Abstract
Metronidazole (MTZ) loaded Eudragit S-100 (ES-100) nonwoven nanofibrous mats were successfully electrospun and evaluated for intestinal drug delivery. MTZ was varied in the range of 1–15% (w/w) in ES-100 nanofibrous mats, the morphological characterization of nanofibrous mats was carried out using FE-SEM and the average diameter of nanofiber was found in the range 150–600 nm. WAXD and DSC demonstrated the amorphous nature of MTZ in ES-100 nanofibrous mats. Their contact angle analysis confirmed the hydrophobic nature. The mechanical strength of ES-100 nanofibrous mats decreased with increasing MTZ concentration. The drug release profiles showed 74% MTZ release from ES-100d within 2 h at pH 6.8 which is the colonic environment. Antibacterial activities against gram-positive bacteria (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli) showed that the ES-100 nanofibrous mats loaded with MTZ exhibited good activity.
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Patel M, Shah T, Amin A. Therapeutic opportunities in colon-specific drug-delivery systems. Crit Rev Ther Drug Carr Syst. 2007;24:147.
Asghar LF, Chandran S. Design and evaluation of pH modulated controlled release matrix systems for colon specific delivery of indomethacin. Pharmazie. 2008;63:736.
Beloqui A, Coco R, Memvanga PB, Ucakar B, des Rieux A, Préat V. pH-sensitive nanoparticles for colonic delivery of curcumin in inflammatory bowel disease. Int J Pharm. 2014;473:203.
Canavan C, Abrams KR, Mayberry JF. Meta-analysis: mortality in Crohn’s disease. Aliment Pharmacol Ther. 2007;25:861.
Bonadiesa I, Maglione L, Ambrogi V, Paccez JD, Zerbini LF, Luiz F, Rocha e silva LF, Picanço NS, Wanderli PT, Grafova I, Grafov A, Carfagna C. Electrospun core/shell nanofibers as designed devices for efficient Artemisinin delivery. Eur Poly J. 2017;89:211.
Moreno I, González-González V, Romero-García J. Control release of lactate dehydrogenase encapsulated in poly (vinyl alcohol) nanofibers via electrospinning. Eur Polym J. 2011;47:1264.
Zamani M, Morshed M, Varshosaz J, Jannesari M. Controlled release of metronidazole benzoate from poly e-caprolactone electrospun nanofibers for periodontal diseases. Eur J Pharm Biopharm. 2010;75:179.
Kim K, Luu YK, Chang C, Fang D, Hsiao BS, Chu B, Hadjiargyrou M. Incorporation and controlled release of a hydrophilic antibiotic using poly(lactide-co-glycolide)-based electrospun nanofibrous scaffolds. J Control Release. 2004;98:47.
Huang ZM, He CL, Yang A, Zhang Y, Han XJ, Yin J, Wu Q. Encapsulating drugs in biodegradable ultrafine fibers through co-axial electrospinning. J Biomed Mater Res A. 2006;77:169.
Verreck G, Chun I, Rosenblatt J, Peeters J, Dijck AV, Mensch J, Noppe M, Brewster ME. Incorporation of drugs in an amorphous state into electrospun nanofibers composed of a water-insoluble, nonbiodegradable polymer. J Control Release. 2003;92:349.
Reda RI, Wen MM, El-Kamel AH. Ketoprofen-loaded Eudragit electrospun nanofibers for the treatment of oral mucositis. Int J Nanomed. 2017;12:2335.
Laha A, Sharma CS, Majumdar S. Sustained drug release from multi-layered sequentially crosslinked electrospun gelatin nanofiber mesh. Mater Sci Eng C. 2017;76:782.
Lee H, Xu G, Kharaghani D, Nishino M, Song KH, Lee JS, Kim IS. Electrospun tri-layered zein/PVP-GO/zein nanofiber mats for providing biphasic drug release profiles. Int J Pharm. 2017;531:101.
Hamori M, Nagano K, Kakimoto S, Naruhashi K, Kiriyama A, Nishimura A, Shibata N. Preparation and pharmaceutical evaluation of acetaminophen nano-fiber tablets: application of a solvent-based electrospinning method for tableting. Biomed Pharmacother. 2016;78:14.
https://healthcare.evonik.com/en/products/pharmaceutical-excipients/solubility-enhancement
Hita V, Singh R, Jain SK. Colonic targeting of metronidazole using azo aromatic polymers: development and characterization. Drug Del. 1997;4:19.
Chacko M, Bhide SV. Carcinogenicity, perinatal carcinogenicity and teratogenicity of low dose metronidazole (MTZ) in Swiss mice. J Cancer Res Clin Oncol. 1986;112:135.
Chaber A. Okołooperacyjna profilaktyka antybiotykowa w chirurgii przewodu pokarmowego Antibiotic prophylaxis in alimentary tract surgery, w chirurgii przewodu pokarmowego. Wspó³czesna Onkologia. 1999;2:86.
Sadowska A, Krętowski R, Szynaka B, Cechowska-Pasko M, Car H. Metronidazole decreases viability of DLD-1 colorectal cancer cell line. Cancer Biother Radiopharm. 2013;28:615.
