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Tri-layered Polycaprolactone/Taxol/Gelatin/5-FU Nanofibers Against MCF-7 Breast Cancer Cells

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Abstract

Nanofibers prepared by the electrospinning process are good candidates for the local delivery of anticancer drugs. In the present study, 5-Fluorouracil (5-FU) and Paclitaxel (Taxol) anticancer drugs were loaded into the mono and tri-layered polycaprolactone (PCL)/gelatin (Gel) electrospun nanofibers. The performance of nanofibers was investigated for the controlled release of anticancer drugs against MCF-7 breast cancer cell death. The drug loading efficiency of Taxol and 5-FU from tri-layered nanofiber samples (PCL/Gel–PCL/Taxol /Gel/5-FU–PCL/Gel nanofibers) was 97 and 98%, respectively. These amounts for mono-layered nanofibers (PCL/Taxol and Gel/5-FU nanofibers) were 85 and 87% for Taxol and 5-FU, respectively. The controlled release of anti-cancer drugs from mono- and tri-layered nanofibers containing 1.5 mg Taxol and 1.5 mg 5-FU was obtained within 36 and 72 h, respectively. By increasing the content of Taxol and 5-FU to 3.0 mg in tri-layered nanofibers, the controlled release time was decreased to 60 h. 5-FU and Taxol release data were best described using the Korsmeyer–peppas model pharmacokinetic model. More than 98% of L929 fibroblast cells survived in the presence of the PCL/Gel nanofibers, which indicated good biocompatibility of the nanofibers. The maximum cytotoxicity of tri-layered PCL/Taxol /Gel/5-FU nanofibers containing 3 mg 5-FU and 3 mg Taxol was 75 ± 3% against MCF-7 breast cancer cells after 72 h. The results showed that tri-layered nanofibers are a more efficient carrier for drug loading and treatment of MCF-7 breast cancer cells than mono-layered nanofibers.

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References

  1. Peng CL, Lai PS, Lin FH, Wu SY, Shieh MJ (2009) Dual chemotherapy and photodynamic therapy in an HT-29 human colon cancer xenograft model using SN-38-loaded chlorin-core star block copolymer micelles. Biomaterials 30:3614–3625

    Article  CAS  PubMed  Google Scholar 

  2. Wei L, Cai C, Lin J, Chen T (2009) Dual-drug delivery system based on hydrogel/micelle composites. Biomaterials 30:2606–2613

    Article  CAS  PubMed  Google Scholar 

  3. Sipos B, Budai-Szűcs M, Kókai D, Orosz L, Burián K, Csorba A, Nagy ZZ, Balogh GT, Csóka I, Katona G (2022) Erythromycin-loaded polymeric micelles: in situ gel development, in vitro and ex vivo ocular investigations. Europ J Pharm Biopharm 180:81–90. https://doi.org/10.1016/j.ejpb.2022.09.023

    Article  CAS  Google Scholar 

  4. Kang R, Song M, Fang Z, Liu K (2022) Nano-composite hydrogels of Cu-Apa micelles for anti-vasculogenic mimicry. J Drug Target 19:1–3. https://doi.org/10.1080/1061186X.2022.2115047

    Article  Google Scholar 

  5. Konishi M, Tabata Y, Kariya M, Hosseinkhani H, Suzuki A, Fukuhara K, Mandai M, Takakura K, Fujii S (2005) In vivo anti-tumor effect of dual release of cisplatin and adriamycin from biodegradable gelatin hydrogel. J Control Release 103:7–19

    Article  CAS  PubMed  Google Scholar 

  6. Norouzi M, Nazari B, Miller DW (2016) Injectable hydrogel-based drug delivery systems for local cancer therapy. Drug Discovery Today 21:1835–1849

    Article  CAS  PubMed  Google Scholar 

  7. Pakian S, Radmanesh F, Sadeghi-Abandansari H, Nabid MR (2022) Gelatin-based Injectable hydrogel/microgel composite as a combinational dual drug delivery system for local co-delivery of curcumin and 5-fluorouracil in synergistic therapy of colorectal cancer. ACS Appl Polym Mater 4:8238–8252

    Article  CAS  Google Scholar 

  8. Chen X, Zhu Q, Liu Z, Zhang T, Gong C, Li J, Yan H, Lin Q (2023) Self-aggregate performance of hexyl alginate ester derivative synthesized via SN2 reaction for controlled release of λ-cyhalothrin. Polym Bull 80:495–514

