Fabrication and Characterization of Electrospun Nanofibers for the Modified Release of the Chronobiotic Hormone Melatonin

Author(s): Marilena Vlachou*, Stefanos Kikionis, Angeliki Siamidi, Konstantina Tragou, Stefania Kapoti, Efstathia Ioannou, Vassilios Roussis, Andrew Tsotinis.

Journal Name: Current Drug Delivery

Volume 16 , Issue 1 , 2019

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Graphical Abstract:


Abstract:

Objective: Aiming at the modified release of melatonin (MLT), electrospun-MLT loaded nanofibers, filled into hard gelatin and DRcapsTM capsules, were used as formulants.

Methods: Cellulose acetate, polyvinylpyrrolidinone and hydroxypropylmethylcellusose (HPMC 2910) were used for the preparation of the fiber matrices through electrospinning. The in vitro modified release profile of MLT from the fabricated matrices in gastrointestinal-like fluids was studied. At pH 1.2, the formulations CA1, CA2, PV1, HP1, HP2 and the composite formulations CAPV1-CAPV5 in hard gelatin capsules exhibited fast MLT release.

Results: In general, the same trend was observed at pH 6.8, with the exception of CAPV1 and CAPV2. These two composite formulations delivered 52.08% and 75.25% MLT, respectively at a slower pace (6 h) when encapsulated in DRcapsTM capsules. In all other cases, the release of MLT from DRcapsTM capsules filled with the MLT-loaded nanofibers reached 100% at 6h.

Conclusion: These findings suggest that the MLT-loaded nanofibrous mats developed in this study exhibit a promising profile for treating sleep dysfunctions.

Keywords: Electrospun nanofibers, polymers, scanning electron microscopic images, melatonin, capsules, modified release.

