Abstract
Several clinical studies have reported the analgesic effect of curcumin (Curc) in various situations such as rheumatoid arthritis, osteoarthritis, and postsurgical pain. Therefore, in this work, Curc-loaded electrospun nanofibers (NFs) are designed to evaluate their sustained release on analgesic effect duration in rats after epidural placement via repeated formalin and tail-flick tests. The Curc-loaded polycaprolactone/gelatin NFs (Curc-PCL/GEL NFs) are prepared through an electrospinning technique and introduced to the rat’s epidural space after laminectomy. The physicochemical and morphology features of the prepared Curc-PCL/GEL NFs were characterized via FE-SEM, FTIR, and degradation assay. The in vitro and in vivo concentrations of Curc were measured to evaluate the analgesic efficacy of the drug-loaded NFs. Rat nociceptive responses are investigated through repeated formalin and tail-flick tests for 5 weeks after the placement of NFs. Curc had a sustained release from the NFs for 5 weeks, and its local pharmaceutical concentrations were much greater than plasma concentrations. Rat’s pain scores in both early and late phases of the formalin test were remarkably decreased in the experimental period. Rat’s tail-flick latency was remarkably enhanced and remained constant for up to 4 weeks. Our findings show that the Curc-PCL/GEL NFs can supply controlled release of Curc to induce extended analgesia after laminectomy.
Similar content being viewed by others
Data Availability
The data that support the findings of this study are available from the corresponding author, upon reasonable request.
References
Wang, Y., Li, L., Ma, Y., Tang, Y., Zhao, Y., Li, Z., et al. (2020). Multifunctional supramolecular hydrogel for prevention of epidural adhesion after laminectomy. ACS Nano, 14(7), 8202–8219.
Peene, L., Le Cacheux, P., Sauter, A. R., Joshi, G. P., & Beloeil, H. (2021). Pain management after laminectomy: A systematic review and procedure-specific post-operative pain management (prospect) recommendations. European Spine Journal., 30(10), 2925–2935.
Foley, P. L., Liang, H., & Crichlow, A. R. (2011). Evaluation of a sustained-release formulation of buprenorphine for analgesia in rats. Journal of the American Association for Laboratory Animal Science., 50(2), 198–204.
Mishra, L., Nath, S., Gairola, R., Verma, R., & Mohanty, S. (2004). Buprenorphine-soaked absorbable gelatin sponge: An alternative method for postlaminectomy pain relief. Journal of Neurosurgical Anesthesiology., 16(2), 115–121.
Tseng, Y.-Y., Liao, J.-Y., Chen, W.-A., Kao, Y.-C., & Liu, S.-J. (2014). Biodegradable poly ([D, L]-lactide-co-glycolide) nanofibers for the sustainable delivery of lidocaine into the epidural space after laminectomy. Nanomedicine, 9(1), 77–87.
Eke-Okoro, U., Raffa, R., Pergolizzi Jr, J., Breve, F., Taylor Jr, R., Group NR. (2018). Curcumin in turmeric: basic and clinical evidence for a potential role in analgesia. Journal of Clinical Pharmacy and Therapeutics, 43(4), 460–466.
Gulsun, T., Inal, M., Akdag, Y., Izat, N., Oner, L., & Sahin, S. (2022). The development and characterization of electrospun gelatin nanofibers containing indomethacin and curcumin for accelerated wound healing. Journal of Drug Delivery Science and Technology., 67, 103000.
Pirmoradi, S., Fathi, E., Farahzadi, R., Pilehvar-Soltanahmadi, Y., & Zarghami, N. (2018). Curcumin affects adipose tissue-derived mesenchymal stem cell aging through TERT gene expression. Drug Research., 68(04), 213–221.
Rasouli, S., Montazeri, M., Mashayekhi, S., Sadeghi-Soureh, S., Dadashpour, M., Mousazadeh, H., et al. (2020). Synergistic anticancer effects of electrospun nanofiber-mediated codelivery of curcumin and chrysin: Possible application in prevention of breast cancer local recurrence. Journal of Drug Delivery Science and Technology., 55, 101402.
Wei, W., Zarghami, N., Abasi, M., Ertas, Y. N., & Pilehvar, Y. (2022). Implantable magnetic nanofibers with ON–OFF switchable release of curcumin for possible local hyperthermic chemotherapy of melanoma. Journal of Biomedical Materials Research Part A., 110(4), 851–860.
