{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T10:15:28Z","timestamp":1783160128759,"version":"3.54.6"},"reference-count":36,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T00:00:00Z","timestamp":1600560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This work demonstrates synthetic strategies for the incorporation of a synthesized pyrimidine glucagon-like peptide-1 (GLP-1) agonist into alginate-coated ZIF-8. The prepared pyrimidine GLP-1 agonist used for the treatment of diabetes type II, was trapped inside polymer coated ZIF-8. The encapsulation of the GLP-1 agonist was confirmed by UV-visible and FT-IR spectroscopies. Furthermore, the release kinetics of GLP-1 agonist drug from alginate-coated ZIF-8 were investigated in phosphate-buffered saline at 37 \u00b0C at pH 8 and 1.5. The alginate-coated ZIF-8 exhibited much faster drug release at basic pH than at pH 1.5, indicating the potential of the alginate-coated ZIF-8 system to overcome the fast degradation at acidic pH of the stomach and improve the drug\u2019s activity. This study may open the way for the synthesis of new metal organic frameworks (MOFs) to enhance drug delivery systems.<\/jats:p>","DOI":"10.3390\/molecules25184313","type":"journal-article","created":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T21:20:28Z","timestamp":1600636828000},"page":"4313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Controlled Release of Pyrimidine Compound Using Polymeric Coated ZIF-8 Metal-Organic Framework as Glucagon-Like Peptide-1 Receptor Agonist Carrier"],"prefix":"10.3390","volume":"25","author":[{"given":"Shaikha S.","family":"AlNeyadi","sequence":"first","affiliation":[{"name":"Department of Chemistry, College of Science, UAE University, Al-Ain P.O. Box 15551, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2141-3210","authenticated-orcid":false,"given":"Naheed","family":"Amir","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Health and Science, UAE University, Al-Ain P.O. Box 17666, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2240-8037","authenticated-orcid":false,"given":"Mohammad A.","family":"Ghattas","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Al Ain University, Abu Dhabi P.O. Box 112612, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2788-0875","authenticated-orcid":false,"given":"Noor","family":"Atatreh","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Al Ain University, Abu Dhabi P.O. Box 112612, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaikha S.","family":"Alketbi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, UAE University, Al-Ain P.O. Box 15551, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruba Al","family":"Ajeil","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, UAE University, Al-Ain P.O. Box 15551, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9289-5301","authenticated-orcid":false,"given":"Abdu","family":"Adem","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Health and Science, UAE University, Al-Ain P.O. Box 17666, UAE"},{"name":"Department of Pharmacology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi P.O. Box 127788, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s12272-013-0025-6","article-title":"Where are we now in diabetic research?","volume":"36","author":"Kwak","year":"2013","journal-title":"Arch. Pharmacal. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00592-009-0134-3","article-title":"Is the current therapeutic armamentarium in diabetes enough to control the epidemic and its consequences? What are the current shortcomings?","volume":"46","author":"Giugliano","year":"2009","journal-title":"Acta Diabetol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1463-1326.2012.01663.x","article-title":"GLP-1 receptor activated insulin secretion from pancreatic \u03b2-cells: Mechanism and glucose dependence","volume":"15","author":"Meloni","year":"2012","journal-title":"Diabetes Obes. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1053\/j.gastro.2007.03.054","article-title":"Biology of Incretins: GLP-1 and GIP","volume":"132","author":"Baggio","year":"2007","journal-title":"Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/sj.ijo.0801627","article-title":"The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity","volume":"25","author":"Flint","year":"2001","journal-title":"Int. J. Obes."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/379069a0","article-title":"A role for glucagon-like peptide-1 in the central regulation of feeding","volume":"379","author":"Turton","year":"1996","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.2337\/diab.44.9.1126","article-title":"Both Subcutaneously and Intravenously Administered Glucagon-Like Peptide I Are Rapidly Degraded from the NH2-Terminus in Type II Diabetic Patients and in Healthy Subjects","volume":"44","author":"Deacon","year":"1995","journal-title":"Diabetes"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1586\/eem.10.20","article-title":"Liraglutide, the once-daily human GLP-1 analog, in the treatment of Type 2 diabetes","volume":"5","author":"Hribal","year":"2010","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1073\/pnas.0610679104","article-title":"Nonpeptidic glucagon-like peptide 1 receptor agonists: A magic bullet for diabetes?","volume":"104","author":"Murphy","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13408","DOI":"10.1039\/C5CC05136C","article-title":"Facile synthesis of multiple enzyme-containing metal\u2013organic frameworks in a biomolecule-friendly environment","volume":"51","author":"Wu","year":"2015","journal-title":"Chem. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1021\/jacs.5b11720","article-title":"One-pot Synthesis of Metal\u2013Organic Frameworks with Encapsulated Target Molecules and Their Applications for Controlled Drug Delivery","volume":"138","author":"Zheng","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.apsb.2019.08.003","article-title":"Recent progress in drug delivery","volume":"9","author":"Li","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3807","DOI":"10.1002\/smll.201500155","article-title":"Zn2+-Triggered Drug Release from Biocompatible Zirconium MOFs Equipped with Supramolecular Gates","volume":"11","author":"Tan","year":"2015","journal-title":"Small"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1021\/nn406590q","article-title":"Optimized Metal\u2013Organic-Framework Nanospheres for Drug Delivery: Evaluation of Small-Molecule Encapsulation","volume":"8","author":"Zhuang","year":"2014","journal-title":"ACS Nano"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10186","DOI":"10.1073\/pnas.0602439103","article-title":"Exceptional chemical and thermal stability of zeolitic imidazolate frameworks","volume":"103","author":"Park","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","first-page":"201","article-title":"Crystal and Molecular Structure Analysis of 2-Methylimidazole","volume":"40","author":"Nowak","year":"2009","journal-title":"J. Chem. Crystallogr."},{"key":"ref_17","unstructured":"Mancini, M.M., Nieto, J.C.D.C., and Amat, E.D.R. (2001). Novel Thiazolidinedione Derivatives as Antidiabetic Agents, VITA INVEST SA. (Patent no. WO 2001036416 A)."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11340","DOI":"10.1074\/jbc.M708740200","article-title":"Crystal Structure of the Ligand-bound Glucagon-like Peptide-1 Receptor Extracellular Domain","volume":"283","author":"Runge","year":"2008","journal-title":"J. Boil. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.2337\/db10-0689","article-title":"Novel Small Molecule Glucagon-Like Peptide-1 Receptor Agonist Stimulates Insulin Secretion in Rodents and From Human Islets","volume":"59","author":"Sloop","year":"2010","journal-title":"Diabetes"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s00894-008-0372-2","article-title":"Molecular modeling of the three-dimensional structure of GLP-1R and its interactions with several agonists","volume":"15","author":"Lin","year":"2008","journal-title":"J. Mol. Model."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Undheim, K., and Benneche, T. (1996). Pyrimidines and their Benzo Derivatives. Comprehensive Heterocyclic Chemistry II, Elsevier BV.","DOI":"10.1016\/B978-008096518-5.00118-0"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1039\/c0cc05002d","article-title":"Rapid synthesis of zeolitic imidazolate framework-8 (ZIF-8) nanocrystals in an aqueous system","volume":"47","author":"Pan","year":"2011","journal-title":"Chem. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4493","DOI":"10.1039\/C3CE42485E","article-title":"Controlling ZIF-8 nano- and microcrystal formation and reactivity through zinc salt variations","volume":"16","author":"Schejn","year":"2014","journal-title":"Cryst. Eng. Comm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.matdes.2017.03.002","article-title":"Microfluidic reactors for the size-controlled synthesis of ZIF-8 crystals in aqueous phase","volume":"122","author":"Kolmykov","year":"2017","journal-title":"Mater. Des."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1021\/cm900166h","article-title":"Rapid Room-Temperature Synthesis and Characterization of Nanocrystals of a Prototypical Zeolitic Imidazolate Framework","volume":"21","author":"Cravillon","year":"2009","journal-title":"Chem. Mater."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.memsci.2010.06.017","article-title":"Molecular sieving realized with ZIF-8\/Matrimid\u00ae\u00ae mixed-matrix membranes","volume":"361","author":"Ordonez","year":"2010","journal-title":"J. Membr. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12694","DOI":"10.1039\/c1cc15525c","article-title":"In situ high pressure study of ZIF-8 by FTIR spectroscopy","volume":"47","author":"Hu","year":"2011","journal-title":"Chem. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12246","DOI":"10.1039\/c2jm31541f","article-title":"A novel method to improve the gas storage capacity of ZIF-8","volume":"22","author":"Mu","year":"2012","journal-title":"J. Mater. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1039\/c2ra00657j","article-title":"Silica nanocubes with a hierarchically porous structure","volume":"2","author":"Kong","year":"2012","journal-title":"RSC Adv."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"(2012). Graphical contents list. Tetrahedron Lett., 53, 2925\u20132935.","DOI":"10.1016\/S0040-4039(12)00752-6"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"J. Comput. Mol. Des."},{"key":"ref_32","unstructured":"(2007, November 10). Schordinger Software, Version 8.0. Available online: http:\/\/www.schrodinger.com\/."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ejmech.2012.07.036","article-title":"Synthesis, characterization, screening and docking analysis of 4-anilinoquinazoline derivatives as tyrosine kinase inhibitors","volume":"61","author":"Lu","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1016\/S0040-4039(01)00124-1","article-title":"A novel ZrO2\u2013SO42\u2212 supported palladium catalyst for syntheses of disubstituted ureas from amines by oxidative carbonylation","volume":"42","author":"Shi","year":"2001","journal-title":"Tetrahedron Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1016\/j.bmc.2011.03.032","article-title":"Metabolic stability of 6,7-dialkoxy-4-(2-, 3- and 4-[18F]fluoroanilino)quinazolines, potential EGFR imaging probes","volume":"19","author":"Vasdev","year":"2011","journal-title":"Bioorganic Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra Precision Glide: Docking and Scoring Incorporating a Model of Hydrophobic Enclosure for Protein\u2212Ligand Complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/18\/4313\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:11:48Z","timestamp":1760177508000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/18\/4313"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,20]]},"references-count":36,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["molecules25184313"],"URL":"https:\/\/doi.org\/10.3390\/molecules25184313","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,20]]}}}