[1]
Korf, H.W.; von Gall, C. Mice, melatonin and the circadian system. Mol. Cell. Endocrinol., 2006, 252, 57-68.
[2]
Vlachou, M.; Eikosipentaki, A.; Xenogiorgis, V. Pineal hormone melatonin: Solubilization studies in model aqueous gastrointestinal environments. Cur. Drug Deliv., 2006, 3, 255-265.
[3]
Kalsbeek, A.; Buijs, R.M. Output pathways of the mammalian suprachiasmatic nucleus: Coding circadian time by transmitter selection and specific targeting. Cell Tissue Res., 2002, 309, 109-118.
[4]
Brzezinski, A. Melatonin in humans. N. Engl. J. Med., 1997, 336, 186-195.
[5]
Dubocovich, M.L.; Rivera-Bermudez, M.A.; Gerdin, M.J.; Masana, M.I. Molecular pharmacology, regulation and function of mammalian melatonin receptors. Front. Biosci., 2003, 8, 1093-1108.
[6]
Skene, D.J.; Arendt, J. Human circadian rhythms: Physiological and therapeutic relevance of light and melatonin. Ann. Clin. Biochem., 2006, 43, 344-353.
[7]
Wyatt, J.K.; Dijk, D.J.; Ritz De, C.A.; Ronda, J.M. Czeisler. C.A. Sleep-facilitating effect of exogenous melatonin in healthy young men and women is circadian-phase dependent. Sleep, 2006, 29, 609-618.
[8]
Vlachou, M.; Ioannidou, V.; Vertzoni, M.; Tsotinis, A.; Afroudakis, P.; Sugden, D. Controlled release from solid pharmaceutical formulations of two nalkanoyl-4-methoxybicyclo [4.2.0]octa-1,3,5-trien-7-ethanamines with melatoninergic activity. Lett. Drug Des. Discov., 2015, 12, 259-262.
[9]
Vlachou, M.; Siamidi, A.; Pareli, I.; Zampakola, A.; Konstantinidou, S. An account of modified release of melatonin from compression-coated, uncoated and bilayer tablets. J. Pharm. Pharm. Sci., 2016, 1, 10-14.
[10]
Vlachou, M.; Siamidi, A.; Konstantinidou, S.; Dotsikas, Y. Optimization of controlled release matrix formulation of melatonin via experimental design. J. Pharm. Drug Deliv. Res., 2016, 5, 1-5.
[11]
Vlachou, M.; Papamichael, M.; Siamidi, A.; Fragouli, I.; Afroudakis, P.A.; Kompogennitaki, R.; Dotsikas, Y. Comparative in vitro controlled release studies on the chronobiotic hormone melatonin from cyclodextrins-containing matrices and cyclodextrin: Melatonin complexes. Int. J. Mol. Sci., 2017, 18, 1641.
[12]
Vlachou, M.; Tragou, T.; Siamidi, A.; Kikionis, S.; Chatzianagnostou, A.L.; Mitsopoulos, A.; Ioannou, E.; Roussis, V.; Tsotinis, A. Modified in vitro release of the chronobiotic hormone melatonin from matrix tablets based on the marine sulfated polysaccharide ulvan. J. Drug Deliv. Sci. Technol., 2018, 44, 41-48.
[13]
Zampakola, A.; Siamidi, A.; Pippa, N.; Demetzos, C.; Vlachou, M. Chronobiotic hormone melatonin: Comparative in vitro release studies from matrix tablets and liposomal formulations. Lett. Drug Des. Discov., 2017, 14, 476-480.
[14]
Kumar, A.; Agarwal, S.P.; Khanna, R. Modified release bi-layered tablet of melatonin using β-cyclodextrin. Pharmazie, 2008, 58, 642-644.
[15]
Kikionis, S.; Ioannou, E.; Toskas, G.; Roussis, V. Electrospun biocomposite nanofibers of ulvan/PCL and ulvan/PEO. J. Appl. Polym. Sci., 2015, 132, 42153.
[16]
Al-Enizi, A.M.; Zagho, M.M.; Elzatahry, A.A. Polymer-based electrospun nanofibers for biomedical applications. Nanomaterials , 2018, 8, 259.
[17]
Cheng, H.; Yang, X.; Che, X.; Yang, M.; Zhai, G. Biomedical application and controlled drug release of electrospun fibrous materials. Mater. Sci. Eng. C, 2018, 90, 750-763.
[18]
Kenry; Lim, C.T. Nanofiber technology: Current status and emerging developments. Prog. Polym. Sci., 2017, 70, 1-17.
[19]
Chang, L.; Hu, J.; Chen, F.; Chen, Z.; Shi, J.; Yang, Z.; Li, Y.; Lee, L.J. Nanoscale bio-platforms for living cell interrogation: Current status and future perspectives. Nanoscale, 2016, 8, 3181-3206.
[20]
Gallego-Perez, D.; Chang, L.; Shi, J.; Ma, J.; Kim, S-H.; Zhao, X.; Malkoc, V.; Wang, X.; Minata, M.; Kwak, K.J.; Wu, Y.; Lafyatis, G.P.; Lu, W.; Hansford, D.J.; Nakano, I.; Lee, L.J. On-chip clonal analysis of glioma-stem-cell motility and therapy resistance. Nano Lett., 2016, 16, 5326-5332.
[21]
Bhardwaj, N.; Kundu, S. Electrospinning: A fascinating fiber fabrication technique. Biotech. Adv., 2010, 28, 325-347.
[22]
Greiner, A.; Wendorff, J.H. Electrospinning: A fascinating method for the preparation of ultrathin fibers. Angew. Chem. Int. Ed., 2007, 46, 5670-5703.
