Research Article
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Year 2023, Volume: 41 Issue: 6, 1106 - 1114, 29.12.2023

Abstract

References

  • REFERENCES
  • [1] Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet 2017;389:2239–2251. [CrossRef]
  • [2] International Diabetes Federation. IDF Diabetes Atlas. 9th ed. Diabetes Atlas http://www.diabetesatlas.org/ 2019.
  • [3] Turner RC, Cull CA, Frighi V, Holman RR, UK Prospective Diabetes Study (UKPDS) Group. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA 1999;281:2005–2012. [CrossRef]
  • [4] Stein SA, Lamos EM, Davis SN. A review of the efficacy and safety of oral antidiabetic drugs. Expert Opin Drug Saf 2013;12:153–175. [CrossRef]
  • [5] Foretz M, Guigas B, Viollet B. Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus. Nat Rev Endocrinol 2019;15:569–589. [CrossRef]
  • [6] Krentz AJ, Bailey CJ. Oral antidiabetic agents. Drugs 2005;65:385–411. [CrossRef]
  • [7] Nasri H, Rafieian-Kopaei M. Metformin: current knowledge. J Res Med Sci 2014;19:658. [CrossRef]
  • [8] Cesur S, Cam ME, Sayın FS, Su S, Harker A, Edirisinghe M, Gunduz O. Metformin-loaded polymer-based microbubbles/nanoparticles generated for the treatment of type 2 diabetes mellitus. Langmuir 2022;38:50405051. [CrossRef]
  • [9] Berman B. 3-D printing: The new industrial revolution. Bus Horiz 2012;55:155–162. [CrossRef]
  • [10] Calori IR, Braga G, de Jesus PDCC, Bi H, Tedesco AC. Polymer scaffolds as drug delivery systems. Eur Polym J 2020;129:109621. [CrossRef]
  • [11] Vaezi M, Zhong G, Kalami H, Yang S. Extrusion-based 3D printing technologies for 3D scaffold engineering. In Functional 3D Tissue Engineering Scaffolds. Cambridge: Woodhead Publishing; 2018. p. 235–254. [CrossRef]
  • [12] Annaji M, Ramesh S, Poudel I, Govindarajulu M, Arnold RD, Dhanasekaran M, et al. Application of extrusion-based 3d printed dosage forms in the treatment of chronic diseases. J Pharm Sci 2020;109:35513568. [CrossRef]
  • [13] Palo M, Holländer J, Suominen J, Yliruusi J, Sandler N. 3D printed drug delivery devices: perspectives and technical challenges. Expert Rev Med Dev 2017;14:685–696. [CrossRef]
  • [14] Nikolova MP, Chavali MS. Recent advances in biomaterials for 3D scaffolds: A review. Bioact Mater 2019;4:271–292. [CrossRef]
  • [15] Wang Y, Wang X, Shi J, Zhu R, Zhang J, Zhang Z, et al. A biomimetic silk fibroin/sodium alginate composite scaffold for soft tissue engineering. Sci Rep 2016;6:1–13. [CrossRef]
  • [16] Shen W, Hsieh YL. Biocompatible sodium alginate fibers by aqueous processing and physical crosslinking. Carbohydr Polym 2014;102:893–900. [CrossRef]
  • [17] Wu J, Wei W, Wang LY, Su ZG, Ma GH. A thermosensitive hydrogel based on quaternized chitosan and poly (ethylene glycol) for nasal drug delivery system. Biomaterials 2007;28:2220–2232. [CrossRef]
  • [18] Chiu YC, Larson JC, Isom Jr A, Brey EM. Generation of porous poly (ethylene glycol) hydrogels by salt leaching. Tissue Eng Part C Methods 2010;16:905–912. [CrossRef]
  • [19] Chen BY, Jing X, Mi HY, Zhao H, Zhang WH, Peng XF, et al. Fabrication of polylactic acid/polyethylene glycol (PLA/PEG) porous scaffold by supercritical CO 2 foaming and particle leaching. Polym Eng Sci 2015;55:1339–1348. [CrossRef]
  • [20] You F, Wu X, Chen X. 3D printing of porous alginate/gelatin hydrogel scaffolds and their mechanical property characterization. Int J Polym Mater Polym Biomater 2017;66:299–306. [CrossRef]
  • [21] Cesur S, Cam ME, Sayin FS, Su S, Gunduz O. Controlled Release of Metformin Loaded Polyvinyl Alcohol (PVA) Microbubble/Nanoparticles Using Microfluidic Device for the Treatment of Type 2 Diabetes Mellitus. In IWBBIO 2020, May. pp. 185–193. [CrossRef]
  • [22] Pramono E, Utomo SB, Wulandari V, Clegg F. FTIR studies on the effect of concentration of polyethylene glycol on polimerization of Shellac. J Physics Conf Ser 2016;776: 012053. [CrossRef]
  • [23] Shameli K, Bin Ahmad M, Jazayeri SD, Sedaghat S, Shabanzadeh P, Jahangirian H, et al. Synthesis and characterization of polyethylene glycol mediated silver nanoparticles by the green method. Int J Mol Sci 2012;13:6639–6650. [CrossRef]