    Article  CAS  Google Scholar 

  9. Men W, Zhu P, Dong S, Liu W, Zhou K, Bai Y, Liu X, Gong S, Zhang S (2020) Layer-by-layer pH-sensitive nanoparticles for drug delivery and controlled release with improved therapeutic efficacy in vivo. Drug Deliv 27:180–190. https://doi.org/10.1080/10717544.2019.1709922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tabakoglu S, Kołbuk D, Sajkiewicz P (2023) Multifluid electrospinning for multi-drug delivery systems: pros and cons, challenges, and future directions. Biomater Sci 11:37–61

    Article  CAS  Google Scholar 

  11. Immich AP, Arias ML, Carreras N, Boemo RL, Tornero JA (2013) Drug delivery systems using sandwich configurations of electrospun poly (lactic acid) nanofiber membranes and ibuprofen. Mater Sci Eng C 33:4002–4008

    Article  CAS  Google Scholar 

  12. Okuda T, Tominaga K, Kidoaki S (2010) Time-programmed dual release formulation by multilayered drug-loaded nanofiber meshes. J Control Release 143:258–264

    Article  CAS  PubMed  Google Scholar 

  13. Robles-Martinez P, Xu X, Trenfield SJ, Awad A, Goyanes A, Telford R, Basit AW, Gaisford S (2019) 3D printing of a multi-layered polypill containing six drugs using a novel stereolithographic method. Pharmaceutics 11:274. https://doi.org/10.3390/pharmaceutics11060274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Castellano JM, Sanz G, Peñalvo JL, Bansilal S, Fernández-Ortiz A, Alvarez L, Guzmán L, Linares JC, García F, D’Aniello F, Arnáiz JA (2014) A polypill strategy to improve adherence: results from the FOCUS project. J Am Coll Cardiol 64:2071–2082

    Article  PubMed  Google Scholar 

  15. Pereira BC, Isreb A, Forbes RT, Dores F, Habashy R, Petit J-B, Alhnan MA, Oga EF (2019) Temporary plasticiser’: a novel solution to fabricate 3D printed patient-centred cardiovascular ‘polypill’ architectures. Eur J Pharm Biopharm 135:94–103

    Article  CAS  PubMed  Google Scholar 

  16. Sadia M, Isreb A, Abbadi I, Isreb M, Aziz D, Selo A, Timmins P, Alhnan MA (2018) From ‘fixed dose combinations’ to ‘a dynamic dose combiner’: 3D printed bi-layer antihypertensive tablets. Eur J Pharm Sci 123:484–494

    Article  CAS  PubMed  Google Scholar 

  17. Mašek J, Lubasova D, Lukáč R, Turanek-Knotigova P, Kulich P, Plockova J, Mašková E, Prochazka L, Koudelka Å, Sasithorn N, Gombos J (2017) Multi-layered nanofibrous mucoadhesive films for buccal and sublingual administration of drug-delivery and vaccination nanoparticles-important step towards effective mucosal vaccines. J Control Release 249:183–195. https://doi.org/10.1016/j.jconrel.2016.07.036

    Article  CAS  PubMed  Google Scholar 

  18. Panigrahi G, Medhi H, Wasnik K, Patra S, Gupta P, Pareek D, Maity S, Mandey M, Paik P (2022) Hollow mesoporous SiO2–ZnO nanocapsules and effective in vitro delivery of anticancer drugs against different cancers with low doses of drugs. Mater Chem Phys 287:126287. https://doi.org/10.1016/j.matchemphys.2022.126287

    Article  CAS  Google Scholar 

  19. Trushina DB, Sapach AY, Burachevskaia OA, Medvedev PV, Khmelenin DN, Borodina TN, Soldatov MA, Butova VV (2022) Doxorubicin-loaded core–shell UiO-66@ SiO2 metal–organic frameworks for targeted cellular uptake and cancer treatment. Pharmaceutics 14:1325. https://doi.org/10.3390/pharmaceutics14071325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kazmi I, Al-Abbasi Fahad A, Imam Syed Sarim, Afzal Muhammad, Nadeem Muhammad Shahid, Altayb Hisham N, Alshehri Sultan (2022) Formulation of piperine nanoparticles: in vitro breast cancer cell line and in vivo evaluation. Polymers 14(7):1349. https://doi.org/10.3390/polym14071349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sabzini M, Pourmadadi M, Yazdian F, Khadiv-Parsi P, Rashedi H (2023) Development of chitosan/halloysite/graphiticcarbon nitride nanovehicle for targeted delivery of quercetin to enhance its limitation in cancer therapy: an in vitro cytotoxicity against MCF-7 cells. Int J Biol Macromol 226:159–171. https://doi.org/10.1016/j.ijbiomac.2022.11.189

