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Solvent-Free Loading of Vitamin A Palmitate into β-Cyclodextrin Metal-Organic Frameworks for Stability Enhancement

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Abstract

Cyclodextrin metal-organic frameworks (CD-MOFs) exhibit a high structural diversity, which contributes to their functional properties. In this study, we have successfully synthesized a novel type of β-cyclodextrin metal-organic framework (β-CD-POF(I)) that exhibits excellent drug adsorption capacity and enhances stability. Single-crystal X-ray diffraction analysis revealed that β-CD-POF(I) possessed the dicyclodextrin channel moieties and long-parallel tubular cavities. Compared with the reported β-CD-MOFs, the β-CD-POF(I) has a more promising drug encapsulation capability. Here, the stability of vitamin A palmitate (VAP) was effectively improved by the solvent-free method. Molecular modeling and other characterization techniques like synchrotron radiation Fourier transform infrared spectroscopy (SR-FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), and nitrogen adsorption isotherm were applied to confirm that the VAP was successfully encapsulated into the channel formed by the dicyclodextrin pairs. Furthermore, the mechanism of stability enhancement for VAP was determined to be due to the constraint and separation effects of β-CD pairs on VAP. Therefore, β-CD-POF(I) is capable of trapping and stabilizing certain unstable drug molecules, offering benefits and application possibilities.

Graphical abstract

One kind of cyclodextrin particle with characteristic shapes of dicyclodextrin channel moieties and parallel tubular cavities, which was synthesized by a facile process. Subsequently, the spatial structure and characteristics of the β-CD-POF(I) were primarily confirmed. The structure of β-CD-POF(I) was then compared to that of KOH-β-CD-MOF, and a better material for vitamin A palmitate (VAP) encapsulation was determined. VAP was successfully loaded into the particles by solvent-free method. The arrangement of spatial structure made cyclodextrin molecular cavity encapsulation in β-CD-POF(I) more stable for VAP capture than that of KOH-β-CD-MOF.

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References

  1. Forgan RS, Smaldone RA, Gassensmith JJ, Furukawa H, Cordes DB, Li Q, et al. Nanoporous carbohydrate metal-organic frameworks. J Ame Chem Soc. 2012;134(1):406–17.

    Article  CAS  Google Scholar 

  2. Li B, Wen HM, Zhou W, Chen B. Porous Metal-organic frameworks for gas storage and separation: what, how, and why? J Phys Chem Lett. 2014;5(20):3468–79.

    Article  CAS  PubMed  Google Scholar 

  3. Li X, Guo T, Lachmanski L, Manoli F, Menendez-Miranda M, Manet I, et al. Cyclodextrin-based metal-organic frameworks particles as efficient carriers for lansoprazole: study of morphology and chemical composition of individual particles. Int J Pharmaceut. 2017;531(2):424–32.

    Article  CAS  Google Scholar 

  4. Lv N, Guo T, Liu B, Wang C, Singh V, Xu X, et al. Improvement in thermal stability of sucralose by γ-Cyclodextrin metal-organic frameworks. Pharmaceut Res. 2017;34(2):269–78.

    Article  CAS  Google Scholar 

  5. Moussa Z, Hmadeh M, Abiad MG, Dib OH, Patra D. Encapsulation of curcumin in cyclodextrin-metal organic frameworks: dissociation of loaded CD-MOFs enhances stability of curcumin. Food Chem. 2016;212:485–94.

  6. Zhang G, Meng F, Guo Z, Guo T, Peng H, Xiao J, et al. Enhanced stability of vitamin A palmitate microencapsulated by γ-cyclodextrin metal-organic frameworks. J Microencapsulation. 2018;35(3):249–58.

    Article  CAS  PubMed  Google Scholar 

  7. Li Z, Wang M, Wang F, Gu Z, Du G, Wu J, et al. Gamma-cyclodextrin: a review on enzymatic production and applications. Appl Microbiol Biotechnol. 2007;77(2):245–55.

    Article  CAS  PubMed  Google Scholar 

  8. Saokham P, Loftsson T. γ-Cyclodextrin. Int J Pharmaceut. 2017;516(1):278–92.

    Article  CAS  Google Scholar 

  9. Xu L, Xing CY, Ke D, Chen L, Qiu ZJ, Zeng SL, et al. Amino-functionalized β-Cyclodextrin to construct green metal-organic framework materials for CO2 capture. ACS Appl Mater Interf. 2020;12(2):3032–41.

    Article  CAS  Google Scholar 

  10. Hu Z, Shao M, Zhang B, Fu X, Huang Q. Enhanced stability and controlled release of menthol using a β-cyclodextrin metal-organic framework. Food Chem. 2022;374:131760.

    Article  CAS  PubMed  Google Scholar 

  11. Rajkumar T, Kukkar D, Kim KH, Sohn JR, Deep A. Cyclodextrin-metal-organic framework (CD-MOF): from synthesis to applications. J Indust Eng Chem. 2019;72:50–66.

