
41.
AnovitzLMColeDR. Characterization and analysis of porosity and pore structures. Rev Mineral Geochem2015; 80: 61–164. DOI: 10.2138/rmg.2015.80.04.
42.
SinghMPilaniS. Review: in vitro drug release characterization models. Int J Pharm Stud Res2021; 2: 77–84.
43.
RitgerPLPeppasNA. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release1987; 5: 37–42. DOI: 10.1016/0168-3659(87)90035-6.
44.
AdepuSKhandelwalM. Ex-situ modification of bacterial cellulose for immediate and sustained drug release with insights into release mechanism. Carbohydr Polym2020; 249: 116816. DOI: 10.1016/j.carbpol.2020.116816.
45.
SaxenaAKalotiMBohidarHB. Rheological properties of binary and ternary protein-polysaccharide co-hydrogels and comparative release kinetics of salbutamol sulphate from their matrices. Int J Biol Macromol2011; 48: 263–270. DOI: 10.1016/j.ijbiomac.2010.11.008.
46.
ICH Harmonized Tripartite Guideline. Stability testing photostability testing of new drug substances and products. 1996.
47.
TangSF. The foundations of ICH harmonized guideline on photostability test and the comparison with the Chinese guideline. Chin Drug Standard2002; 3(3): 6–9.
48.
van de LaarFALucassenPLAkkermansRP, et al.Alpha-glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis. Diabetes Care2005; 28: 154–163. DOI: 10.2337/diacare.28.1.154.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