[23]
Teo, W.E.; Ramakrishna, S.A. Review on electrospinning design and nanofibre assemblies. Nanotechnology, 2006, 17, 89-106.
[24]
Agarwal, S.; Wendorff, J.H.; Greiner, A. Use of electrospinning technique for biomedical applications. Polymer , 2008, 49, 5603-5621.
[25]
Chakraborty, S.; Liao, I.C.; Adler, A.; Leong, K.W. A facile technique to fabricate drug delivery systems. Adv. Drug Deliv. Rev., 2009, 61, 1043-1054.
[26]
Ramakrishna, S.; Fujihara, K.; Teo, W.E.; Yong, T.; Ma, Z.; Ramaseshan, R. Electrospun nanofibers: solving global issues. Mater. Today, 2006, 9, 40-50.
[27]
Hu, X.; Liu, S.; Zhou, G.; Huang, Y.; Xie, Z.; Jing, X. Electrospinning of polymeric nanofibers for drug delivery applications. J. Control. Release, 2014, 185, 12-21.
[28]
Joshi, D.; Garg, T.; Goyal, A.K.; Rath, G. Development and characterization of novel medicated nanofibers against periodontitis. Curr. Drug Deliv., 2015, 5, 564-577.
[29]
Singh, A.; Rath, G.; Singh, R.; Goyal, A.K. Nanofibers: An effective tool for controlled and sustained drug delivery. Curr. Drug Deliv., 2018, 2, 155-166.
[30]
Akhgari, A.; Shakib, Z.; Sanati, S. Review on electrospun nanofibers for oral drug delivery. Nanomed. J., 2017, 4, 197-207.
[31]
Kikionis, S.; Ioannou, E.; Andrén, O.C.J.; Chronakis, I.; Fahmi, A.; Malkoch, M.; Toskas, G.; Roussis, V. Nanofibrous nonwovens based on dendritic-linear-dendritic poly (ethylene glycol) hybrids. J. Appl. Polym. Sci., 2017, 135, 45949.
[32]
Kikionis, S.; Ioannou, E.; Konstantopoulou, M.; Roussis, V. Electrospun micro/nanofibers as controlled release systems for pheromones of Bactrocera oleae and Prays oleae. J. Chem. Ecol., 2017, 43, 254-262.
[33]
Toskas, G.; Hund, R.D.; Laourine, E.; Cherif, C.; Smyrniotopoulos, V.; Roussis, V. Nanofibers based on polysaccharides from the green seaweed Ulva rigida. Carbohydr. Polym., 2011, 84, 1093-1102.
[34]
Toskas, G.; Heinemann, S.; Heinemann, C.; Cherif, C.; Hund, R.D.; Roussis, V.; Hanke, T. Ulvan and ulvan/chitosan polyelectrolyte nanofibrous membranes as a potential substrate material for the cultivation of osteoblasts. Carbohydr. Polym., 2012, 89, 997-1002.
[35]
Ignatious, F.; Sun, L.; Lee, C-P.; Baldoni, J. Electrospun nanofibers in oral drug delivery. Pharm. Res., 2010, 27, 576-588.
[36]
Thakkar, S.; Misra, M. Electrospun polymeric nanofibers: New horizons in drug delivery. Eur. J. Pharm. Sci., 2017, 107, 148-167.
[37]
Sinko, P.J.; Singh, Y. Martin’s Physical Pharmacy and Pharmaceutical Sciences, 6th ed; Lippincott Williams & Wilkins: Baltimore, 2011.
[38]
Balogh, A. Farkas, B.; Verreck, G.; Mensch, J.; Borbás, E.; Nagy, B.; Marosi, G.; Nagy, Z.K. AC and DC electrospinning of hydroxypropylmethylcellulose with polyethylene oxides as secondary polymer for improved drug dissolution. Int. J. Pharm., 2016, 30, 159-166.
[39]
Paaver, U.; Heinämäki, J.; Laidmäe, I.; Lust, A.; Kozlova, J.; Sillaste, E.; Kirsimäe, K.; Veski, P.; Kogermann, K. Electrospun nanofibers as a potential controlled-release solid dispersion system for poorly water-soluble drugs. Int. J. Pharm., 2015, 479, 252-260.
[40]
Verreck, G.; Chun, I.; Peeters, J.; Rosenblatt, J.; Brewster, M.E. Preparation and characterization of nanofibers containing amorphous drug dispersions generated by electrostatic spinning. Pharm. Res., 2003, 20, 810-817.
[41]
Skoug, J.W.; Borin, M.T.; Fleishaker, J.C.; Cooper, A.M. In vitro and in vivo evaluation of whole and half tablets of sustained-release adinazolam mesylate. Pharm. Res., 1991, 8, 1482-1488.
[42]
Cole, E.T.; Scott, R.A. Connor. A.L.; Wilding, B.R.; Petereit, H.U.; Schminke, C.; Beckert, T.; Cadé, D. Enteric coated HPMC capsules designed to achieve intestinal targeting. Int. J. Pharm., 2002, 231, 83-95.
[43]
Al-Tabakha, M.M.; Arida, A.I.; Fahelelbom, K.M.S.; Sadek, B.; Jarad, R.A.A. Performances of new generation of delayed release capsules. J. Young Pharm., 2015, 7, 36-44.


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Article Details

VOLUME: 16
ISSUE: 1
Year: 2019
Page: [79 - 85]
Pages: 7
DOI: 10.2174/1567201815666180914095701

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