  • [24] Cesur S, Oktar FN, Ekren N, Kilic O, Alkaya DB, Seyhan SA et al. Preparation and characterization of electrospun polylactic acid/sodium alginate/orange oyster shell composite nanofiber for biomedical application. J Aust Ceram Soci 2020;56:533–543. [CrossRef]
  • [25] Murphy CM, O'Brien FJ. Understanding the effect of mean pore size on cell activity in collagen-glycosaminoglycan scaffolds. Cell Adh Migr 2010;4:377–381. [CrossRef]
  • [26] Li J, Shen S, Kong F, Jiang T, Tang C, Yin C. Effects of pore size on in vitro and in vivo anticancer efficacies of mesoporous silica nanoparticles. RSC Adv 2018;8:24633–24640. [CrossRef]
  • [27] Sultan S, Mathew AP. 3D printed scaffolds with gradient porosity based on a cellulose nanocrystal hydrogel. Nanoscale 2018;10:4421–4431. [CrossRef]
  • [28] Choi DJ, Park SJ, Gu BK, Kim YJ, Chung S, Kim CH. Effect of the pore size in a 3D bioprinted gelatin scaffold on fibroblast proliferation. J Ind Eng Chem 2018;67:388–395. [CrossRef]
  • [29] Egan PF. Integrated design approaches for 3D printed tissue scaffolds: Review and outlook. Materials 2019;12:2355. [CrossRef]
  • [30] Hutmacher DW, Schantz JT, Lam CXF, Tan KC, Lim TC. State of the art and future directions of scaffold‐based bone engineering from a biomaterials perspective. J Tissue Eng Regen Med 2007;1:245–260. [CrossRef]
  • [31] Samadzadeh S, Mousazadeh H, Ghareghomi S, Dadashpour M, Babazadeh M, Zarghami N. In vitro anticancer efficacy of Metformin-loaded PLGA nanofibers towards the post-surgical therapy of lung cancer. J Drug Deliv Sci Technol 2021;61:102318. [CrossRef]
  • [32] Swamy TM, Ramaraj B, Lee JH. Sodium alginate and its blends with starch: thermal and morphological properties. J Appl Polym Sci 2008;109:4075–4081. [CrossRef]
  • [33] AlKhatib HS, Taha MO, Aiedeh KM, Bustanji Y, Sweileh B. Synthesis and in vitro evaluation of iron-crosslinked N-methyl and N-benzyl hydroxamated derivatives of alginic acid as controlled release carriers. Eur Polym J 2006;42:2464–2474. [CrossRef]
  • [34] Barkat K, Ahmad M, Minhas MU, Khalid I, Mahmood A. Understanding mechanical characteristics of pH-responsive PEG 4000-based polymeric network for colorectal carcinoma: its acute oral toxicity study. Polym Bull 2020;127. [CrossRef]
  • [35] Bouriche S, Alonso-García A, Cárceles-Rodríguez CM, Rezgui F, Fernández-Varón E. An in vivo pharmacokinetic study of metformin microparticles as an oral sustained release formulation in rabbits. BMC Vet Res 2021;17:111. [CrossRef]
  • [36] Shelke NB, James R, Laurencin CT, Kumbar SG. Polysaccharide biomaterials for drug delivery and regenerative engineering. Polym Adv Technol 2014;25:448–460. [CrossRef]
  • [37] Giyatmi G, Eka Poetri TA, Irianto H, Fransiska D, Agusman A. Effect of alginate and polyethylene glycol addition on physical and mechanical characteristics of k-carrageenan-based edible film. Squalen Bullet Marine Fisheries Postharvest Biotechnol 2020;15:4151. [CrossRef]
  • [38] Zhu J, Ye H, Deng D, Li J, Wu Y. Electrospun metformin-loaded polycaprolactone/chitosan nanofibrous membranes as promoting guided bone regeneration membranes: Preparation and characterization of fibers, drug release, and osteogenic activity in vitro. J Biomater Appl 2020;34:1282–1293. [CrossRef]
  • [39] Ebrahimi L, Farzin A, Ghasemi Y, Alizadeh A, Goodarzi A, Basiri A, Ai J. Metformin-loaded PCL/PVA fibrous scaffold preseeded with human endometrial stem cells for effective guided bone regeneration membranes. ACS Biomater Sci Eng 2020;7:222231. [CrossRef]
  • [40] Das MK, Senapati PC. Furosemide-loaded alginate microspheres prepared by ionic cross-linking technique: Morphology and release characteristics. Indian J Pharm Sci 2008;70:77. [CrossRef]
  • [41] Ozoude CH, Azubuike CP, Ologunagba MO, Tonuewa SS, Igwilo CI. Formulation and development of metformin-loaded microspheres using Khaya senegalensis (Meliaceae) gum as co- polymer. Future J Pharm Sci 2020;6:111. [CrossRef]
  • [42] Sriamornsak P, Nunthanid J, Cheewatanakornkool K, Manchun S. Effect of drug loading method on drug content and drug release from calcium pectinate gel beads. AAPS Pharm Sci Tech 2010;11:1315–1319. [CrossRef]

