Development and Characterization of Zinc-Based Metal–Organic Frameworks for Sustained Delivery of Clonidine Hydrochloride
DOI:
https://doi.org/10.64261/6v9kt186Keywords:
Clonidine Hydrochloride, Drug Delivery, Metal-Organic Frameworks, Sustained Release, Zinc-Based MOFs.Abstract
The present study focuses on the development and characterization of zinc-based metal–organic frameworks (MOFs) for the sustained oral delivery of clonidine hydrochloride, a centrally acting antihypertensive drug with a short biological half-life and dose-related adverse effects. Zinc acetate was employed as the metal source, while fumaric acid and succinic acid were investigated as organic linkers to evaluate their influence on framework formation, drug entrapment, and release behavior. MOFs were synthesized using precipitation and solvent evaporation techniques, and drug loading was achieved through in-process and post-synthetic methods. Eight formulations (C1–C8) were prepared and screened based on percentage yield and entrapment efficiency. Fumaric acid-based MOFs (C1–C4) exhibited poor yield and low drug entrapment, leading to their exclusion from further optimization. In contrast, succinic acid-based MOFs (C5–C8) demonstrated significantly improved performance, with formulation C7 showing the highest entrapment efficiency (68.00 ± 0.08%) and percentage yield (69.33 ± 0.77%). The optimized formulation was subjected to detailed physicochemical characterization using powder X-ray diffraction, scanning electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and particle size analysis, confirming successful drug encapsulation, structural integrity, and nanoscale particle size. In vitro drug release studies revealed a sustained release of clonidine hydrochloride over 8 hours, following diffusion-controlled kinetics best described by the Korsmeyer–Peppas model. Accelerated stability studies conducted according to ICH guidelines demonstrated good physicochemical stability and acceptable shelf-life characteristics. Overall, the findings suggest that succinic acid-based zinc MOFs represent a promising platform for sustained oral delivery of clonidine hydrochloride, with potential to improve therapeutic efficacy and patient compliance in hypertension management.
References
1. Goorani S, Zangene S, Imig JD. Hypertension: A Continuing Public Healthcare Issue. Int J Mol Sci 2025, Vol 26, Page 123 [Internet]. 2024 [cited 2025 Jun 29];26:123. Available from: https://www.mdpi.com/1422-0067/26/1/123/htm DOI: https://doi.org/10.3390/ijms26010123
2. Larkin KT, Frazier A, Cavanagh CE. Hypertension. Encycl Ment Heal Third Ed Vol 1-3 [Internet]. 2023 [cited 2025 Jun 29];2:208–16. Available from: https://www.sciencedirect.com/science/article/abs/pii/B9780323914970000382?via%3Dihub DOI: https://doi.org/10.1016/B978-0-323-91497-0.00038-2
3. Mirza M, Hameda Nishath S, Umaira Saeed F. The Silent Storm: Understanding Hypertension. Int J Innov Sci Res Technol. 2024;3405–15. DOI: https://doi.org/10.38124/ijisrt/IJISRT24APR1387
4. Kreutz R, Abdel-Hady Algharably E. Novel Drugs in the Treatment of Hypertension. 2016 [cited 2025 Jun 29];157–78. Available from: https://link.springer.com/chapter/10.1007/978-3-319-34141-5_10 DOI: https://doi.org/10.1007/978-3-319-34141-5_10
5. Marinov P, Georgiev K, Georgieva M. Some aspects of the modern antihypertensive drug therapy and most common side effects. Scr Sci Pharm [Internet]. 2015 [cited 2025 Jun 29];2:7–14. Available from: https://journals.mu-varna.bg/index.php/ssp/article/view/1045 DOI: https://doi.org/10.14748/ssp.v1i1.1045
6. Hall C, Choi H. Side effects of antihypertensive drugs. Side Eff Drugs Annu [Internet]. 2023 [cited 2025 Jun 29];45:199–208. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0378608023000041?via%3Dihub DOI: https://doi.org/10.1016/bs.seda.2023.07.004