Mohebian, Z., Babazadeh, M., Zarghami, N., & Mousazadeh, H. (2021). Anticancer efficiency of curcumin-loaded mesoporous silica nanoparticles/nanofiber composites for potential postsurgical breast cancer treatment. Journal of Drug Delivery Science and Technology., 61, 102170.
Samadzadeh, S., Babazadeh, M., Zarghami, N., Pilehvar-Soltanahmadi, Y., & Mousazadeh, H. (2021). An implantable smart hyperthermia nanofiber with switchable, controlled and sustained drug release: Possible application in prevention of cancer local recurrence. Materials Science and Engineering: C., 118, 111384.
Tseng, Y.-Y., & Liu, S.-J. (2015). Nanofibers used for the delivery of analgesics. Nanomedicine, 10(11), 1785–1800.
Yosefifard, M., & Hassanpour-Ezatti, M. (2014). Epidural administration of neostigmine-loaded nanofibers provides extended analgesia in rats. DARU Journal of Pharmaceutical Sciences., 22(1), 1–10.
Pourpirali, R., Mahmoudnezhad, A., Oroojalian, F., Zarghami, N., & Pilehvar, Y. (2021). Prolonged proliferation and delayed senescence of the adipose-derived stem cells grown on the electrospun composite nanofiber co-encapsulated with TiO2 nanoparticles and metformin-loaded mesoporous silica nanoparticles. International Journal of Pharmaceutics., 604, 120733.
Kříž, N., Yamamotova, A., Tobiáš, J., & Rokyta, R. (2006). Tail-flick latency and self-mutilation following unilateral deafferentation in rats. Physiological Research, 55, 213–220.
Afolabi, A. O., Mudashiru, S. K., & Alagbonsi, I. A. (2013). Effects of salt-loading hypertension on nociception in rats. Journal of Pain Research., 6, 387.
Sun, J., Chen, F., Braun, C., Zhou, Y.-Q., Rittner, H., Tian, Y.-K., et al. (2018). Role of curcumin in the management of pathological pain. Phytomedicine, 48, 129–140.
Mashayekhi, S., Rasoulpoor, S., Shabani, S., Esmaeilizadeh, N., Serati-Nouri, H., Sheervalilou, R., et al. (2020). Curcumin-loaded mesoporous silica nanoparticles/nanofiber composites for supporting long-term proliferation and stemness preservation of adipose-derived stem cells. International journal of pharmaceutics., 587, 119656.
Serati-Nouri, H., Mahmoudnezhad, A., Bayrami, M., Sanajou, D., Tozihi, M., Roshangar, L., et al. (2021). Sustained delivery efficiency of curcumin through ZSM-5 nanozeolites/electrospun nanofibers for counteracting senescence of human adipose-derived stem cells. Journal of Drug Delivery Science and Technology., 66, 102902.
Tavakoli, F., Jahanban-Esfahlan, R., Seidi, K., Jabbari, M., Behzadi, R., Pilehvar-Soltanahmadi, Y., et al. (2018). Effects of nano-encapsulated curcumin-chrysin on telomerase, MMPs and TIMPs gene expression in mouse B16F10 melanoma tumour model. Artificial Cells, Nanomedicine, and Biotechnology., 46(sup2), 75–86.
Montazeri, M., Pilehvar-Soltanahmadi, Y., Mohaghegh, M., Panahi, A., Khodi, S., Zarghami, N., et al. (2017). Antiproliferative and apoptotic effect of dendrosomal curcumin nanoformulation in P53 mutant and wide-type cancer cell lines. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 17(5), 662–73.
Khodadadi, M., Alijani, S., Montazeri, M., Esmaeilizadeh, N., Sadeghi-Soureh, S., & Pilehvar-Soltanahmadi, Y. (2020). Recent advances in electrospun nanofiber-mediated drug delivery strategies for localized cancer chemotherapy. Journal of Biomedical Materials Research Part A., 108(7), 1444–1458.
Talaei, S., Mellatyar, H., Pilehvar-Soltanahmadi, Y., Asadi, A., Akbarzadeh, A., & Zarghami, N. (2019). 17-Allylamino-17-demethoxygeldanamycin loaded PCL/PEG nanofibrous scaffold for effective growth inhibition of T47D breast cancer cells. Journal of Drug Delivery Science and Technology., 49, 162–168.
Mellatyar, H., Talaei, S., Pilehvar-Soltanahmadi, Y., Dadashpour, M., Barzegar, A., Akbarzadeh, A., et al. (2018). 17-DMAG-loaded nanofibrous scaffold for effective growth inhibition of lung cancer cells through targeting HSP90 gene expression. Biomedicine & Pharmacotherapy., 105, 1026–1032.