    Article  CAS  Google Scholar 

  12. Shen M, Liu D, Ding T. Cyclodextrin-metal-organic frameworks (CD-MOFs): main aspects and perspectives in food applications. Curr Opin in Food Sci, 2021;41:8–15.

  13. Lu H, Yang X, Li S, Zhang Y, Sha J, Li C, et al. Study on a new cyclodextrin based metal-organic framework with chiral helices. Inorgan Chem Commun. 2015;61:48–52.

    Article  CAS  Google Scholar 

  14. Liu J, Bao TY, Yang XY, Zhu PP, Wu LH, Sha JQ, et al. Controllable porosity conversion of metal-organic frameworks composed of natural ingredients for drug delivery. Chem Commun. 2017;53(55):7804–7.

    Article  CAS  Google Scholar 

  15. Sha JQ, Wu LH, Li SX, Yang XN, Zhang Y, Zhang QN, et al. Synthesis and structure of new carbohydrate metal-organic frameworks and inclusion complexes. J Molecul Struct. 2015;1101:14–20.

    Article  CAS  Google Scholar 

  16. Yang A, Liu H, Li Z, Li L, Li W, Liu K. Green synthesis of β-cyclodextrin metal-organic frameworks and the adsorption of quercetin and emodin. Polyhedron. 2019;159:116–26.

    Article  CAS  Google Scholar 

  17. Hu Z, Li S, Wang S, Zhang B, Huang Q. Encapsulation of menthol into cyclodextrin metal-organic frameworks: preparation, structure characterization and evaluation of complexing capacity. Food Chem. 2021;338:127839.

    Article  CAS  PubMed  Google Scholar 

  18. Xiong Y, Wu L, Guo T, Wang C, Wu W, Tang Y, et al. Crystal transformation of β-CD-MOF facilitates loading of dimercaptosuccinic acid. AAPS Pharm Sci Tech. 2019;20(6):224.

    Article  CAS  Google Scholar 

  19. He Y, Hou X, Liu Y, Feng N. Recent progress in the synthesis, structural diversity and emerging applications of cyclodextrin-based metal-organic frameworks. J Mater Chem B. 2019;7(37):5602–19.

    Article  CAS  PubMed  Google Scholar 

  20. Tanumihardjo SA. Vitamin A: biomarkers of nutrition for development. Ame J Clin Nutrit. 2011;94(2):658s–65s.

    Article  Google Scholar 

  21. N'Soukpoé-Kossi CN, Sedaghat-Herati R, Ragi C, Hotchandani S, Tajmir-Riahi HA. Retinol and retinoic acid bind human serum albumin: stability and structural features. Int J Biolog Macromolecul. 2007;40(5):484–90.

    Article  Google Scholar 

  22. Mohan MS, Jurat-Fuentes JL, Harte F. Binding of vitamin A by casein micelles in commercial skim milk. J Dairy Sci. 2013;96(2):790–8.

    Article  CAS  PubMed  Google Scholar 

  23. Ghouchi-Eskandar N, Simovic S, Prestidge CA. Solid-state nanoparticle coated emulsions for encapsulation and improving the chemical stability of all-trans-retinol. Int J Pharmaceut. 2012;423(2):384–91.

    Article  CAS  Google Scholar 

  24. Gonnet M, Lethuaut L, Boury F. New trends in encapsulation of liposoluble vitamins. J Control Release: Official J Control Release Soc. 2010;146(3):276–90.

    Article  CAS  Google Scholar 

  25. Vilanova N, Solans C. Vitamin A palmitate-β-cyclodextrin inclusion complexes: characterization, protection and emulsification properties. Food Chem. 2015;175:529–35.

    Article  CAS  PubMed  Google Scholar 

  26. Gonçalves A, Estevinho BN, Rocha F. Microencapsulation of vitamin A: a review. Trends Food Sci Technol. 2016;51:76–87.

    Article  Google Scholar 

  27. Ro J, Kim Y, Kim H, Park K, Lee KE, Khadka P, et al. Pectin Micro- and Nano-capsules of retinyl palmitate as cosmeceutical carriers for stabilized skin transport. Korean J Physio Pharmacol: Official J Korean Physiolog Soc Korean Soc Pharmacol. 2015;19(1):59–64.

    Article  CAS  Google Scholar 

  28. Moccand C, Martin F, Martiel I, Gancel C, Michel M, Fries L, et al. Vitamin A degradation in triglycerides varying by their saturation levels. Food Research Int. 2016;88:3–9.

    Article  CAS  Google Scholar 

  29. Bourassa P, N’soukpoé-Kossi CN, Tajmir-Riahi HA. Binding of vitamin A with milk α- and β-caseins. Food Chem. 2013;138(1):444–53.

  30. Pignitter M, Dumhart B, Gartner S, Jirsa F, Steiger G, Kraemer K, et al. Vitamin A is rapidly degraded in retinyl palmitate-fortified soybean oil stored under household conditions. J Agricult Food Chem. 2014;62(30):7559–66.