Controlled release of metformin-loaded SA/PEG scaffolds produced by 3d-printing technology

Year 2023, Volume: 41 Issue: 6, 1106 - 1114, 29.12.2023

Abstract

Type 2 diabetes mellitus (T2DM) is a long-term metabolic disease that is commonly character-ized by insulin deficiency or resistance, and prevalence has been increasing gradually all over the world. The aim of this study is to produce Metformin-loaded 3D printed scaffolds for an alter-native drug delivery application in the treatment of Type 2 DM with two different biopolymers. Sodium Alginate (SA)/Polyethylene glycol (PEG) scaffolds loaded with varying concentrations of Metformin (0.5 and 2 wt.%) were prepared by adding 9 wt.% of SA to 3 wt.% of PEG. The physical analyses of the solutions were examined after the production process, and as a result, no significant changes were observed in the viscosity, density, and surface tension of the solutions with the addition of Metformin. Morphological (SEM), molecular interaction (FTIR), thermal analysis (DSC), tensile strength analyses were done. SEM images and histograms showed that the desired pore structure was obtained in the scaffolds produced by the 3D printing method, and the average pore sizes were 236.14±18.999, 255.28±14.168, and 318.83±13.038 μm for SA/PEG, 0.5% and 2% Metformin-loaded scaffolds, respectively. A drug release test was performed by UV spectroscopy. Metformin from both 0.5% and 2% scaffolds showed a burst release in 30 minutes because of the high solubility of SA and PEG in water. More than 97% of the drug was released from both scaffolds. However, they displayed sustained release up to 24 hours. Therefore, Metformin-loaded 3D-printed scaffolds have promising potential for the treatment of T2DM as they are an alternative to the oral administration of the drug.

