Abstract
The ethylene vinyl acetate copolymer (EVA)/Poly (lactic acid) (PLA) blend and EVA/Poly (ethylene glycol) (PEG) blend were applied as the drug carrier materials for a bi-layer drug-loaded stent coating film, which consisted of a paclitaxel (PTX)-loaded layer and a drug-free EVA layer. The changes of weight and appearance of the drug-free polymeric blend films with increasing time were examined by X-ray diffraction analysis (XRD), gel permeation chromatography (GPC) tests and scanning electronic microscopy (SEM), and the results showed the degradation of PLA and the leaching of PEG from the films. The effects of PLA, PEG and drug contents on in vitro drug release were investigated, and the results demonstrated that the addition of PLA promoted the drug release while the addition of PEG almost did not. Franz cells diffusion test results indicated that the bi-layer structure successfully endowed the stent coating with the release of drug in a unidirectional fashion. The release profiles of films incorporated PTX and the mechanical performance of the film could be customized by readily adjusting the contents of the blend components. Therefore, the polymeric blends could be useful drug carrier materials for drug-loaded stent coating capable of releasing drug in a highly tunable manner.
Similar content being viewed by others
References
Lei L, Liu X, Guo S, Tang M, Cheng L, Tian L. 5-fluorouracil-loaded multilayered films for drug controlled releasing stent application: drug release, microstructure, and ex vivo permeation behaviors. J Control Release. 2010;146(1):45–53. doi:10.1016/j.jconrel.2010.05.017.
Kolachalama VB, Tzafriri AR, Arifin DY, Edelman ER. Luminal flow patterns dictate arterial drug deposition in stent-based delivery. J Control Release. 2009;133(1):24–30. doi:10.1016/j.jconrel.2008.09.075.
Guildford A, Colombo P, Bruschi G, Bonacina E, Klugmann S, Santin M. Direct comparison of the short-term clinical performance of z guidant and taxus stents. Int J Cardiol. In Press. doi:10.1016/j.ijcard.2008.12.161.
Grube E, Silber S, Hauptmann KE, Mueller R, Buellesfeld L, Gerckens U, et al. Six- and twelve-month results from a randomized, double-blind trial on a slow-release paclitaxel-eluting stent for de novo coronary lesions. Circulation. 2003;107(1):38–42. doi:10.1161/01.cir.0000047700.58683.a1.
Unger F, Westedt U, Hanefeld P, Wombacher R, Zimmermann S, Greiner A, et al. Poly(ethylene carbonate): a thermoelastic and biodegradable biomaterial for drug eluting stent coatings? J Control Release. 2007;117(3):312–21. doi:10.1016/j.jconrel.2006.11.003.
Pan CJ, Tang JJ, Weng YJ, Wang J, Huang N. Preparation and characterization of rapamycin-loaded plga coating stent. J Mater Sci Mater Med. 2007;18(11):2193–8. doi:10.1007/s10856-007-3075-9.
Perin EC. Choosing a drug-eluting stent: a comparison between cypher and taxus. Rev Cardiovasc Med. 2005;6(Suppl 1):S13–21.
Xu ZH, Gu WW, Huang J, Sui H, Zhou ZH, Yang YX, et al. In vitro and in vivo evaluation of actively targetable nanoparticles for paclitaxel delivery. Int J Pharm. 2005;288(2):361–8. doi:10.1016/j.ijpharm.2004.10.009.
Shi RW, Burt HM. Amphiphilic dextran-graft-poly(epsilon-caprolactone) films for the controlled release of paclitaxel. Int J Pharm. 2004;271(1–2):167–79. doi:10.1016/j.ijpharm.2003.11.005.
Suh HR, Jeong BM, Rathi R, Kim SW. Regulation of smooth muscle cell proliferation using paclitaxel-loaded poly(ethylene oxide)-poly(lactide/glycolide) nanospheres. J Biomed Mater Res. 1998;42(2):331–8.
Drachman DE, Edelman ER, Seifert P, Groothuis AR, Bornstein DA, Kamath KR, et al. Neointimal thickening after stent delivery of paclitaxel: change in composition and arrest of growth over six months. J Am Coll Cardiol. 2000;36(7):2325–32.
Jackson JK, Skinner KC, Burgess L, Sun T, Hunter WL, Burt HM. Paclitaxel-loaded crosslinked hyaluronic acid films for the prevention of postsurgical adhesions. Pharm Res. 2002;19(4):411–7.
