Fabrication and characterization of carbamazepine-loaded nanofibers for controlled drug delivery
DOI:
https://doi.org/10.20450/mjcce.2025.2802Keywords:
Carbamazepine; electrospun nanofiber; epilepsy, drug deliveryAbstract
Carbamazepine (CBZ) is a widely prescribed antiepileptic and mood stabilizing drug. However, its limited water solubility and low bioavailability challenge its effective use. This study focused on the fab-rication and characterization of CBZ-loaded polylactic acid (PLA) / polyethylene glycol (PEG) fibers for controlled drug delivery. The morphology and diameter of the fibers were characterized using scanning electron microscopy (SEM) and Fourier transforms infrared spectroscopy (FTIR) confirmed the success-ful encapsulation of CBZ within the fibers. Differential scanning calorimetry (DSC) analysis revealed the physical state of the drug in the fiber matrix. As a result of CBZ loading on fibers, the average fiber di-ameters were measured as ϕ = 1.177 ± 0.238 μm for 10 mg CBZ and ϕ = 1.119 ± 0.248 μm for 50 mg CBZ. It was observed that the increase in electrical conductivity due to an increasing drug concentration, caused a decrease in fiber diameter. When drug release results were analyzed, the fibers showed a con-trolled release profile extending up to 10 h. These results suggest that the fabricated CBZ-loaded PLA/PEG fibers hold promise as a controlled drug delivery system for CBZ, offering the potential for en-hanced therapeutic efficacy, reduced side effects, and improved patient compliance.
References
(1) Pant, B.; Park, M.; Kim, A. A., Electrospun nanofibers for dura mater regeneration: A Mini Review on Current Progress. Pharmaceutics 2023, 15(5), 1347.
https://doi.org/10.3390/pharmaceutics15051347.
(2) Ramos, R. C., Investigating electrospinning to prepare nanofibers suitable for neurological disorders, Univer-sidade de Lisboa Faculdade de Farmácia, Tese de Mes-trado Integrado em Ciências Farmacêuticas 2020, pp.9–32.
(3) Halliday, A. J.; Moulton, S. E.; Wallace, G. G.; Cook, M. J., Novel methods of antiepileptic drug delivery-polymer-based implants. Adv. Drug Deliv. Rev. 2012, 64 (10), 953–964.
https://doi.org/10.1016/j.addr.2012.04.004
(4) Sun, J. J.; Xie, L.; Liu, X. D., Transport of carbamaze-pine and drug interactions at blood‐brain barrier. Acta Pharmacol. Sin. 2006, 27 (2), 249–253.
https://doi.org/10.1111/j.1745-7254.2006.00246.x
(5) Liu, S.; Yang, S.; Ho, P. C., Intranasal administration of carbamazepine-loaded carboxymethyl chitosan nanopar-ticles for drug delivery to the brain. Asian J. Pharm. Sci. 2018, 13 (1), 72–81.
https://doi.org/10.1016/j.ajps.2017.09.001
(6) Abedinoghli, D.; Charkhpour, M.; Osouli-Bostanabad, K.; Selselehjonban, S.; Emami, S.; Barzegar-Jalali, M.; Adibkia, K., Electrosprayed nanosystems of carbamaze-pine–PVP K30 for enhancing its pharmacologic effects. Iran J. Pharm. Res. 2018, 17 (4), 1431.
(7) Milović, M.; Djuriš, J.; Djekić, L.; Vasiljević, D.; Ibrić, S., Characterization and evaluation of solid self-microemulsifying drug delivery systems with porous carriers as systems for improved carbamazepine release. Int. J. Pharm. 2012, 436 (1–2), 58–65.
https://doi.org/10.1016/j.ijpharm.2012.06.032
(8) Hu, J.; Johnston, K. P.; Williams III, R. O. Spray freez-ing into liquid (SFL) particle engineering technology to enhance dissolution of poorly water soluble drugs: or-ganic solvent versus organic/aqueous co-solvent sys-tems. Eur. J. Pharm. Sci. 2003, 20 (3), 295–303.
https://doi.org/10.1016/S0928-0987(03)00203-3
(9) Friedrich, H.; Fussnegger, B.; Kolter, K.; Bodmeier, R., Dissolution rate improvement of poorly water-soluble drugs obtained by adsorbing solutions of drugs in hy-drophilic solvents onto high surface area carriers. Eur. J. Pharm. Biopharm. 2006, 62 (2), 171–177.
https://doi.org/10.1016/j.ejpb.2005.08.013
(10) Jahangiri, A.; Barzegar-Jalali, M.; Javadzadeh, Y.; Ham-ishehkar, H.; Adibkia, K., Physicochemical characteriza-tion of atorvastatin calcium/ezetimibe amorphous nano-solid dispersions prepared by electrospraying method. Artif. Cells Nanomed. Biotechnol. 2017, 45, 1138–45. https://doi.org/10.1080/21691401.2016.1202262
(11) Rana, H.; Jesadiya, B.; Mandal, S., Development of microemulsion for solubility enhancement of atorvas-tatin calcium. Int. J. Pharm. Sci. Res. 2013, 4 (8), 3103.