References

  • REFERENCES
  • [1] Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet 2017;389:2239–2251. [CrossRef]
  • [2] International Diabetes Federation. IDF Diabetes Atlas. 9th ed. Diabetes Atlas http://www.diabetesatlas.org/ 2019.
  • [3] Turner RC, Cull CA, Frighi V, Holman RR, UK Prospective Diabetes Study (UKPDS) Group. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA 1999;281:2005–2012. [CrossRef]
  • [4] Stein SA, Lamos EM, Davis SN. A review of the efficacy and safety of oral antidiabetic drugs. Expert Opin Drug Saf 2013;12:153–175. [CrossRef]
  • [5] Foretz M, Guigas B, Viollet B. Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus. Nat Rev Endocrinol 2019;15:569–589. [CrossRef]
  • [6] Krentz AJ, Bailey CJ. Oral antidiabetic agents. Drugs 2005;65:385–411. [CrossRef]
  • [7] Nasri H, Rafieian-Kopaei M. Metformin: current knowledge. J Res Med Sci 2014;19:658. [CrossRef]
  • [8] Cesur S, Cam ME, Sayın FS, Su S, Harker A, Edirisinghe M, Gunduz O. Metformin-loaded polymer-based microbubbles/nanoparticles generated for the treatment of type 2 diabetes mellitus. Langmuir 2022;38:50405051. [CrossRef]
  • [9] Berman B. 3-D printing: The new industrial revolution. Bus Horiz 2012;55:155–162. [CrossRef]
  • [10] Calori IR, Braga G, de Jesus PDCC, Bi H, Tedesco AC. Polymer scaffolds as drug delivery systems. Eur Polym J 2020;129:109621. [CrossRef]
  • [11] Vaezi M, Zhong G, Kalami H, Yang S. Extrusion-based 3D printing technologies for 3D scaffold engineering. In Functional 3D Tissue Engineering Scaffolds. Cambridge: Woodhead Publishing; 2018. p. 235–254. [CrossRef]
  • [12] Annaji M, Ramesh S, Poudel I, Govindarajulu M, Arnold RD, Dhanasekaran M, et al. Application of extrusion-based 3d printed dosage forms in the treatment of chronic diseases. J Pharm Sci 2020;109:35513568. [CrossRef]
  • [13] Palo M, Holländer J, Suominen J, Yliruusi J, Sandler N. 3D printed drug delivery devices: perspectives and technical challenges. Expert Rev Med Dev 2017;14:685–696. [CrossRef]
  • [14] Nikolova MP, Chavali MS. Recent advances in biomaterials for 3D scaffolds: A review. Bioact Mater 2019;4:271–292. [CrossRef]
  • [15] Wang Y, Wang X, Shi J, Zhu R, Zhang J, Zhang Z, et al. A biomimetic silk fibroin/sodium alginate composite scaffold for soft tissue engineering. Sci Rep 2016;6:1–13. [CrossRef]
  • [16] Shen W, Hsieh YL. Biocompatible sodium alginate fibers by aqueous processing and physical crosslinking. Carbohydr Polym 2014;102:893–900. [CrossRef]
  • [17] Wu J, Wei W, Wang LY, Su ZG, Ma GH. A thermosensitive hydrogel based on quaternized chitosan and poly (ethylene glycol) for nasal drug delivery system. Biomaterials 2007;28:2220–2232. [CrossRef]
  • [18] Chiu YC, Larson JC, Isom Jr A, Brey EM. Generation of porous poly (ethylene glycol) hydrogels by salt leaching. Tissue Eng Part C Methods 2010;16:905–912. [CrossRef]
  • [19] Chen BY, Jing X, Mi HY, Zhao H, Zhang WH, Peng XF, et al. Fabrication of polylactic acid/polyethylene glycol (PLA/PEG) porous scaffold by supercritical CO 2 foaming and particle leaching. Polym Eng Sci 2015;55:1339–1348. [CrossRef]
  • [20] You F, Wu X, Chen X. 3D printing of porous alginate/gelatin hydrogel scaffolds and their mechanical property characterization. Int J Polym Mater Polym Biomater 2017;66:299–306. [CrossRef]
  • [21] Cesur S, Cam ME, Sayin FS, Su S, Gunduz O. Controlled Release of Metformin Loaded Polyvinyl Alcohol (PVA) Microbubble/Nanoparticles Using Microfluidic Device for the Treatment of Type 2 Diabetes Mellitus. In IWBBIO 2020, May. pp. 185–193. [CrossRef]
  • [22] Pramono E, Utomo SB, Wulandari V, Clegg F. FTIR studies on the effect of concentration of polyethylene glycol on polimerization of Shellac. J Physics Conf Ser 2016;776: 012053. [CrossRef]
  • [23] Shameli K, Bin Ahmad M, Jazayeri SD, Sedaghat S, Shabanzadeh P, Jahangirian H, et al. Synthesis and characterization of polyethylene glycol mediated silver nanoparticles by the green method. Int J Mol Sci 2012;13:6639–6650. [CrossRef]
  • [24] Cesur S, Oktar FN, Ekren N, Kilic O, Alkaya DB, Seyhan SA et al. Preparation and characterization of electrospun polylactic acid/sodium alginate/orange oyster shell composite nanofiber for biomedical application. J Aust Ceram Soci 2020;56:533–543. [CrossRef]
  • [25] Murphy CM, O'Brien FJ. Understanding the effect of mean pore size on cell activity in collagen-glycosaminoglycan scaffolds. Cell Adh Migr 2010;4:377–381. [CrossRef]