    Article  CAS  PubMed  Google Scholar 

  22. Nouri A, Faraji Dizaji B, Kianinejad N, Jafari Rad A, Rahimi S, Irani M, Sharifian Jazi F (2021) Simultaneous linear release of folic acid and doxorubicin from ethyl cellulose/chitosan/g-C3N4/MoS2 core‐shell nanofibers and its anticancer properties. J Biomed Mater Res A 109:903–914

    Article  CAS  PubMed  Google Scholar 

  23. Yadav D, Semwal BC, Dewangan HK (2022) Grafting, characterization and enhancement of therapeutic activity of berberine loaded PEGylated PAMAM dendrimer for cancerous cell. J Biomater Sci Polym Ed. https://doi.org/10.1080/09205063.2022.2155782

    Article  PubMed  Google Scholar 

  24. Talimi R, Shahsavari Z, Dadashzadeh S, Ten Hagen TL, Haeri A (2022) Sirolimus-exuding core-shell nanofibers as an implantable carrier for breast cancer therapy: Preparation, characterization, in vitro cell studies, and in vivo anti-tumor activity. Drug Dev Ind Pharm. https://doi.org/10.1080/03639045.2022.2161559

    Article  PubMed  Google Scholar 

  25. Suárez DF, Pinzón-García AD, Sinisterra RD, Dussan A, Mesa F, Ramírez-Clavijo S (2022) Uniaxial and Coaxial Nanofibers PCL/Alginate or PCL/Gelatine transport and release tamoxifen and curcumin affecting the viability of MCF7 cell line. Nanomaterials 12:3348. https://doi.org/10.3390/nano12193348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bahmani E, Dizaji BF, Talaei S, Koushkbaghi S, Yazdani H, Abadi PG, Akrami M, Shahrousvand M, Jazi FS, Irani M (2023) Fabrication of poly (ϵ-caprolactone)/paclitaxel (core)/chitosan/zein/multi‐walled carbon nanotubes/doxorubicin (shell) nanofibers against MCF‐7 breast cancer. Polym Adv Technol 34:789–799. https://doi.org/10.1002/pat.5931

    Article  CAS  Google Scholar 

  27. Amini Z, Rudsary SS, Shahraeini SS, Dizaji BF, Goleij P, Bakhtiari A, Irani M, Sharifianjazi F (2021) Magnetic bioactive glasses/cisplatin loaded-chitosan (CS)-grafted-poly (ε-caprolactone) nanofibers against bone cancer treatment. Carbohyd Polym 258:117680. https://doi.org/10.1002/pat.5931

    Article  CAS  Google Scholar 

  28. Son YJ, Kim WJ, Yoo HS (2014) Therapeutic applications of electrospun nanofibers for drug delivery systems. Arch Pharm Res 37:69–78. https://doi.org/10.1007/s12272-013-0284-2

    Article  CAS  PubMed  Google Scholar 

  29. Goyal R, Macri LK, Kaplan HM, Kohn J (2016) Nanoparticles and nanofibers for topical drug delivery. J Controlled Release 240:77–92. https://doi.org/10.1016/j.jconrel.2015.10.049

    Article  CAS  Google Scholar 

  30. Ghafoor B, Aleem A, Ali MN, Mir M (2018) Review of the fabrication techniques and applications of polymeric electrospun nanofibers for drug delivery systems. J Drug Deliv Sci Technol 48:82–87. https://doi.org/10.1016/j.jddst.2018.09.005

    Article  CAS  Google Scholar 

  31. Abdul Hameed MM, Mohamed Khan SA, Thamer BM, Rajkumar N, El-Hamshary H, El‐Newehy M (2023) Electrospun nanofibers for drug delivery applications: methods and mechanism. Polym Adv Technol 34:6–23. https://doi.org/10.1002/pat.5884

