Advertisement

Electrospun Drug-Eluting Fibers for Biomedical Applications

  • Mădălina V. Natu
  • Hermínio C. de Sousa
  • Maria H. Gil
Chapter
Part of the Studies in Mechanobiology, Tissue Engineering and Biomaterials book series (SMTEB, volume 8)

Abstract

Electrospinning is a simple and versatile method to produce fibers using charged polymer solutions. As drug delivery systems, electrospun fibers are an excellent choice because of easy drug entrapment, high surface area, morphology control and biomimetic characteristics. Various drugs and biomolecules can be easily encapsulated inside or on fiber surface either during electrospinning or through post-processing of the fibers. Multicomponent fibers have attracted special attention because new properties and morphologies can be easily obtained through the combination of different polymers. The factors that affect the drug release such as construct geometry and thickness, diameter and porosity, composition, crystallinity, swelling capacity, drug loading, drug state, drug molecular weight, drug solubility in the release medium, drug–polymer–electrospinning solvent interactions are discussed. Mathematical models of drug release from electrospun fibers are reviewed and strategies to attain zero-order release and control of burst stage are considered. Finally, some results concerning release control in bicomponent fibers composed of poly(\(\varepsilon\)-caprolactone) and Lutrol F127 (poly(oxyethylene-b-oxypropylene-b-oxyethylene) are presented. The properties of the bicomponent fibers were studied in order to determine the effect of electrospinning processing on crystallinity, hydrophilicity and degradation. Acetazolamide and timolol maleate were loaded in the fibers in different concentrations in order to determine the effect of drug solubility in polymer, drug state, drug loading and fiber composition on morphology, drug distribution and release kinetics. Such electrospun drug eluting fibers can be used as basic elements of various implants and scaffolds for tissue regeneration.

Keywords

Drug Release Fiber Surface Water Contact Angle Drug Solubility Electrospun Fiber 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

FCT (Fundação para a Ciência e a Tecnologia) financial support is acknowledged by Mădălina V. Natu (SFRH/BD/30198/2006).