(12) Teixeira, M. C.; Carbone, C.; Souto, E. B., Beyond lipo-somes: Recent advances on lipid based nanostructures for poorly soluble/poorly permeable drug delivery. Prog. Lipid Res. 2017, 68, 1–11.
https://doi.org/10.1016/j.plipres.2017.07.001
(13) Kudo, S.; Takiyama, H., Solubility determination for carbamazepine and saccharin in methanol/water mixed solvent: basic data for design of cocrystal production by antisolvent crystallization. Journal of Chemical & Engi-neering Data 2018, 63 (2), 451–458.
https://doi.org/10.1021/acs.jced.7b00920.
(14) El-Zein, H.; Riad, L.; Abd El-Bary, A. Enhancement of carbamazepine dissolution: in vitro and in vivo evalua-tion. Int. J. Pharm. 1998, 168(2), 209–220.
https://doi.org/10.1016/S0378-5173(98)00093-3
(15) Nan, Z.; Lijun, G.; Tao, W.; Dongqin, Q., Evaluation of carbamazepine (CBZ) supersaturatable self-microemulsifying (S-SMEDDS) formulation in-vitro and in-vivo. Iran J. Pharm. Res. 2012, 11(1), 257.
(16) Gandhi, A. V.; Thipsay, P.; Kirthivasan, B.; Squillante, E., Adsorption onto mesoporous silica using supercriti-cal fluid technology improves dissolution rate of car-bamazepine — a poorly soluble compound. Aaps Pharmscitech. 2017, 18, 3140–3150.
https://doi.org 10.1208/s12249-017-0784-3
(17) Halliwell, R. A.; Bhardwaj, R. M.; Brown, C. J.; Briggs, N. E.; Dunn, J.; Robertson, J.; Nordon, A.; Florence, A. J., Spray drying as a reliable route to produce metastable carbamazepine form IV. J. Pharm. Sci. 2017, 106 (7), 1874–1880. https://doi.org/10.1016/j.xphs.2017.03.045
(18) Barakat, N. S.; Radwan, M. A., In vitro performance of carbamazepine loaded to various molecular weights of poly(D,L-lactide-co-glycolide). Drug deliv. 2006, 13 (1), 9–18. https://doi.org/10.1080/10717540500308992
(19) Meer, T. A.; Baig, M. S.; Amin, P. D., Preparation and evaluation of carbamazepine loaded fibrous electrospun mats of starch. J. Pharm. Investig. 2015, 45, 301–309. https://doi.org:10.1007/s40005-015-0176-1
(20) Ana, R.; Mendes, M.; Sousa, J.; Pais, A.; Falcão, A.; Fortuna, A.; Vitorino, C., Rethinking carbamazepine oral delivery using polymer-lipid hybrid nanoparticles. Int. J. Pharm. 2019, 554, 352–365.
https://doi.org/10.1016/j.ijpharm.2018.11.028
(21) Sepasi, T.; Ghadiri, T.; Bani, F.; Ebrahimi-Kalan, A.; Khodakarimi, S.; Zarebkohan, A.; Gorji, A., Nanotech-nology-based approaches in diagnosis and treatment of epilepsy. J. Nanopart Res. 2022, 24 (10), 199.