    Article  CAS  Google Scholar 

  32. Iurciuc-Tincu CE, Cretan MS, Purcar V, Popa M, Daraba OM, Atanase LI, Ochiuz L (2020) Drug delivery system based on pH-sensitive biocompatible poly (2-vinyl pyridine)-b-poly (ethylene oxide) nanomicelles loaded with curcumin and 5-fluorouracil. Polymers 12:1450. https://doi.org/10.3390/polym12071450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Dash S, Murthy PN, Nath L, Chowdhury P (2010) Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 67:217–223

    CAS  PubMed  Google Scholar 

  34. Jäger W, Gruber A, Giessrigl B, Krupitza G, Szekeres T, Sonntag D (2011) Metabolomic analysis of resveratrol-induced effects in the human breast cancer cell lines MCF-7 and MDA-MB-231. OMICS J Integr Biol 15:9–14. https://doi.org/10.1089/omi.2010.0114

    Article  CAS  Google Scholar 

  35. Pourbaferani M, Modiri S, Norouzy A, Maleki H, Heidari M, Alidoust L, Derakhshan V, Zahiri HS, Noghabi KA (2021) A newly characterized potentially probiotic strain, Lactobacillus brevis MK05, and the toxicity effects of its secretory proteins against MCF-7 breast cancer cells. Probiotics Antimicrob Proteins 13:982–992. https://doi.org/10.1007/s12602-021-09766-8

    Article  CAS  PubMed  Google Scholar 

  36. Ajabnoor GM, Crook T, Coley HM (2012) Paclitaxel resistance is associated with switch from apoptotic to autophagic cell death in MCF-7 breast cancer cells. Cell Death Dis 3:e260. https://doi.org/10.1038/cddis.2011.139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Almafie MR, Marlina L, Riyanto R, Jauhari J, Nawawi Z, Sriyanti I (2022) Dielectric properties and flexibility of polyacrylonitrile/graphene oxide composite nanofibers. ACS Omega 7:33087–33096. https://doi.org/10.1021/acsomega.2c03144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Razali NA, Lin WC (2022) Accelerating the excisional wound closure by using the patterned microstructural nanofibrous mats/gentamicin-loaded hydrogel composite scaffold. Mater Today Bio 16:100347. https://doi.org/10.1016/j.mtbio.2022.100347

    Article  CAS  Google Scholar 

  39. Sohrabi A, Shaibani PM, Etayash H et al (2013) Sustained drug release and antibacterial activity of ampicillin incorporated poly(methyl methacrylate)–nylon6 core/shell nanofibers. Polymer 54:2699–2705

    Article  CAS  Google Scholar 

  40. Gautam S, Sharma C, Purohit SD, Singh H, Dinda AK, Potdar PD, Chou CF, Mishra NC (2021) Gelatin-polycaprolactone-nanohydroxyapatite electrospun nanocomposite scaffold for bone tissue engineering. Mater Sci Eng C 119: 111588

    Article  CAS  Google Scholar 

  41. Ghahreman F, Semnani D, Khorasani SN, Varshosaz J, Khalili S, Mohammadi S, Kaviannasab E (2020) Polycaprolactone–gelatin membranes in controlled drug delivery of 5-Fluorouracil. Polym Sci - A 62:636–647

    Article  Google Scholar 

  42. Aydin RS, Pulat M (2012) 5-Fluorouracil encapsulated chitosan nanoparticles for pH-stimulated drug delivery: evaluation of controlled release kinetics. J Nanomater 2012:42

    Google Scholar 

  43. Ha PT, Nguyen HN, Do HD, Phan QT, Thi MN, Nguyen XP, Thi MN, Le MH, Nguyen LT, Bui TQ (2016) Targeted drug delivery nanosystems based on copolymer poly (lactide)-tocopheryl polyethylene glycol succinate for cancer treatment. Adv Nat Sci Nanosci Nanotechnol 7:015001

    Article  ADS  Google Scholar 

  44. Laha A, Sharma CS, Majumdar S (2017) Sustained drug release from multi-layered sequentially crosslinked electrospun gelatin nanofiber mesh. Mater Sci Eng C 76:782–786. https://doi.org/10.1016/j.msec.2017.03.110

