Skip to main content
Log in

Poly (ε-caprolactone)/poly (N-vinyl-2-pyrrolidone) core–shell nanofibers loaded by multi-walled carbon nanotubes and 5-fluorouracil: an anticancer drug delivery system

  • Materials for life sciences
  • Published:
Journal of Materials Science Aims and scope Submit manuscript

Abstract

Cancer is one of the most fatal diseases in the world. Chemotherapy and radiation therapy are conventional cancer treatments affecting healthy tissues and also have many side effects. Drug delivery systems based on nanofibers can be used as cancer drug carrier with the least side effects. 5FU is one of the most common medicines for many types of cancer. In this study, PCL/PVP core–shell nanofibers containing MWCNTs were performed as 5FU carrier, which was loaded in core of these nanofibers. FESEM images showed all these core–shell nanofibers are uniform and the average diameter was 300–400 nm. There was no interaction between components of nanofibers, and the presence of 5FU in nanofibers was confirmed. The presence of MWCNTs loaded in shell improved the tensile properties. The degradability of nanofibers was investigated, and it was improved by increasing PVP in nanofibers. The morphology change in nanofibers was investigated by FESEM images after degradation. The release behavior of nanofibers was studied. These nanofibers had sustained and prolonged release, and the optimum sample in which 85% of drug released after 528 h was used for cytotoxicity test. The drug release mechanism was modeled by various mathematical models and followed Fick's law. MTT assay on HeLa cell line showed that cell cytotoxicity of 5FU loaded nanofibers was 50.35% after 72 h. The non-toxicity of carrier and efficacy of the drug loaded nanofibers mat on cervical cancer cell line were confirmed. This drug delivery system has the potential to perform as post-surgical anticancer drug delivery system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A (2020) Cancer statistics. CA Cancer J Clin 70(1):7–30

    Article  Google Scholar 

  2. Lewandowska U, Gorlach S, Owczarek K, Hrabec E, Szewczyk K (2014) Synergistic interactions between anticancer chemotherapeutics and phenolic compounds and anticancer synergy between polyphenols. Adv Hyg Exp Med 68

  3. Zhang N, Yin Y, Xu SJ, Chen WS (2008) 5-Fluorouracil: mechanisms of resistance and reversal strategies. Molecules 13(8):1551–1569

    Article  CAS  Google Scholar 

  4. Steichen SD, Caldorera-Moore M, Peppas NA (2013) A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics. Eur J Pharmaceut Sci 48(3):416–427

    Article  CAS  Google Scholar 

  5. Prabaharan M (2015) Chitosan-based nanoparticles for tumor-targeted drug delivery. Int J Biol Macromol 72:1313–1322

    Article  CAS  Google Scholar 

  6. Hu X, Liu S, Zhou G, Huang Y, Xie Z, Jing X (2014) Electrospinning of polymeric nanofibers for drug delivery applications. J Control Release 185:12–21

    Article  CAS  Google Scholar 

  7. Grem JL (2000) 5-Fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development. Investig New Drugs 18(4):299–313

    Article  CAS  Google Scholar 

  8. Rejinold NS, Muthunarayanan M, Chennazhi KP, Nair SV, Jayakumar R (2011) 5-Fluorouracil loaded fibrinogen nanoparticles for cancer drug delivery applications. Int J Biol Macromol 48(1):98–105

    Article  CAS  Google Scholar 

  9. Okuda T, Tominaga K, Kidoaki S (2010) Time-programmed dual release formulation by multilayered drug-loaded nanofiber meshes. J Control Release 143(2):258–264

    Article  CAS  Google Scholar 

  10. Ajnai G, Chiu A, Kan T, Cheng CC, Tsai TH, Chang J (2014) Trends of gold nanoparticle-based drug delivery system in cancer therapy. J Exp Clin Med 6(6):172–178

    Article  CAS  Google Scholar 

  11. Hadjianfar M, Semnani D, Varshosaz J (2018) Polycaprolactone/chitosan blend nanofibers loaded by 5-fluorouracil: An approach to anticancer drug delivery system. Polym Adv Technol 29(12):2972–2981