7. He Z, Chen J, Zhang J, Yang DD, Li CZ, Zhao B, et al. Clonidine ameliorates cerebral ischemia-reperfusion injury by modulating the GluN3 subunits of NMDA receptor. 2022 [cited 2025 Jun 29]; Available from: https://www.researchsquare.com DOI: https://doi.org/10.21203/rs.3.rs-1501356/v1
8. Gold MS, Blum K. Clonidine. Oxford Handb Opioids Opioid Use Disord [Internet]. 2023 [cited 2025 Jun 2];543–70. Available from: https://academic.oup.com/edited-volume/45895/chapter/425900819 DOI: https://doi.org/10.1093/oxfordhb/9780197618431.013.20
9. Gomez RS, Fernandes ML. Clonidine: Features and applications. Treat Mech Advers React Anesth Analg [Internet]. 2022 [cited 2025 Jun 29];81–8. Available from: https://www.sciencedirect.com/science/article/abs/pii/B9780128202371000090?via%3Dihub DOI: https://doi.org/10.1016/B978-0-12-820237-1.00009-0
10. Patil S, Tayebjee M, Nadar SK. Other antihypertensive agents. Case Stud Clin Psychol Sci Bridg Gap from Sci to Pract [Internet]. 2022 [cited 2025 Jun 2];1–7. Available from: https://academic.oup.com/book/44582/chapter/377358571
11. Horcajada P, Gref R, Baati T, Allan PK, Maurin G, Couvreur P, et al. Metal-organic frameworks in biomedicine. Chem Rev. 2012;112:1232–68. DOI: https://doi.org/10.1021/cr200256v
12. Fan X, Liu F, Zheng G. Metal-Organic Frameworks for Drug Delivery. Highlights Sci Eng Technol [Internet]. 2022 [cited 2025 May 16];6:165–71. Available from: https://drpress.org/ojs/index.php/HSET/article/view/958 DOI: https://doi.org/10.54097/hset.v6i.958
13. Sun Y, Zheng L, Yang Y, Qian X, Fu T, Li X, et al. Metal–Organic Framework Nanocarriers for Drug Delivery in Biomedical Applications. Nano-Micro Lett [Internet]. 2020 [cited 2025 Jun 13];12. Available from: https://pubmed.ncbi.nlm.nih.gov/34138099/ DOI: https://doi.org/10.1007/s40820-020-00423-3
14. Kundu S, Swaroop AK, Selvaraj J. Metal-Organic Framework in Pharmaceutical Drug Delivery. Curr Top Med Chem [Internet]. 2023 [cited 2025 May 16];23:1155–70. Available from: https://www.eurekaselect.com/article/129237 DOI: https://doi.org/10.2174/1568026623666230202122519
15. Ye X, Xiong M, Yuan K, Liu W, Cai X, Yuan Y, et al. Synthesis and Characterization of a Novel Zinc-Based Metal-Organic Framework Containing Benzoic Acid: A Low-Toxicity Carrier for Drug Delivery. Iran J Pharm Res 2023 221 [Internet]. 2023 [cited 2025 Jun 29];22. Available from: https://brieflands.com/articles/ijpr-136238 DOI: https://doi.org/10.5812/ijpr-136238
16. Khafaga DSR, El-Morsy MT, Faried H, Diab AH, Shehab S, Saleh AM, et al. Metal–organic frameworks in drug delivery: engineering versatile platforms for therapeutic applications. RSC Adv [Internet]. 2024 [cited 2025 May 16];14:30201–29. Available from: https://pubs.rsc.org/en/content/articlehtml/2024/ra/d4ra04441j DOI: https://doi.org/10.1039/D4RA04441J
17. Rabiee N. Sustainable metal-organic frameworks (MOFs) for drug delivery systems. Mater Today Commun [Internet]. 2023 [cited 2025 Jun 29];35:106244. Available from: https://www.sciencedirect.com/science/article/abs/pii/S2352492823009352?via%3Dihub DOI: https://doi.org/10.1016/j.mtcomm.2023.106244
18. Le C, Nguyen Thi Lan N, Do Thi Hong D, Nguyen Thanh T, Nguyen Le Hong V. Update on the drug treatment of hypertension: perspectives in clinical pharmacology. J Med Pharm. 2022;13–20. DOI: https://doi.org/10.34071/jmp.2022.7.2
19. Getachew N, Chebude Y, Diaz I, Sanchez-Sanchez M. Room temperature synthesis of metal organic framework MOF-2. J Porous Mater. 2014;21:769–73. DOI: https://doi.org/10.1007/s10934-014-9823-6
20. Cretu C, Nicola R, Marinescu SA, Picioruș EM, Suba M, Duda-Seiman C, et al. Performance of Zr-Based Metal–Organic Framework Materials as In Vitro Systems for the Oral Delivery of Captopril and Ibuprofen. Int J Mol Sci. 2023;24. DOI: https://doi.org/10.3390/ijms241813887