References

  1. 1.
    Fridrikh, S.V., Yu, J.H., Brenner, M.P., Rutledge, G.C.: Controlling the fiber diameter during electrospinning. Phys. Rev. Lett. doi: 10.1103/PhysRevLett.90.144502 (2003)
  2. 2.
    Huang, Z.-M., Zhang, Y.-Z., Kotaki, M., Ramakrishna, S.: A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Comp. Sci. Tech. (2003). doi: 10.1016/S0266-3538(03)00178-7
  3. 3.
    Hohman, M.M., Shin, M., Rutledge, G., Brenner, M.P.: Electrospinning and electrically forced jets. I. Stability theory. Phys. Fluids. (2001). doi: 10.1063/1.1383791
  4. 4.
    Rutledge, G.C., Fridrikh, S.V.: Formation of fibers by electrospinning. Adv. Drug Deliv. Rev. (2007). doi: 10.1016/j.addr.2007.04.020
  5. 5.
    McClure, M.J., Sell, S.A., Ayres, C.E., Simpson, D.G., Bowlin, G.L.: Electrospinning-aligned and random polydioxanone-polycaprolactone-silk fibroin-blended scaffolds: geometry for a vascular matrix. Biomed. Mater. (2009). doi: 10.1088/1748-6041/4/5/055010
  6. 6.
    Lopez-Rubio, A., Sanchez, E., Sanz, Y., Lagaron, J.M.: Encapsulation of living bifidobacteria in ultrathin PVOH electrospun fibers. Biomacromolecules (2009). doi: 10.1021/bm900660b
  7. 7.
    Heller, J.: Drug delivery systems. In: Ratner, B.D., Hoffman, A.S., Schoen, F.J., Lemons, J.E. (eds.) Biomaterials Science: An Introduction to Materials in Medicine, 1st edn. Academic Press, London (1996)Google Scholar
  8. 8.
    Cussler, E.L.: Diffusion Mass Transfer in Fluid Systems. Cambridge University Press, New York (1997)Google Scholar
  9. 9.
    Qi, H., Hu, P., Xu, J., Wang, A.: Encapsulation of drug reservoirs in fibers by emulsion electrospinning: morphology characterization and preliminary release assessment. Biomacromolecules (2006). doi: 10.1021/bm060264z
  10. 10.
    Liang, D., Luu, Y.K., Kim, K., Hsiao, B.S., Hadjiargyrou, M., Chu B.: In vitro non-viral gene delivery with nanofibrous scaffolds. Nucl Acids Res. (2005). doi: 10.1093/nar/gni171
  11. 11.
    Wang, Y., Wang, B., Qiao, W., Yin T.: A novel controlled release drug delivery system for multiple drugs based on electrospun nanofibers containing nanoparticles. J. Pharm. Sci. (2010). doi: 10.1002/jps.22189
  12. 12.
    Ayodeji, O., Graham, E., Kniss, D., Lannutti, J., Tomasko, D.: Carbon dioxide impregnation of electrospun polycaprolactone fibers. J Sup Fluids. (2007). doi: 10.1016/j.supu.2006.09.011
  13. 13.
    Chronakis, I.S., Milosevic, B., Frenot, A., Ye, L.: Generation of molecular recognition sites in electrospun polymer nanofibers via molecular imprinting. Macromolecules (2006). doi: 10.1021/ma052091w
  14. 14.
    Chronakis, I.S., Jakob, A., Hagstrom, B., Ye, L: Encapsulation and selective recognition of molecularly imprinted theophylline and 17\(\beta\)-estradiol nanoparticles within electrospun polymer nanofibers. Langmuir (2006). doi: 10.1021/la0613880
  15. 15.
    Ma, Z., Kotaki, M., Ramakrishna, S.: Surface modified nonwoven polysulphone (PSU) fiber mesh by electrospinning: a novel affinity membrane. J. Membr. Sci. (2006). doi: 10.1016/j.memsci.2005.07.038
  16. 16.
    Casper, C.L., Yang, W., Farach-Carson, M.C., Rabolt, J.F.: Coating electrospun collagen and gelatin fibers with Perlecan domain I for increased growth factor binding. Biomacromolecules (2007). doi: 10.1021/bm061003s
  17. 17.
    Casper, C.L., Yamaguchi, N., Kiick, K.L., Rabolt, J.F.: Functionalizing electrospun fibers with biologically relevant macromolecules. Biomacromolecules (2005). doi: 10.1021/bm050007e
  18. 18.