    Article  CAS  Google Scholar 

  12. Gao Y, Bai Y, Zhao D, Chang MW, Ahmad Z, Li JS (2015) Tuning microparticle porosity during single needle electrospraying synthesis via a non-solvent-based physicochemical approach. Polymers 7(12):2701–2710

    Article  CAS  Google Scholar 

  13. Zamani M, Prabhakaran MP, Ramakrishna S (2013) Advances in drug delivery via electrospun and electrosprayed nanomaterials. Int J Nanomed 8:2997

    Google Scholar 

  14. Torres-Martínez EJ, Cornejo Bravo JM, Serrano Medina A, Pérez González GL, Villarreal Gómez LJ (2018) A summary of electrospun nanofibers as drug delivery system: Drugs loaded and biopolymers used as matrices. Curr Drug Deliv 15(10):1360–1374

    Article  CAS  Google Scholar 

  15. Zeng J, Yang L, Liang Q, Zhang X, Guan H, Xu X, Jing X (2005) Influence of the drug compatibility with polymer solution on the release kinetics of electrospun fiber formulation. J Control Release 105(1–2):43–51

    Article  CAS  Google Scholar 

  16. Absar S, Khan M, Edwards K, Neumann J (2015) Investigation of synthesis and processing of cellulose, cellulose acetate and poly (ethylene oxide) nanofibers incorporating anti-cancer/tumor drug cis-diammineplatinum (II) dichloride using electrospinning techniques. J Polym Eng 35(9):867–878

    Article  CAS  Google Scholar 

  17. Absar S, Khan M, Edwards K, Calamas D (2014) Electrospinning of cisplatin-loaded cellulose nanofibers for cancer drug delivery. In: ASME 2014 international mechanical engineering congress and exposition. American Society of Mechanical Engineers Digital Collection

  18. Martins AF, Vlcek J, Wigmosta T, Hedayati M, Reynolds MM, Popat KC, Kipper MJ (2020) Chitosan/iota-carrageenan and chitosan/pectin polyelectrolyte multilayer scaffolds with antiadhesive and bactericidal properties. Appl Surf Sci 502:144282

    Article  CAS  Google Scholar 

  19. Baker SR, Banerjee S, Bonin K, Guthold M (2016) Determining the mechanical properties of electrospun poly-ε-caprolactone (PCL) nanofibers using AFM and a novel fiber anchoring technique. Mater Sci Eng C 59:203–212

    Article  CAS  Google Scholar 

  20. Niiyama E, Uto K, Ebara M (2019) Electrospun PCL-PCL polyblend nanofibers with high-and low-molecular weight for controlled degradation. Chem Lett 48(7):623–626

    Article  CAS  Google Scholar 

  21. Cheng Z, Teoh SH (2004) Surface modification of ultra thin poly (ε-caprolactone) films using acrylic acid and collagen. Biomaterials 25(11):1991–2001

    Article  CAS  Google Scholar 

  22. Chong EJ, Phan TT, Lim IJ, Zhang YZ, Bay BH, Ramakrishna S, Lim CT (2007) Evaluation of electrospun PCL/gelatin nanofibrous scaffold for wound healing and layered dermal reconstitution. Acta Biomater 3(3):321–330

    Article  CAS  Google Scholar 

  23. Vernosfaderani FR, Semnani D (2018) Manufacturing and optimization the nanofibres tissue of poly (N-vinyl-2-pyrrolidone)-poly (e-caprolactone) shell/poly (N-vinyl-2-pyrrolidone)-amphotericin b core for controlled drug release system. Fibers Polym 19(3):620–626

    Article  CAS  Google Scholar 

  24. Kim GM, Le KHT, Giannitelli SM, Lee YJ, Rainer A, Trombetta M (2013) Electrospinning of PCL/PVP blends for tissue engineering scaffolds. J Mater Sci Mater Med 24(6):1425–1442

    Article  CAS  Google Scholar 

  25. Cruz DMG, Coutinho DF, Mano JF, Ribelles JLG, Sanchez MS (2009) Physical interactions in macroporous scaffolds based on poly (ɛ-caprolactone)/chitosan semi-interpenetrating polymer networks. Polymer 50(9):2058–2064

