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Hot extrusion of PE/fluorouracil implantable rods for targeted drug delivery in cancer treatment

  • G. V. Salmoria
  • G. B. Ghizoni
  • I. M. Gindri
  • M. S. Marques
  • L. A. Kanis
Original Paper

Abstract

In this study, implantable polyethylene/fluorouracil (PE/FU) rods were manufactured by hot extrusion under different processing conditions. SEM–EDS analyses revealed the effect of temperature on the morphology of the samples. Furthermore, small particles of fluorouracil were observed on the surface and in the PE matrix. Both the FTIR and NIR spectra of the PE/FU rods confirmed the presence of fluorouracil. The PE/FU rods presented lower values of flexural modulus and fatigue resistance than pure PE rods; this was probably due to imperfections and defects introduced into the PE matrix by the fluorouracil particles. The initial amount of FU released by the extruded PE/FU rods (around 35 mg/g) is desirable since it provides a high initial concentration of the drug locally to kill cancer cells following implantation. The subsequent slow and controlled release of the drug (12–45 days) provides suitable levels of the chemotherapeutic agent at the tumor site to improve the anticancer treatment.

Keywords

Polyethylene/fluorouracil Implantable rods Cancer treatment Hot extrusion Properties and drug release 

Notes

Acknowledgements

The authors would like to thank PRONEX/FAPESC, CNPQ and FINEP for financial support and Mr. Paulo C.M. Rosa for the inspiration.