    Skotak, M., Leonov, A.P., Larsen, G., Noriega, S., Subramanian, A.: Biocompatible and biodegradable ultrafine fibrillar scaffold materials for tissue engineering by facile grafting of l-lactide onto chitosan. Biomacromolecules (2008). doi: 10.1021/bm800158c
  19. 19.
    Sawicka, K.M., Gouma, P.: Electrospun composite nanofibers for functional applications. J. Nanopart. Res. (2006). doi: 10.1007/s11051-005-9026-9
  20. 20.
    Liang, D., Hsiao, B.S., Chu, B.: Functional electrospun nanofibrous scaffolds for biomedical applications. Adv. Drug Deliv .Rev. (2007). doi: 10.1016/j.addr.2007.04.021
  21. 21.
    Lee, J.A., Krogman, K.C., Ma, M., Hill, R.M., Hammond, P.T., Rutledge, G.C.: Highly reactive multilayer-assembled TiO2 coating on electrospun polymer nanofibers. Adv. Mater. (2009). doi: 10.1002/adma.200802458
  22. 22.
    Lee, S.J., Yoo, J.J., Lim, G.J., Atala, A., Stitzel, J.: In vitro evaluation of electrospun nanofiber scaffolds for vascular graft application. J. Biomed. Mater. Res A. (2007). doi: 10.1002/jbm.a.31287
  23. 23.
    Zeng, J., Aigner, A., Czubayko, F., Kissel, T., Wendorff, J.H., Greiner, A: Poly(vinyl alcohol) nanofibers by electrospinning as a protein delivery system and the retardation of enzyme release by additional polymer coatings. Biomacromolecules (2005). doi: 10.1021/bm0492576
  24. 24.
    Bogntizki, M., Frese, T., Steinhart, M., Greiner, A., Wendorff, J.H.: Preparation of fibers With nanoscaled morphologies: electrospinning of polymer blends. Polym. Eng. Sci. (2001). doi: 10.1002/pen.10799
  25. 25.
    Wei, M., Kang, B., Sung, C., Mead, J.: Core–sheath structure in electrospun nanofibers from polymer blends. Macromol. Mater. Eng. (2006). doi: 10.1002/mame.200600284
  26. 26.
    Kalra, V., Kakad, P.A., Mendez, S., Ivannikov, T., Kamperman, M., Joo, Y.L.: Self-assembled structures in electrospun poly(styrene-block-isoprene) fibers. Macromolecules (2006). doi: 10.1021/ma052643a
  27. 27.
    Vaz, C.M., van Tuijl, S., Bouten, C.V.C., Baaijens, F.P.T.: Design of scaffolds for blood vessel tissue engineering using a multi-layering electrospinning technique. Acta Biomater. (2005). doi: 10.1016/j.actbio.2005.06.006
  28. 28.
    Pham, Q.P., Sharma, U., Mikos, A.G.: Electrospun poly(E-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds: characterization of scaffolds and measurement of cellular infiltration. Biomacromolecules (2006). doi: 10.1021/bm060680j
  29. 29.
    Hong, C.K., Yang, K.S., Oh, S.H., Ahn, J.-H., Cho, B.-H., Nah, C.: Effect of blend composition on the morphology development of electrospun fibres based on PAN/PMMA blends. Polym. Int. (2008). doi: 10.1002/pi.2481
  30. 30.
    You, Y., Youk, J.H., Lee, S.W., Min, B.-M., Lee, S.J., Park, W.H.: Preparation of porous ultrafine PGA fibers via selective dissolution of electrospun PGA/PLA blend fibers. Mater. Lett. (2006). doi: 10.1016/j.matlet.2005.10.007
  31. 31.
    Sisson, K., Zhang, C., Farach-Carson, M.C., Chase, D.B., Rabolt, J.F.: Evaluation of cross-linking methods for electrospun gelatin on cell growth and viability. Biomacromolecules (2009). doi: 10.1021/bm900036s
  32. 32.
    Lee, S.J., Oh, S.H., Liu, J., Soker, S., Atala, A., Yoo, J.J.: The use of thermal treatments to enhance the mechanical properties of electrospun poly(\(\varepsilon\)-caprolactone) scaffolds. Biomaterials (2008). doi: 10.1016/j.biomaterials.2007.11.024
  33. 33.
    Wang, X., Zhang, K., Zhu, M., Hsiao, B.S.., Chu, B.: Enhanced mechanical performance of self-bundled electrospun fiber yarns via post-treatments. Macromol. Rapid Commun. (2008). doi: 10.1002/marc.200700873
  34. 34.