    Article  CAS  Google Scholar 

  26. Qian W, Yu DG, Li Y, Liao YZ, Wang X, Wang L (2014) Dual drug release electrospun core-shell nanofibers with tunable dose in the second phase. Int J Mol Sci 15(1):774–786

    Article  CAS  Google Scholar 

  27. Saraf A, Baggett LS, Raphael RM, Kasper FK, Mikos AG (2010) Regulated non-viral gene delivery from coaxial electrospun fiber mesh scaffolds. J Controll Release 143(1):95–103

    Article  CAS  Google Scholar 

  28. Lee CH, Hung KC, Hsieh MJ, Chang SH, Juang JH, Hsieh IC, Liu SJ (2020) Core-shell insulin-loaded nanofibrous scaffolds for repairing diabetic wounds. Nanomed Nanotechnol Biol Med 24:102123

    Article  CAS  Google Scholar 

  29. Liao IC, Chen S, Liu JB, Leong KW (2009) Sustained viral gene delivery through core-shell fibers. J Controll Release 139(1):48–55

    Article  CAS  Google Scholar 

  30. Sill TJ, von Recum HA (2008) Electrospinning: applications in drug delivery and tissue engineering. Biomaterials 29(13):1989–2006

    Article  CAS  Google Scholar 

  31. Iqbal S, Rashid MH, Arbab AS, Khan M (2017) Encapsulation of anticancer drugs (5-fluorouracil and paclitaxel) into polycaprolactone (PCL) nanofibers and in vitro testing for sustained and targeted therapy. J Biomed Nanotechnol 13(4):355–366

    Article  CAS  Google Scholar 

  32. Yu H, Yang P, Jia Y, Zhang Y, Ye Q, Zeng S (2016) Regulation of biphasic drug release behavior by graphene oxide in polyvinyl pyrrolidone/poly (ε-caprolactone) core/sheath nanofiber mats. Coll Surf B Biointerfaces 146:63–69

    Article  CAS  Google Scholar 

  33. 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. European Journal of Pharmaceutical Sciences 137:105002

    Article  CAS  Google Scholar 

  34. Kaviannasab E, Semnani D, Khorasani SN, Varshosaz J, Khalili S, Ghahreman F (2019) Core-shell nanofibers of poly (ε–caprolactone) and Polyvinylpyrrolidone for drug delivery system. Mater Res Exp 6(11):115015

    Article  CAS  Google Scholar 

  35. Wang B, Chen X, Ahmad Z, Huang J, Chang MW (2019) 3D electrohydrodynamic printing of highly aligned dual-core graphene composite matrices. Carbon 153:285–297

    Article  CAS  Google Scholar 

  36. Songsurang K, Praphairaksit N, Siraleartmukul K, Muangsin N (2011) Electrospray fabrication of doxorubicin-chitosan-tripolyphosphate nanoparticles for delivery of doxorubicin. Arch Pharm Res 34(4):583

    Article  CAS  Google Scholar 

  37. Gao Y, Zhao D, Chang MW, Ahmad Z, Li X, Suo H, Li JS (2015) Morphology control of electrosprayed core–shell particles via collection media variation. Mater Lett 146:59–64

    Article  CAS  Google Scholar 

  38. Moon SI, Jin F, Lee CJ, Tsutsumi S, Hyon SH (2005) Novel carbon nanotube/poly (l-lactic acid) nanocomposites; their modulus, thermal stability, and electrical conductivity. Macromol Symp Wiley, Weinheim 224(1):287–296

    Article  CAS  Google Scholar 

  39. Elhissi A, Ahmed W, Hassan IU, Dhanak V, D’Emanuele A (2012) Carbon nanotubes in cancer therapy and drug delivery. J Drug Deliv 2012:837327. https://doi.org/10.1155/2012/837327

    Article  CAS  Google Scholar 

  40. Lamastra FR, Puglia D, Monti M, Vella A, Peponi L, Kenny JM, Nanni F (2012) Poly (ε-caprolactone) reinforced with fibres of poly (methyl methacrylate) loaded with multiwall carbon nanotubes or graphene nanoplatelets. Chem Eng J 195:140–148