https://doi.org/10.1007/s11051-022-05557-6
(22) Wei, L.; Guo, X. Y.; Yang, T.; Yu, M. Z.; Chen, D. W.; Wang, J. C., Brain tumor-targeted therapy by systemic delivery of siRNA with Transferrin receptor-mediated core-shell nanoparticles. Int. J. Pharm. 2016, 510 (1), 394–405. https://doi.org/10.1016/j.ijpharm.2016.06.127
(23) Meng, F.; Asghar, S.; Xu, Y.; Wang, J.; Jin, X.; Wang, Z.; Wang, J.; Ping, Q.; Zhou, Y.; Xiao, Y., Design and evaluation of lipoprotein resembling curcumin-encapsulated protein-free nanostructured lipid carrier for brain targeting. Int. J. Pharm. 2016, 506 (1–2), 46–56. https://doi.org/10.1016/j.ijpharm.2016.04.033
(24) Bauquier, S. H.; Jiang, J. L.; Yue, Z.; Lai, A.; Chen, Y.; Moulton, S. E.; McLean, K. J.; Vogrin, S.; Halliday, A. J.; Wallace, G.; Cook, M. J., Antiepileptic effects of la-cosamide loaded polymers implanted subdurally in GAERS. Int. J. Polymer Sci. 2016, Article ID 6594960. https://doi.org/10.1155/2016/6594960
(25) Chen, Y.; Gu, Q.; Yue, Z.; Crook, J. M.; Moulton, S. E.; Cook, M. J.; Wallace, G. G., Development of drug-loaded polymer microcapsules for treatment of epilepsy. Biomater Sci. 2017, 5(10), 2159–2168.
https://doi.org/10.1039/C7BM00623C
(26) Williamson, A.; Rivnay, J.; Kergoat, L.; Jonsson, A.; Inal, S.; Uguz, I.; Ferro, M.; Ivanov, A.; Sjöström, T. A.; Simon, D. T.; Berggren, M.; Malliaras, G. G.; Bernard, C., Controlling epileptiform activity with organic elec-tronic ion pumps. Adv. Mater. 2015, 27 (20), 3138–3144. https://doi.org/10.1002/adma.201500482
(27) Halliday, A. J.; Campbell, T. E.; Nelson, T. S.; McLean, K. J.; Wallace, G. G.; Cook, M. J., Levetiracetam-loaded biodegradable polymer implants in the tetanus toxin model of temporal lobe epilepsy in rats. J. Clin. Neurosci. 2013, 20 (1), 148–152.
https://doi.org/10.1016/j.jocn.2012.05.017
(28) Pritchard, E. M.; Szybala, C.; Boison, D.; Kaplan, D. L., Silk fibroin encapsulated powder reservoirs for sustained release of adenosine. J. Contr. Release. 2010, 144 (2), 159–167. https://doi.org/10.1016/j.jconrel.2010.01.035
(29) Monfared, M.; Taghizadeh, S.; Zare-Hoseinabadi, A.; Mousavi, S. M.; Hashemi, S. A.; Ranjbar, S.; Amani, A. M., Emerging frontiers in drug release control by core–shell nanofibers: review. Drug. Metab. Rev. 2019, 51 (4), 589–611.
https://doi.org/10.1080/03602532.2019.1642912
(30) Contreras-Cáceres, R.; Cabeza, L.; Perazzoli, G.; Díaz, A.; López-Romero, J. M.; Melguizo, C.; Prados, J., Electrospun nanofibers: Recent applications in drug de-livery and cancer therapy. Nanomaterials. 2019, 9 (4), 656. https://doi.org/10.3390/nano9040656
(31) Esentürk, İ.; Erdal, M. S.; Güngör, S. Electrospinning method to produce drug-loaded nanofibers for topi-cal/transdermal drug delivery applications. Istanbul J Pharm. 2016, 46 (1), 49-69.
(32) Sahu, D. K.; Ghosh, G.; Rath, G., Nanofibers in drug delivery. Nanopharmaceutical Advanced Delivery Sys-tems. 2021, 99–123.
https://doi.org/10.1002/9781119711698.ch5
(33) Cesur, S.; Oktar, F. N.; Ekren, N.; Kilic, O.; Alkaya, D. B.; Seyhan, S. A.; Ege, Z. R.; Lin, C.; Kuruca, S. E.; Er-demir, G.; Gunduz, O., Preparation and characterization of electrospun polylactic acid/sodium alginate/orange oyster shell composite nanofiber for biomedical applica-tion. J Aust Ceram Soc. 2020, 56, 533–543.
https://doi.org/10.1007/s41779-019-00363-1
(34) Mundel, R.; Thakur, T.; Chatterjee, M., Emerging uses of PLA–PEG copolymer in cancer drug delivery. 3 Bio-tech. 2022, 12 (2), 41.
https://doi.org/10.1007/s13205-021-03105-y
(35) Seyhan, S. A.; Alkaya, D. B.; Cesur, S.; Sahin, A., In-vestigation of the antitumor effect on breast cancer cells of the electrospun amygdalin-loaded poly(l-lactic ac-id)/poly(ethylene glycol) nanofibers. Int. J. Biol. Mac-romol. 2023, 239, 124201.
https://doi.org/10.1016/j.ijbiomac.2023.124201
(36) Nepomuceno, N. C.; Barbosa, M. A.; Bonan, R. F.; Oliveira, J. E.; Sampaio, F. C.; Medeiros, E. S., Antimi-crobial activity of PLA/PEG nanofibers containing ter-pinen‐4‐ol against Aggregatibacter actinomycetemcomi-tans. J. Appl. Polym. Sci. 2018, 135 (6), 45782. https://doi.org/10.1002/app.45782.