    Tiwari, S.K., Tzezana, R., Zussman, E., Venkatraman, S.S.: Optimizing partition-controlled drug release from electrospun core–shell bers. Int. J. Pharm. (2010). doi: 10.1016/j.ijpharm.2010.03.021
  35. 35.
    Chew, S.Y., Wen, J., Yim, E.K.F., Leong, K.W.: Sustained release of proteins from electrospun biodegradable fibers. Biomacromolecules (2005).  doi: 10.1021/bm0501149
  36. 36.
    Zeng, J., Yang, L., Liang, Q., Zhang, X., Guan, H., Xu, X., Chen, X., Jin, X.: Influence of the drug compatibility with polymer solution on the release kinetics of electrospun fiber formulation. J. Con. Rel. (2005). doi: 10.1016/j.jconrel.2005.02.024
  37. 37.
    Xu, X., Yang, L., Xu, X., Wang, X., Chen, X., Liang, Q., Zeng, J., Jing, X.: Ultrafine medicated fibers electrospun from W/O emulsions. J. Con. Rel. (2005). doi: 10.1016/j.jconrel.2005.07.021
  38. 38.
    Kim, K., Luu, Y.K., Chang, C., Fang, D., Hsiao, B.S., Chu, B., Hadjiargyro, M.: Incorporation and controlled release of a hydrophilic antibiotic using poly(lactide-co-glycolide)-based electrospun nanofibrous scaffolds. J. Con. Rel. (2004). doi: 10.1016/j.jconrel.2004.04.009
  39. 39.
    Okuda, T., Tominaga, K., Kidoaki, S.: Time-programmed dual release formulation by multilayered drug-loaded nanober meshes. J. Con. Rel. (2009). doi: 10.1016/j.jconrel.2009.12.029
  40. 40.
    Ranganath, S.H., Wang, C.-H.: Biodegradable microfiber implants delivering paclitaxel for post-surgical chemotherapy against malignant glioma. Biomaterials (2008). doi: 10.1016/j.biomaterials.2008.04.002
  41. 41.
    Cui, W., Li, X., Zhu, X., Yu, G., Zhou, S., Weng, J.: Investigation of drug release and matrix degradation of electrospun poly(D,L-lactide) fibers with paracetanol inoculation. Biomacromolecules (2006). doi: 10.1021/bm060057z
  42. 42.
    Buschle-Diller, G., Cooper, J., Xie, Z., Wu, Y., Waldrup, J., Ren, X.: Release of antibiotics from electrospun bicomponent fibers. Cellulose (2007). doi: 10.1007/s10570-007-9183-3
  43. 43.
    Nie, H., Soh, B.W., Fu, Y.-.C, Wang, C.-H.: Three-dimensional fibrous PLGA/HAp composite scaffold for BMP-2 Delivery. Biotech. Bioeng. (2007). doi: 10.1002/bit.21517
  44. 44.
    Maretschek, S., Greiner, A., Kissel, T.: Electrospun biodegradable nanofiber nonwovens for controlled release of proteins. J. Con. Rel. (2008). doi: 10.1016/j.jconrel.2008.01.011
  45. 45.
    Kenawy, E.-R., Bowlin, G.L., Manseld, K., Layman, J., Simpson, D.G., Sanders, E.H., Wnek, G.E.: Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend. J. Con. Rel. (2002). doi: 10.1016/S0168-3659(02)00041-X
  46. 46.
    Xu, X., Chen, X., Xu, X., Lu, T., Wang, X., Yang, L., Jing, X.: BCNU-loaded PEG-PLLA ultrafine fibers and their in vitro antitumor activity against glioma C6 cells. J. Con. Rel. (2006). doi: 10.1016/j.jconrel.2006.05.031
  47. 47.
    Xie, Z., Buschle-Diller, G.: Electrospun Poly(D,L-lactide) fibers for drug delivery: the influence of cosolvent and the mechanism of drug release. J. Appl. Polym. Sci. (2009). doi: 10.1002/app.31026
  48. 48.
    Chien Y.W. (1992) Novel Drug Delivery Systems. Marcel Dekker, New YorkGoogle Scholar
  49. 49.
    Luong-Van, E., Grndahl, L., Chua, K.N., Leong, K.W., Nurcombe, V., Cool, S.M.: Controlled release of heparin from poly(\(\varepsilon\)-caprolactone) electrospun fibers. Biomaterials (2006). doi: 10.1016/j.biomaterials.2005.10.028
  50. 50.
    Zamani, M., Morshed, M., Varshosaz, J., Jannesari, M.: Controlled release of metronidazole benzoate from poly(\(\varepsilon\)-caprolactone) electrospun nanobers for periodontal diseases. Eur. J. Pharm. Biopharm. (2010). doi: 10.1016/j.ejpb.2010.02.002
  51. 51.