References

  1. 1.
    Weinberg Brent D, Blanco Elvin, Gao Jinming (2008) Polymer implants for intratumoral drug delivery and cancer therapy. J Pharm Sci 97(5):1681–1702CrossRefGoogle Scholar
  2. 2.
    Solorio L, Patel RB, Wu H, Krupka T, Exner AA (2010) Advances in image-guided intratumoral drug delivery techniques. Ther Deliv 1(2):307–322CrossRefGoogle Scholar
  3. 3.
    Olivi A, Ewend MG, Utsuki T, Tyler B, Domb AJ, Brat DJ, Brem H (1996) Interstitial delivery of carboplatin via biodegradable Polymers is effective against experimental glioma in the rat. Cancer Chemother Pharmacol 39:90–96CrossRefGoogle Scholar
  4. 4.
    Zhang Pei, Zhang Huiyuan, He Wenxiu, Zhao Dujuan, Song Aixin, Luan Yuxia (2016) Disulfide-linked amphiphilic polymer-docetaxel conjugates assembled redox-sensitive micelles for efficient antitumor drug delivery. Biomacromolecules 17:1621–1632CrossRefGoogle Scholar
  5. 5.
    Shia C, Zhang Z, Shia J, Wangb F, Luana Y (2015) Co-delivery of docetaxel and chloroquine via PEO–PPO–PCL/TPGS micelles for overcoming multidrug resistance. Int J Pharm 495:932–939CrossRefGoogle Scholar
  6. 6.
    Weinberg BD, Ai H, Blanco E, Anderson JM, Gao J (2007) Antitumor efficacy and local distribution of doxorubicin via intratumoral delivery from polymer millirods. J Biomed Mater Res 81A:161–170.  https://doi.org/10.1002/jbm.a.30914 CrossRefGoogle Scholar
  7. 7.
    Seno Hiroshi, Ito Kazuki, Kojima Koichi, Nakajima Nobuaki, Chiba Tsutomu (1999) Efficacy of an implanted drug delivery system for advanced hepatocellular carcinoma using 5-fluorouracil, epirubicin and mitomycin C. J Gastroenterol Hepatol 14:811–816CrossRefGoogle Scholar
  8. 8.
    Wang Shenguo, Chen Hongli, Cai Qing, Bei Jianzhong (2001) Degradation and 5-fluorouracil release behavior in vitro of polyethylene/poly(ethylene oxide)/polylactide tri-component copolymer. Polym Adv Technol 12:253–258CrossRefGoogle Scholar
  9. 9.
    Martini LG, Collett JH, Attwood D (2000) The release of 5-fluorouracil from microspheres of poly(epsiloncaprolactone-co-ethylene oxide). Drug Dev Ind Pharm 26(1):7–12CrossRefGoogle Scholar
  10. 10.
    Shah S, Maddineni S, Lu J, Repka MA (2013) Melt extrusion with poorly soluble drugs. Int J Pharm 453:233–252CrossRefGoogle Scholar
  11. 11.
    Maniruzzaman M, Boateng JS, Snowden MJ, Douroumis D (2013) A review of hot-meltextrusion: process technology to pharmaceutical products. Int Sch Res Netw ISRN Pharm 2012, Article ID 436763, 9 pages  https://doi.org/10.5402/2012/436763
  12. 12.
    Forster A, Hempenstall J, Tucker I, Rades T (2001) Selection of excipients for melt extrusion with two poorly water-soluble drugs by solubility parameter calculation and thermal analysis. Int J Pharm 226:147–161CrossRefGoogle Scholar
  13. 13.
    Santos DV, Casadei APM, Pereira RV, Aragones A, Salmoria GV, Fredel MC (2012) Development of polymer/nanoceramic composite material with potential application in biomedical engineering. Mater Sci Forum 727:1142–1146CrossRefGoogle Scholar
  14. 14.
    Crowley MM, Fredersdorf A, Schroeder B, Kucer S, Prodduturi S, Repka MA, McGinity JW (2004) The influence of guaifenesin and ketoprofen on the properties of hot-melt extruded polyethylene oxide films. Eur J Pharm Biopharm 22:409–418Google Scholar
  15. 15.
    Crowley MM, Schroeder B, Fredersdorf A, Obara S, Talarico M, Kucera S, McGinity JW (2004) Physicochemical properties and mechanism of drug release from ethyl cellulose matrix tablets prepared by direct compression and hot-melt extrusion. Int J Pharm 269:509–522CrossRefGoogle Scholar
  16. 16.
    Zepon KM, Vieira LF, Soldi V, Salmoria GV, Kanis LA (2013) Influence of process parameters on microstructure and mechanical properties of starch-cellulose acetate/silver sulfadiazine matrices prepared by melt extrusion. Polym Test 32:1123–1127CrossRefGoogle Scholar
  17. 17.
    Zepon KM, Petronilho F, Soldi V, Salmoria GV, Kanis LA (2014) Production and characterization of cornstarch/cellulose acetate/silver sulfadiazine extrudate matrices. Mater Sci Eng C 44:225–233CrossRefGoogle Scholar
  18. 18.
    Guo G, Fu SZ, Zhou LX, Liang H, Fan M, Luo F, Qian ZY, Wei YQ (2011) Preparation of curcumin loaded poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) nanofibers and their in vitro antitumor activity against Glioma 9L cells. Nanoscale 3:3825–3832CrossRefGoogle Scholar
  19. 19.
    Yilmaz M, Vayvada H, Aydın E, Menderes A, Atabey A (2007) Repair of fractures of the orbital floor with porous polyethylene implants. Br J Oral Maxillofac Surg 45(8):640–644CrossRefGoogle Scholar
  20. 20.
    Singh P, Tyagi G, Mehrotra R, Bakhshi AK (2009) Thermal stability studies of 5-fluorouracil using diffuse reflectance infrared spectroscopy. Drug Test Anal 1:240–244CrossRefGoogle Scholar
  21. 21.
    Gulmine V, Janissek PR, Heise HM, Akcelrud L (2002) Polyethylene characterization by FTIR. Polym Test 21:557–563.  https://doi.org/10.1016/S0142-9418(01)00124-6 CrossRefGoogle Scholar
  22. 22.
    Peacock AJ (2000) Handbook of polyethylene: structures, properties, and applications. Marcel Dekker, New YorkGoogle Scholar
  23. 23.
    Edward SK, Mahpour M (1973) The identification and origin of N–H overtone and combination bands in the near-infrared spectra of simple primary and secondary amides. Spectrochim Acta A 29:1233–1246CrossRefGoogle Scholar
  24. 24.
    Hazen KH, Arnold MA, Small GW (1998) Measurement of glucose in water with first-overtone near-infrared spectra. Appl Spectrosc 52:1597–1605CrossRefGoogle Scholar
  25. 25.
    Eddy Christopher V, Arnold Mark A (2001) Near-infrared spectroscopy for measuring urea in hemodialysis fluids. Clin Chem 47(7):1279–1286Google Scholar
  26. 26.
    Crandall EW, Jagtap AN (1977) The near-infrared spectra of polymers. J Appl Polym Sci 21:449–454.  https://doi.org/10.1002/app.1977.070210211 CrossRefGoogle Scholar
  27. 27.
    Mirabella FM, Bafna A (2002) Determination of the crystallinity of polyethylene/α-olefin copolymers by thermal analysis: relationship of the heat of fusion of 100% polyethylene crystal and the density. J Polym Sci B Polym Phys 40:1637–1643CrossRefGoogle Scholar
  28. 28.
    Yassin AEB, Anwer MK, Mowafy HA, El-Bagory IM, Bayomi MA, Alsarra IA (2010) Optimization of 5-fluorouracil solid-lipid nanoparticles: a preliminary study to treat colon cancer. Int J Med Sci 7(6):398–408.  https://doi.org/10.7150/ijms.7.398 CrossRefGoogle Scholar
  29. 29.
    Lee JS, Chae GS, An TK, Khang G, Cho SH, Lee HB (2003) Preparation of 5-fluorouracil-loaded poly(L-lactide-co-glycolide) wafer and evaluation of in vitro release behavior. Macromol Res 11(3):183–188CrossRefGoogle Scholar
  30. 30.
    Hanafy AFAH, El-Egaky AM, Mortada SAM, Molokhia AM (2009) Development of implants for sustained release of 5-fluorouracil using low molecular weight biodegradable polymers. Drug Discov Ther 3(6):287–295Google Scholar
  31. 31.
    Sairam M, Babu VR, Naidu BVK, Aminabhavi TM (2006) Encapsulation efficiency and controlled release characteristics of crosslinked polyacrylamide particles. Int J Pharm 320:131–136CrossRefGoogle Scholar
  32. 32.
    Gao H, Gu Y, Ping Q (2007) The implantable 5-fluorouracil-loaded poly(l-lactic acid) fibers prepared by wet-spinning from suspension. J Controll Release 3(23):325–332CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • G. V. Salmoria
    • 1
    • 2
  • G. B. Ghizoni
    • 1
  • I. M. Gindri
    • 2
  • M. S. Marques
    • 3
  • L. A. Kanis
    • 3
  1. 1.NIMMA, Department of Mechanical EngineeringFederal University of Santa CatarinaFlorianópolisBrazil
  2. 2.Biomechanics Engineering Laboratory, University Hospital (HU)Federal University of Santa CatarinaFlorianópolisBrazil
  3. 3.Grupo de Desenvolvimento em Tecnologia FarmacêuticaUniversidade do Sul de Santa CatarinaTubarãoBrazil

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