  • [26] Li J, Shen S, Kong F, Jiang T, Tang C, Yin C. Effects of pore size on in vitro and in vivo anticancer efficacies of mesoporous silica nanoparticles. RSC Adv 2018;8:24633–24640. [CrossRef]
  • [27] Sultan S, Mathew AP. 3D printed scaffolds with gradient porosity based on a cellulose nanocrystal hydrogel. Nanoscale 2018;10:4421–4431. [CrossRef]
  • [28] Choi DJ, Park SJ, Gu BK, Kim YJ, Chung S, Kim CH. Effect of the pore size in a 3D bioprinted gelatin scaffold on fibroblast proliferation. J Ind Eng Chem 2018;67:388–395. [CrossRef]
  • [29] Egan PF. Integrated design approaches for 3D printed tissue scaffolds: Review and outlook. Materials 2019;12:2355. [CrossRef]
  • [30] Hutmacher DW, Schantz JT, Lam CXF, Tan KC, Lim TC. State of the art and future directions of scaffold‐based bone engineering from a biomaterials perspective. J Tissue Eng Regen Med 2007;1:245–260. [CrossRef]
  • [31] Samadzadeh S, Mousazadeh H, Ghareghomi S, Dadashpour M, Babazadeh M, Zarghami N. In vitro anticancer efficacy of Metformin-loaded PLGA nanofibers towards the post-surgical therapy of lung cancer. J Drug Deliv Sci Technol 2021;61:102318. [CrossRef]
  • [32] Swamy TM, Ramaraj B, Lee JH. Sodium alginate and its blends with starch: thermal and morphological properties. J Appl Polym Sci 2008;109:4075–4081. [CrossRef]
  • [33] AlKhatib HS, Taha MO, Aiedeh KM, Bustanji Y, Sweileh B. Synthesis and in vitro evaluation of iron-crosslinked N-methyl and N-benzyl hydroxamated derivatives of alginic acid as controlled release carriers. Eur Polym J 2006;42:2464–2474. [CrossRef]
  • [34] Barkat K, Ahmad M, Minhas MU, Khalid I, Mahmood A. Understanding mechanical characteristics of pH-responsive PEG 4000-based polymeric network for colorectal carcinoma: its acute oral toxicity study. Polym Bull 2020;127. [CrossRef]
  • [35] Bouriche S, Alonso-García A, Cárceles-Rodríguez CM, Rezgui F, Fernández-Varón E. An in vivo pharmacokinetic study of metformin microparticles as an oral sustained release formulation in rabbits. BMC Vet Res 2021;17:111. [CrossRef]
  • [36] Shelke NB, James R, Laurencin CT, Kumbar SG. Polysaccharide biomaterials for drug delivery and regenerative engineering. Polym Adv Technol 2014;25:448–460. [CrossRef]
  • [37] Giyatmi G, Eka Poetri TA, Irianto H, Fransiska D, Agusman A. Effect of alginate and polyethylene glycol addition on physical and mechanical characteristics of k-carrageenan-based edible film. Squalen Bullet Marine Fisheries Postharvest Biotechnol 2020;15:4151. [CrossRef]
  • [38] Zhu J, Ye H, Deng D, Li J, Wu Y. Electrospun metformin-loaded polycaprolactone/chitosan nanofibrous membranes as promoting guided bone regeneration membranes: Preparation and characterization of fibers, drug release, and osteogenic activity in vitro. J Biomater Appl 2020;34:1282–1293. [CrossRef]
  • [39] Ebrahimi L, Farzin A, Ghasemi Y, Alizadeh A, Goodarzi A, Basiri A, Ai J. Metformin-loaded PCL/PVA fibrous scaffold preseeded with human endometrial stem cells for effective guided bone regeneration membranes. ACS Biomater Sci Eng 2020;7:222231. [CrossRef]
  • [40] Das MK, Senapati PC. Furosemide-loaded alginate microspheres prepared by ionic cross-linking technique: Morphology and release characteristics. Indian J Pharm Sci 2008;70:77. [CrossRef]
  • [41] Ozoude CH, Azubuike CP, Ologunagba MO, Tonuewa SS, Igwilo CI. Formulation and development of metformin-loaded microspheres using Khaya senegalensis (Meliaceae) gum as co- polymer. Future J Pharm Sci 2020;6:111. [CrossRef]
  • [42] Sriamornsak P, Nunthanid J, Cheewatanakornkool K, Manchun S. Effect of drug loading method on drug content and drug release from calcium pectinate gel beads. AAPS Pharm Sci Tech 2010;11:1315–1319. [CrossRef]
There are 43 citations in total.

Details

Primary Language English
Subjects Biochemistry and Cell Biology (Other)
Journal Section Research Articles
Authors

Sena Harmancı This is me 0000-0001-9709-1735

Sümeyye Cesur 0000-0001-5050-1303

Oğuzhan Gündüz 0000-0002-9427-7574

Cem Bülent Üstündağ 0000-0002-4439-0878

Publication Date December 29, 2023
Submission Date November 3, 2021
Published in Issue Year 2023 Volume: 41 Issue: 6

Cite

Vancouver Harmancı S, Cesur S, Gündüz O, Üstündağ CB. Controlled release of metformin-loaded SA/PEG scaffolds produced by 3d-printing technology. SIGMA. 2023;41(6):1106-14.

IMPORTANT NOTE: JOURNAL SUBMISSION LINK https://eds.yildiz.edu.tr/sigma/