    Article  CAS  Google Scholar 

  41. Meng ZX, Zheng W, Li L, Zheng YF (2010) Fabrication and characterization of three-dimensional nanofiber membrance of PCL–MWCNTs by electrospinning. Mater Sci Eng C 30(7):1014–1021

    Article  CAS  Google Scholar 

  42. Hadjianfar M, Semnani D, Varshosaz J (2019) An investigation on polycaprolactone/chitosan/Fe3O4 nanofibrous composite used for hyperthermia. Polym Adv Technol 30(11):2729–2741

    Article  CAS  Google Scholar 

  43. ASTM F (2004) 1635–04–standart test method for in vitro degradation testing of hydrolytically degradable polymer resins and fabricated forms for surgical implants. American Society for Testing and Materials International, West Conshohocken, PA

    Google Scholar 

  44. Arifin DY, Lee LY, Wang CH (2006) Mathematical modeling and simulation of drug release from microspheres: Implications to drug delivery systems. Adv Drug Deliv Rev 58(12–13):1274–1325

    Article  CAS  Google Scholar 

  45. Dash S, Murthy PN, Nath L, Chowdhury P (2010) Kinetic modeling on drug release from controlled drug delivery systems. Acta Poloniae Pharmaceutica 67(3):217–23

    CAS  Google Scholar 

  46. Hu J, Zeng F, Wei J, Chen Y, Chen Y (2014) Novel controlled drug delivery system for multiple drugs based on electrospun nanofibers containing nanomicelles. J Biomater Sci Polym Ed 25(3):257–268

    Article  CAS  Google Scholar 

  47. Chiu LCM, Ho TS, Wong EYL, Ooi VE (2006) Ethyl acetate extract of Patrinia scabiosaefolia downregulates anti-apoptotic Bcl-2/Bcl-XL expression, and induces apoptosis in human breast carcinoma MCF-7 cells independent of caspase-9 activation. J Ethnopharmacol 105(1–2):263–268

    Article  Google Scholar 

  48. Berridge MV, Herst PM, Tan AS (2005) Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev 11:127–152

    Article  CAS  Google Scholar 

  49. Huang ZM, Zhang YZ, Ramakrishna S, Lim CT (2004) Electrospinning and mechanical characterization of gelatin nanofibers. Polymer 45(15):5361–5368

    Article  CAS  Google Scholar 

  50. Liu LQ, Tasis D, Prato M, Wagner HD (2007) Tensile mechanics of electrospun multiwalled nanotube/poly (methyl methacrylate) nanofibers. Adv Mater 19(9):1228–1233

    Article  CAS  Google Scholar 

  51. Jeong JS, Moon JS, Jeon SY, Park JH, Alegaonkar PS, Yoo JB (2007) Mechanical properties of electrospun PVA/MWNTs composite nanofibers. Thin Solid Films 515(12):5136–5141

    Article  CAS  Google Scholar 

  52. Moniruzzaman M, Chattopadhyay J, Billups WE, Winey KI (2007) Tuning the mechanical properties of SWNT/nylon 6, 10 composites with flexible spacers at the interface. Nano Lett 7(5):1178–1185

    Article  CAS  Google Scholar 

  53. Yao ZC, Jin LJ, Ahmad Z, Huang J, Chang MW, Li JS (2017) Ganoderma lucidum polysaccharide loaded sodium alginate micro-particles prepared via electrospraying in controlled deposition environments. Int J Pharmaceut 524(1–2):148–158

    Article  CAS  Google Scholar 

  54. Zhou W, Lu P, Sun L, Ji C, Dong J (2012) Diffusion and binding of 5-fluorouracil in non-ionic hydrogels with interpolymer complexation. Int J Pharmaceut 431(1–2):53–60

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dariush Semnani.

Ethics declarations

Conflict of interest

There is no conflict of interest declared.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nasari, M., Semnani, D., Hadjianfar, M. et al. Poly (ε-caprolactone)/poly (N-vinyl-2-pyrrolidone) core–shell nanofibers loaded by multi-walled carbon nanotubes and 5-fluorouracil: an anticancer drug delivery system. J Mater Sci 55, 10185–10201 (2020). https://doi.org/10.1007/s10853-020-04784-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10853-020-04784-3

Navigation