    Article  CAS  Google Scholar 

  45. Esfahani RE, Zahedi P, Zarghami R (2021) 5-Fluorouracil-loaded poly (vinyl alcohol)/chitosan blend nanofibers: morphology, drug release and cell culture studies. Iran Polym J 30:167–177. https://doi.org/10.1007/s13726-020-00882-w

    Article  CAS  Google Scholar 

  46. Zhu LF, Zheng Y, Fan J, Yao Y, Ahmad Z, Chang MW (2019) A novel core-shell nanofiber drug delivery system intended for the synergistic treatment of melanoma. Europ J Pharm Sci 137:105002. https://doi.org/10.1016/j.ejps.2019.105002

    Article  CAS  Google Scholar 

  47. Zhang J, Li J, Xu C, ** Z, Ren Y, Song Q, Lu S (2020) Novel pH-sensitive drug-loaded electrospun nanofibers based on regenerated keratin for local tumor chemotherapy. Text Res J 90:2336–2349. https://doi.org/10.1177/0040517520919

    Article  CAS  Google Scholar 

  48. Poursharifi N, Semnani D, Soltani P, Amanpour S (2020) Designing a novel and versatile multi-layered nanofibrous structure loaded with MTX and 5-FU for the targeted delivery of anticancer drugs. Polym Degrad Stab 179:109275. https://doi.org/10.1016/j.polymdegradstab.2020.109275

    Article  CAS  Google Scholar 

  49. Ma G, Liu Y, Peng C, Fang D, He B, Nie J (2011) Paclitaxel loaded electrospun porous nanofibers as mat potential application for chemotherapy against prostate cancer. Carbohydr Polym 86:505–512. https://doi.org/10.1016/j.carbpol.2011.04.082

    Article  CAS  Google Scholar 

  50. Hasanbegloo K, Banihashem S, Dizaji BF, Bybordi S, Farrokh-Eslamlou N, Abadi PG, Jazi FS, Irani M (2023) Paclitaxel-loaded liposome-incorporated chitosan (core)/poly (ε-caprolactone)/chitosan (shell) nanofibers for the treatment of breast cancer. Int J Biol Macromol 230:123380. https://doi.org/10.1016/j.ijbiomac.2023.123380

    Article  CAS  PubMed  Google Scholar 

  51. Abasalta M, Asefnejad A, Khorasani MT, Saadatabadi AR, Irani M (2022) Adsorption and sustained release of doxorubicin from N-carboxymethyl chitosan/polyvinyl alcohol/poly (ε-caprolactone) composite and core-shell nanofibers. J Drug Deliv Sci Technol 67:102937

    Article  CAS  Google Scholar 

  52. Darbasizadeh B, Mortazavi SA, Kobarfard F, Jaafari MR, Hashemi A, Farhadnejad H, Feyzibarnaji B (2021) Electrospun Doxorubicin-loaded PEO/PCL core/sheath nanofibers for chemopreventive action against breast cancer cells. J Drug Deliv Sci Technol 64:102576

    Article  CAS  Google Scholar 

  53. Farboudi A, Mahboobnia K, Chogan F, Karimi M, Askari A, Banihashem S, Davaran S, Irani M (2020) UiO-66 metal organic framework nanoparticles loaded carboxymethyl chitosan/poly ethylene oxide/polyurethane core-shell nanofibers for controlled release of doxorubicin and folic acid. Int J Biol Macromol 150:178–188

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was financially supported by the Alborz University of Medical Sciences and Islamic Azad University, Science and Research Brach.

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  1. Faculty of Medical Sciences and Technologies, Department of Biomedical Engineering, Science and Research Brach, Islamic Azad University, Tehran, Iran

    Shaghayegh Takmilsefat Najjari, Azadeh Asefnejad & Nahid Hasnzadeh Nemati

  2. Department of Pharmaceutics, School of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran

    Parvaneh Ghaderi Shikhi Abadi & Mohammad Irani

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SN: methodology AA: idea and revision PA: writing of manuscript NN: calculation MI: idea and editing.

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Najjari, S.T., Asefnejad, A., Abadi, P.G.S. et al. Tri-layered Polycaprolactone/Taxol/Gelatin/5-FU Nanofibers Against MCF-7 Breast Cancer Cells. J Polym Environ 32, 791–802 (2024). https://doi.org/10.1007/s10924-023-02970-3

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