21. Zheng H, Zhang Y, Liu L, Wan W, Guo P, Nyström AM, et al. One-pot Synthesis of Metal-Organic Frameworks with Encapsulated Target Molecules and Their Applications for Controlled Drug Delivery. J Am Chem Soc. 2016;138:962–8. DOI: https://doi.org/10.1021/jacs.5b11720
22. Lai Q, Yao L, Gao Z, Liu S, Wang H, Lu S, et al. End-to-End Crystal Structure Prediction from Powder X-Ray Diffraction. Adv Sci [Internet]. 2024 [cited 2025 Jun 23];12:2410722. Available from: http://arxiv.org/abs/2401.03862 DOI: https://doi.org/10.1002/advs.202410722
23. Sun W, Xu Y, Zhou Y, Zeng Z, Wang L, Ouyang J. Topographic Scanning Electronic Microscopy Reveals the 3D Surface Structure of Materials. Adv Funct Mater [Internet]. 2025 [cited 2025 Jun 23];35:2420372. Available from: /doi/pdf/10.1002/adfm.202420372 DOI: https://doi.org/10.1002/adfm.202420372
24. Linder-Patton OM, Bloch WM, Coghlan CJ, Sumida K, Kitagawa S, Furukawa S, et al. Particle size effects in the kinetic trapping of a structurally-locked form of a flexible MOF. CrystEngComm [Internet]. 2016 [cited 2025 Jun 23];18:4172–9. Available from: https://pubs.rsc.org/en/content/articlehtml/2016/ce/c6ce00082g DOI: https://doi.org/10.1039/C6CE00082G
25. Singh A, Sharma A, K. Verma R, L. Chopade R, P. Pandit P, Nagar V, et al. Heavy Metal Contamination of Water and Their Toxic Effect on Living Organisms. Toxic Environ Pollut. 2022; DOI: https://doi.org/10.5772/intechopen.105075
26. Baumgartner B, Ikigaki K, Okada K, Takahashi M. Infrared crystallography for framework and linker orientation in metal–organic framework films. Chem Sci [Internet]. 2021 [cited 2025 Jun 23];12:9298–308. Available from: https://pubs.rsc.org/en/content/articlehtml/2021/sc/d1sc02370e DOI: https://doi.org/10.1039/D1SC02370E
27. Mora-Castaño G, Millán-Jiménez M, Caraballo I. Hydrophilic High Drug-Loaded 3D Printed Gastroretentive System with Robust Release Kinetics. Pharmaceutics [Internet]. 2023 [cited 2025 Jun 23];15. Available from: https://pubmed.ncbi.nlm.nih.gov/36986703/ DOI: https://doi.org/10.3390/pharmaceutics15030842
28. INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS Q1A(R2). 2003;
29. Diaz DA, Colgan ST, Langer CS, Bandi NT, Likar MD, Van Alstine L. Dissolution Similarity Requirements: How Similar or Dissimilar Are the Global Regulatory Expectations? AAPS J [Internet]. 2016 [cited 2025 Jun 23];18:15–22. Available from: https://pubmed.ncbi.nlm.nih.gov/26428517/ DOI: https://doi.org/10.1208/s12248-015-9830-9
Downloads
Published
Issue
Section
Categories
License
Copyright (c) 2026 Pan-African Journal of Health and Psychological Sciences
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
All articles published in the Pan-African Journal of Health and Psychological Sciences (PAJHPS) are open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0).
Under this license:
-
Authors retain copyright and grant the journal the right of first publication.
-
The work may be shared, copied, redistributed, and adapted for any purpose, even commercially.
-
Appropriate credit must be given to the original author(s) and the journal, along with a link to the license.
-
Users must indicate if changes were made.
-
There are no restrictions on reuse, provided the original work is properly cited.
Citation:
Authors and users must cite the original work in the following manner:
Author(s). (Year). Title of the article. Pan-African Journal of Health and Psychological Sciences, Volume(Issue), page range. https://doi.org/xx.xxxx/pajhps.vXnY.xxx
Copyright Statement:
Authors grant PAJHPS a non-exclusive license to publish the work and identify itself as the original publisher. Authors may enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version (e.g., post it to a repository or publish it in a book), with acknowledgment of its initial publication in this journal.