Turanli Y, Tort S, Acartürk F. Development and characterization of methylprednisolone loaded delayed release nanofibers. J Drug Del Sci Tech. 2019;49:58.
Ho MH, Chang HC, Chang YC, Claudia J, Lin TC, Chang PC. PDGF-metronidazole-encapsulated nanofibrous functional layers on collagen membrane promote alveolar ridge regeneration. Int J Nanomedicine. 2017;12:5525.
Schkarpetkin D, Reise M, Wyrwa R, Völpel A, Berg A, Schweder M, Schnabelrauch M, Watts DC, Sigusch BW. Development of novel electrospun dual-drug fiber mats loaded with a combination of ampicillin and metronidazole. Dent Mater. 2016;32:951.
Giram PS, Shitole A, Nande SS, Sharma N, Garnaik B. Fast dissolving moxifloxacin hydrochloride antibiotic drug from electrospun Eudragit L-100 nonwoven nanofibrous Mats. Mat Sci Eng C. 2018;92:526.
Shitole AA, Giram PS, Raut PW, Rade PP, Khandwekar AP, Sharma N, Garnaik B. Clopidrogel eluting electrospun Polyurethane/Polyethylene glycol thromboresistant, hemocompatible nanofibrous scaffolds. J Bio Appl. 2019;33:1327.
Zhang L, Yan J, Yin Z, Tang C, Guo Y, Li D, Wei B, Xu Y, GU Q, Wang L. Electrospun vancomycin-loaded coating on titanium implants for the prevention of implant associated infections. Int J Nanomedicine. 2014;9:3027.
Shen X, Yu D, Zhu L, Branford-White C, White K, Chatterton NP. Electrospun diclofenac sodium loaded Eudragit® L 100–55 nanofibers for colon-targeted drug delivery. Int J Pharm. 2011;408:200.
Yang DJ, **ong CD, Govender T, Wang YZ. Preparation and drug-delivery potential of metronidazole-loaded PELA triblock co-polymeric electrospun membranes. J Biomater Sci Polym Ed. 2009;20:1321.
Dewan I, Islam MM, Al-Hasan M, Nath J, Sultana S, Rana MS. Surface deposition and coalescence and coacervation phase separation methods: In Vitro Study and Compatibility Analysis of Eudragit RS30D, Eudragit RL30D, and Carbopol-PLA Loaded Metronidazole Microspheres. J Pharm (Cairo). 2015;2015:254930.
Mehta R, Chawla A, Sharma P, Pawar P. Formulation and in vitro evaluation of Eudragit S-100 coated naproxen matrix tablets for colon-targeted drug delivery system. J Adv Pharm Technol Res. 2013;4:31.
Payab S, Davaran S, Tanhaei A, Fayyazi B, Jahangiri A, Farzaneh A, Adibkia K. Triamcinolone acetonide–Eudragit® RS100 nanofibers and nanobeads: morphological and physicochemical characterization. Artif Cells Nanomed Biotechnol. 2016;44:362.
Chou SF, Woodrow KA. Relationships between mechanical properties and drug release from electrospun fibers of PCL and PLGA blends. J Mech Behav Biomed Mater. 2017;65:724.
Tort S, Acartürk F, Beşikci A. Evaluation of three-layered doxycycline-collagen loaded nanofiber wound dressing. Int J Pharm. 2017;529:642.
Tan EP, Ng SY, Lim CT. Tensile testing of a single ultrafine polymeric fiber. Biomaterials. 2005;13:1453.
Lim CT, Tan EPS, Ng SY. Effects of crystalline morphology on the tensile properties of electrospun polymer nanofibers. Appl Phys Lett. 2008;92:141908. https://doi.org/10.1063/1.2857478.
Han D, Steckl AJ. Selective pH-responsive core−sheath nanofiber membranes for chem/bio/med applications: targeted delivery of functional molecules. ACS Appl Mater Interfaces. 2017;9:42653.
Cesare FD, Mattia ED, Zussman E, Macagnano A. A study on the dependence of bacteria adhesion on the polymer nanofiber diameter. Environ Sci Nano. 2019;6:778.
Xue J, He M, Niu Y, Liu H, Crawford A, Coates P, Chen D, Shi R, Zhang L. Preparation and in vivo efficient anti-infection property of GTR/GBR implant made by metronidazole loaded electrospun polycaprolactone nanofiber membrane. Int J Pharm. 2014;475:566.
Acknowledgements
Ms. Priyanka P. Rade gratefully acknowledges the Department of Science and Technology, New Delhi, India for the award of DST-INSPIRE fellowship (IF160594) for her doctoral research. The authors also gratefully acknowledge LIA MATSUCAT, France for the collaboration. The authors express their heartfelt gratitude to Evonik Industries, Mumbai, India, for providing Eudragit S 100 as a gift sample.
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Rade, P.P., Giram, P.S., Shitole, A.A. et al. Physicochemical and in Vitro Antibacterial Evaluation of Metronidazole Loaded Eudragit S-100 Nanofibrous Mats for the Intestinal Drug Delivery. Adv. Fiber Mater. 4, 76–88 (2022). https://doi.org/10.1007/s42765-021-00090-y
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DOI: https://doi.org/10.1007/s42765-021-00090-y