Mondal, D., Griffith, M., & Venkatraman, S. S. (2016). Polycaprolactone-based biomaterials for tissue engineering and drug delivery: Current scenario and challenges. International Journal of Polymeric Materials and Polymeric Biomaterials., 65(5), 255–265.
Sadeghi-Soureh, S., Jafari, R., Gholikhani-Darbroud, R., & Pilehvar-Soltanahmadi, Y. (2020). Potential of Chrysin-loaded PCL/gelatin nanofibers for modulation of macrophage functional polarity towards anti-inflammatory/pro-regenerative phenotype. Journal of Drug Delivery Science and Technology., 58, 101802.
Ahmadi, S., Pilehvar, Y., Zarghami, N., & Abri, A. (2021). Efficient osteoblastic differentiation of human adipose-derived stem cells on TiO2 nanoparticles and metformin co-embedded electrospun composite nanofibers. Journal of Drug Delivery Science and Technology., 66, 102798.
Erdal, N.B., Lando, G.A., Yadav, A., Srivastava, R.K. Hakkarainen, M. (2020) Hydrolytic degradation of porous crosslinked poly (ε-caprolactone) synthesized by high internal phase emulsion templating. Polymers, 12(8), 1849.
Nejati-Koshki, K., Pilehvar-Soltanahmadi, Y., Alizadeh, E., Ebrahimi-Kalan, A., Mortazavi, Y., & Zarghami, N. (2017). Development of Emu oil-loaded PCL/collagen bioactive nanofibers for proliferation and stemness preservation of human adipose-derived stem cells: Possible application in regenerative medicine. Drug development and industrial pharmacy., 43(12), 1978–1988.
Mohandesnezhad, S., Pilehvar-Soltanahmadi, Y., Alizadeh, E., Goodarzi, A., Davaran, S., Khatamian, M., et al. (2020). In vitro evaluation of Zeolite-nHA blended PCL/PLA nanofibers for dental tissue engineering. Materials Chemistry and Physics., 252, 123152.
Yu, D., Thakor, D. K., Han, I., Ropper, A. E., Haragopal, H., Sidman, R. L., et al. (2013). Alleviation of chronic pain following rat spinal cord compression injury with multimodal actions of huperzine A. Proceedings of the National Academy of Sciences., 110(8), E746–E755.
Lograsso, M., Nadeson, R., & Goodchild, C. S. (2002). The spinal antinociceptive effects of cholinergic drugs in rats: Receptor subtype specificity in different nociceptive tests. BMC Pharmacology., 2(1), 1–9.
Mirzaei, H., Shakeri, A., Rashidi, B., Jalili, A., Banikazemi, Z., & Sahebkar, A. (2017). Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies. Biomedicine & Pharmacotherapy., 85, 102–112.
Alibakhshi, A., Ranjbari, J., Pilehvar-Soltanahmadi, Y., Nasiri, M., Mollazade, M., & Zarghami, N. (2016). An update on phytochemicals in molecular target therapy of cancer: Potential inhibitory effect on telomerase activity. Current medicinal chemistry., 23(22), 2380–2393.
Wahlström, B. and Blennow, G. (1978) A study on the fate of curcumin in the rat. Acta pharmacologica et toxicologica, 43, 86–92.
Acknowledgements
The authors would like to thank the “Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran” for their kind cooperation.
Author information
Authors and Affiliations
Contributions
TJ and YH: methodology, investigation, original draft preparation. NE: conceptualization, investigation, resources. AB: investigation, methodology, validation. ATJ: formal analysis, writing–review and editing. MMS: methodology, writing–review and editing. ST: project administration. YP: supervision, writing–review and editing, funding acquisition.
Corresponding author
Ethics declarations
Ethical Approval
All procedures performed in studies involving human participants were under the ethical standards of the Ethics Committee of Tabriz University of Medical Sciences and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Consent to Participate
Not applicable.
Consent to Publish
Not applicable.
Competing Interests
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Tingting Jiang and Yu Han are co-first authors (these authors contributed equally to this work).
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Jiang, T., Han, Y., Esmaeilizadeh, N. et al. Epidural Administration of Curcumin-Loaded Polycaprolactone/Gelatin Electrospun Nanofibers for Extended Analgesia After Laminectomy in Rats. Appl Biochem Biotechnol 195, 6557–6571 (2023). https://doi.org/10.1007/s12010-023-04342-y
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12010-023-04342-y