(37) Aboutalebi Anaraki, N.; Roshanfekr Rad, L.; Irani, M.; Haririan, I., Fabrication of PLA/PEG/MWCNT electro-spun nanofibrous scaffolds for anticancer drug delivery. J. Appl. Polym. Sci. 2015, 132 (3).
https://doi.org/10.1002/app.41286
(38) Ayaz Seyhan, S.; Demirel, A. B.; Cesur, S.; Bilgic Al-kaya, D., Production, characterization, and antioxidant activity evaluation of Rheum ribes L. Extract-Loaded PLA/PEG Nanofibers. J. Res. Pharm. 2023, 27, 146–156. https:10.29228/jrp.299
(39) Cesur, S.; Ulag, S.; Ozak, L.; Gumussoy, A.; Arslan, S.; Yilmaz, B. K.; Ekren, N.; Agirbasli, M.; Kalaskar, D. M.; Gunduz, O., Production and characterization of elas-tomeric cardiac tissue-like patches for Myocardial Tissue Engineering. Polymer Testing. 2020, 90, 106613. https://doi.org/10.1016/j.polymertesting.2020.106613
(40) Barakat, N. S.; Elbagory, I. M.; Almurshedi, A. S., Con-trolled-release carbamazepine matrix granules and tab-lets comprising lipophilic and hydrophilic components. Drug deliv. 2009, 16 (1), 57–65.
https://doi.org/10.1080/10717540802518157
(41) Wang, F.; Sun, Z.; Yin, J.; Xu, L. Preparation, character-ization and properties of porous PLA/PEG/Curcumin composite nanofibers for antibacterial application. Na-nomaterials 2019, 9 (4), 508.
https://doi.org/10.3390/nano9040508
(42) Musuc, A. M.; Anuta, V.; Atkinson, I.; Sarbu, I.; Popa, V. T.; Munteanu, C.; Mircioiu, C.; Ozon, E. A.; Ni-tulescu, G. M.; Mitu, M. A., Formulation of chewable tablets containing carbamazepine-β-cyclodextrin inclu-sion complex and f-melt disintegration excipient. The mathematical modeling of the release kinetics of car-bamazepine. Pharmaceutics. 2021, 13 (6), 915.
https://doi.org/10.3390/pharmaceutics13060915
(43) Feng, Z.; Li, M.; Wang, W., Improvement of dissolu-tion and tablet ability of carbamazepine solid dispersions with high drug loading prepared by hot-melt extrusion. Pharm.- Int. J. Pharm. Sci. 2019, 74 (9), 523–528. https://doi.org/10.1691/ph.2019.9008
(44) Smith, J. S.; MacRae, R. J.; Snowden, M. J., Effect of SBE7-β-cyclodextrin complexation on carbamazepine release from sustained release beads. Eur. J. Pharm. Bi-opharm. 2005, 60 (1), 73–80.
https://doi.org/10.1016/j.ejpb.2004.12.001
(45) Chou, S. F.; Carson, D.; Woodrow, K. A., Current strat-egies for sustaining drug release from electrospun nano-fibers. J. Control. Release. 2015, 220, 584–591.
https://doi.org/10.1016/j.jconrel.2015.09.008
(46) Xie, Z.; Buschle‐Diller, G. Electrospun poly (D, L‐lactide) fibers for drug delivery: The influence of cosol-vent and the mechanism of drug release. J. Appl. Polym. Sci. 2010, 115 (1), 1–8.
https://doi.org/10.1002/app.31026
(47) Chen, S. C.; Huang, X. B.; Cai, X. M.; Lu, J.; Yuan, J.; Shen, J., The influence of fiber diameter of electrospun poly(lactic acid) on drug delivery. Fibers Polym. 2012, 13, 1120–1125.
Downloads
Published
Versions
- 2025-06-29 (2)
- 2025-06-23 (1)
How to Cite
Issue
Section
License
Copyright (c) 2025 Dilek Bilgic Alkaya, Serap Ayaz Seyhan
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