    Article  CAS  Google Scholar 

  31. Hemery YM, Fontan L, Moench-Pfanner R, Laillou A, Berger J, Renaud C, et al. Influence of light exposure and oxidative status on the stability of vitamins A and D3 during the storage of fortified soybean oil. Food Chem. 2015;184:90–8.

    Article  CAS  PubMed  Google Scholar 

  32. Gangurde AB, Amin PD. Microencapsulation by spray drying of vitamin A palmitate from oil to powder and its application in topical delivery system. J Encapsul Adsorpt Sci. 2017;07(1):10–39.

    CAS  Google Scholar 

  33. Xu M, Watson J. Microencapsulated vitamin A palmitate degradation mechanism study to improve the product stability. J Agricult Food Chem. 2021;69(51):15681–90.

    Article  CAS  Google Scholar 

  34. Han Y, Liu W, Huang J, Qiu S, Zhong H, Liu D, et al. Cyclodextrin-based metal-organic frameworks (CD-MOFs) in pharmaceutics and biomedicine. Pharmaceutics. 2018;10(4):271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Omar TA, Oka S, Muzzio FJ, Glasser BJ. Manufacturing of pharmaceuticals by impregnation of an active pharmaceutical ingredient onto a mesoporous carrier: impact of solvent and loading. J Pharmaceut Innov. 2019;14(3):194–205.

    Article  Google Scholar 

  36. Zheng H, Zhang Y, Liu L, Wei W, Peng G, Nystroem AM, et al. One-pot synthesis of metal-organic frameworks with encapsulated target molecules and their applications for controlled drug delivery. J Ame Chem Soc. 2016;138(3):962–8.

    Article  CAS  Google Scholar 

  37. Nawrocki J, Prochowicz D, Wisniewski A, Justyniak I, Gos P, Lewinski J. Development of an SBU-Based mechanochemical approach for drug-loaded MOFs. Europ J Inorg Chem. 2020;2020(10):796–800.

    Article  CAS  Google Scholar 

  38. Walton KS, Snurr RQ. Applicability of the BET method for determining surface areas of microporous metal-organic frameworks. J Ame Chem Soc. 2007;129(27):8552–6.

    Article  CAS  Google Scholar 

  39. Chen J, Guo T, Ren X, Yang T, Zhang K, Guo Y, et al. Efficient capture and stabilization of iodine via gas-solid reaction using cyclodextrin metal-organic frameworks. Carbohyd Polym. 2022;291:119507.

  40. Phillips JC, Hardy DJ, Maia JDC, Stone JE, Ribeiro JV, Bernardi RC, et al. Scalable molecular dynamics on CPU and GPU architectures with NAMD. J Chem Phys. 2020;153(4):044130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors are thankful for the financial support from the National Natural Science Foundation of China (82273863). Thanks go to the staff from BL01B beamline of the National Facility for Protein Science in Shanghai (NFPS) at Shanghai Synchrotron Radiation Facility for assistance during data collection.

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Authors and Affiliations

  1. Anhui University of Chinese Medicine, Hefei, 230012, China

    Ying Zhang, Huajie Zhu, Xiangyu Zhao, Weidong Chen, Jiwen Zhang & Li Wu

  2. Key Laboratory of Molecular Pharmacology and Drug Evaluation, School of Pharmacy, Ministry of Education, Yantai University, Yantai, 264005, China

    Jiwen Zhang & Li Wu

  3. Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201210, China

    Jiacai Chen, Zaiyong Zhang, Wuzhen Ma, Manli Wang, Caifen Wang, Jiwen Zhang, Tao Guo & Li Wu

  4. Yangtze Delta Drug Advanced Research Institute, Nantong, 226133, China

    Ying Zhang, Huajie Zhu, Wuzhen Ma, Xiangyu Zhao, Jiwen Zhang & Li Wu

  5. NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients, National Institutes for Food and Drug Control, Beijing, 100050, China

    Jiwen Zhang & Li Wu

  6. Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, 330004, China

    Abid Naeem

Authors
  1. Ying Zhang
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Contributions

Ying Zhang carried out most experiments under the guidance of Jiwen Zhang, Li Wu, Tao Guo, and Weidong Chen. Zaiyong Zhang and Jiacai Chen helped to accomplish the cultivation and optimization of the single crystal. Caifen Wang, Huajie Zhu, and Xiangyu Zhao helped with the stability experiment and quantification. Wuzhen Ma and Manli Wang assisted with the review. Abid Naeem helped to improve the English style and rectify any grammatical mistakes. All authors discussed the results and commented on the manuscript.

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Correspondence to Jiwen Zhang, Tao Guo or Li Wu.

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Zhang, Y., Chen, J., Zhang, Z. et al. Solvent-Free Loading of Vitamin A Palmitate into β-Cyclodextrin Metal-Organic Frameworks for Stability Enhancement. AAPS PharmSciTech 24, 136 (2023). https://doi.org/10.1208/s12249-023-02596-7

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