Kalachandra S, Lin DM, Stejskal EO, Prakki A, Offenbacher S. Drug release from cast films of ethylene vinyl acetate (eva) copolymer: stability of drugs by h-1 nmr and solid state c-13 cp/mas nmr. J Mater Sci Mater Med. 2005;16(7):597–605.
Costantini LC, Kleppner SR, McDonough J, Azar MR, Patel R. Implantable technology for long-term delivery of nalmefene for treatment of alcoholism. Int J Pharm. 2004;283(1–2):35–44. doi:10.1016/j.ijpharm.2004.05.034.
Guo Q, Guo S, Wang Z. A type of esophageal stent coating composed of one 5-fluorouracil-containing eva layer and one drug-free protective layer: In vitro release, permeation and mechanical properties. J Control Release. 2007;118(3):318–24. doi:10.1016/j.jconrel.2006.12.030.
Ramadevi A, Padmavathy T, Stigall G, Paquette D, Kalachandra S. Eva copolymer matrix for intra-oral delivery of antimicrobial and antiviral agents. J Mater Sci Mater Med. 2008;19(2):721–7. doi:10.1007/s10856-007-3109-3.
Kalachandra S, Lin DM, Offenbacher S. Controlled drug release for oral condition by a novel device based on ethylene vinyl acetate (eva) copolymer. J Mater Sci Mater Med. 2002;13(1):53–8.
Cho CW, Choi JS, Shin SC. Physicochemical characteristics of quinupramine in the eva matrix. Int J Pharm. 2006;320(1–2):1–3. doi:10.1016/j.ijpharm.2006.06.016.
Moly KA, Radusch HJ, Androsh R, Bhagawan SS, Thomas S. Nonisothermal crystallisation, melting behavior and wide angle x-ray scattering investigations on linear low density polyethylene (lldpe)/ethylene vinyl acetate (eva) blends: effects of compatibilisation and dynamic crosslinking. Eur Polym J. 2005;41(6):1410–9. doi:10.1016/j.eurpolymj.2004.10.016.
Chen CC, Chueh JY, Tseng H, Huang HM, Lee SY. Preparation and characterization of biodegradable pla polymeric blends. Biomaterials. 2003;24(7):1167–73.
Cheng L, Lei L, Guo SR. In vitro and in vivo evaluation of praziquantel loaded implants based on peg/pcl blends. Int J Pharm. 2010;387(1–2):129–38. doi:10.1016/j.ijpharm.2009.12.010.
Cavalcanti LP, Konovalov O, Haas H. X-ray diffraction from paclitaxel-loaded zwitterionic and cationic model membranes. Chem Phys Lipids. 2007;150:58–65. doi:10.1016/j.chemphyslip.2007.06.219.
Cheng L, Guo S, Wu W. Characterization and in vitro release of praziquantel from poly([var epsilon]-caprolactone) implants. Int J Pharm. 2009;377(1–2):112–9. doi:10.1016/j.ijpharm.2009.05.007
Miyajima M, Koshika A, Okada J, Ikeda M, Nishimura K. Effect of polymer crystallinity on papaverine release from poly (l-lactic acid) matrix. J Control Release. 1997;49(2–3):207–15.
Park KI, Xanthos M. A study on the degradation of polylactic acid in the presence of phosphonium ionic liquids. Polym Degrad Stabil. 2009;94(5):834–44. doi:10.1016/j.polymdegradstab.2009.01.030.
Li C, Cheng L, Zhang Y, Guo S, Wu W. Effects of implant diameter, drug loading and end-capping on praziquantel release from pcl implants. Int J Pharm. 2010;386(1–2):23–9. doi:10.1016/j.ijpharm.2009.10.046.
Acknowledgments
This work was supported by National Natural Science Foundation of China (NSFC) (30872554, 81071244), Shanghai Science and Technology Committee (1052nm01000, 10441902000) and the Key program of Shanghai Municipal Education Committee (09ZZ24). The authors would like to thank Instrumental Analysis Center of Shanghai Jiao Tong University for their technical support.
Author information
Authors and Affiliations
Corresponding author
Additional information
X. Liu, L. Lei, and J.-W. Hou contributed equally to this work.
Rights and permissions
About this article
Cite this article
Liu, X., Lei, L., Hou, JW. et al. Evaluation of two polymeric blends (EVA/PLA and EVA/PEG) as coating film materials for paclitaxel-eluting stent application. J Mater Sci: Mater Med 22, 327–337 (2011). https://doi.org/10.1007/s10856-010-4213-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10856-010-4213-3