    Xie, J., Wang, C.-H.: Electrospun micro- and nanofibers for sustained delivery of paclitaxel to treat C6 glioma in vitro. Pharm. Res. (2006). doi: 10.1007/s11095-006-9036-z
  52. 52.
    Thakur, R.A., Florek, C.A., Kohn, J., Michniak, B.B.: Electrospun nanobrous polymeric scaffold with targeted drug release proles for potential application as wound dressing. Int. J. Pharm. (2008). doi: 10.1016/j.ijpharm.2008.07.033
  53. 53.
    Yu, D.-G., Shen, X.-X., Branford-White, C., White, K., Zhu, L.-M., Annie Blig S.W.: Oral fast-dissolving drug delivery membranes prepared from electrospun polyvinylpyrrolidone ultrafine fibers. Nanotechnology, (2009). doi: 10.1088/0957-4484/20/5/055104
  54. 54.
    Taepaiboon, P., Rungsardthong, U., Supaphol, P.: Drug-loaded electrospun mats of poly(vinyl alcohol) fibres and their release characteristics of four model drugs. Nanotechnology (2006). doi: 10.1088/0957-4484/17/9/041
  55. 55.
    Verreck, G., Chun, I., Rosenblatt, J., Peeters, J., Van Dijck, A., Mensch, J., Noppe, M., Brewste, M.E.: Incorporation of drugs in an amorphous state into electrospun nanofibers composed of a water-insoluble, nonbiodegradable polymer. J. Con. Rel. (2003). doi: 10.1016/S0168-3659(03)00342-0
  56. 56.
    Huang, Z.-M., He, C.-L., Yang, A., Zhang, Y., Han, X.-J., Yin, J., Q.W Encapsulating drugs in biodegradable ultrafine fibers through co-axial electrospinning. J. Biomed. Mater. Res. (2005). A. doi: 10.1002/jbm.a.30564
  57. 57.
    Natu, M.V., de Sousa, H.C., Gil, M.H.: Effects of drug solubility, state and loading on controlled release in bicomponent electrospun fibers. Int. J. Pharm. (2010). doi: 10.1016/j.ijpharm.2010.06.045
  58. 58.
    Sikareepaisan, P., Suksamrarn, A., Supaphol, P.: Electrospun gelatin fiber mats containing a herbal—Centella asiatica—extract and release characteristic of asiaticoside. Nanotechnology, (2008). doi: 10.1088/0957-4484/19/01/015102
  59. 59.
    Tzafriri, A.R.: Mathematical modeling of diffusion-mediated release from bulk degrading matrices. J. Con. Rel. (2000). doi: 10.1016/S0168-3659(99)00174-1
  60. 60.
    Kim, T.G., Lee, D.S., Park, T.G.: Controlled protein release from electrospun biodegradable fiber mesh composed of poly(\(\varepsilon\)-caprolactone) and poly(ethylene oxide). Int. J. Pharm. (2007). doi: 10.1016/j.ijpharm.2007.01.040
  61. 61.
    Perale, G., Arosio, P., Moscatelli, D., Barri, V., Mller, M., Maccagnan, S., Masi, M.: A new model of resorbable device degradation and drug release: transient 1-dimension diffusional model. J. Con. Rel. (2009). doi: 10.1016/j.jconrel.2009.02.014
  62. 62.
    Zong, X., Ran, Sh., Kim, K.-S., Fang, D., Hsiao, B.S., Chu B.: Structure and morphology changes during in vitro degradation of electrospun poly(glycolide-co-lactide) nanofiber membrane. Biomacromolecules (2003). doi: 10.1021/bm025717o
  63. 63.
    Peppas, N.A., Brannon-Peppas, L.: Water diffusion and sorption in amorphous macromolecular systems and foods. J. Food Eng. (1994). doi: 10.1016/0260-8774(94)90030-2
  64. 64.
    Zeng, J., Xu, X., Chen, X., Liang, Q., Bian, X., Yang, L., Jin, X.: Biodegradable electrospun fibers for drug delivery. J. Con. Rel. (2003). doi: 10.1016/S0168-3659(03)00372-9
  65. 65.
    Qi, M., Li, X., Yang, Y., Zhou, S.: Electrospun fibers of acid-labile biodegradable polymers containing ortho ester groups for controlled release of paracetamol. Eur. J. Pharm. Biopharm. (2008). doi: 10.1016/j.ejpb.2008.05.003
  66. 66.
    Taepaiboon, P., Rungsardthong, U., Supaphol, P.: Vitamin-loaded electrospun cellulose acetate nanober mats as transdermal and dermal therapeutic agents of vitamin A acid and vitamin E. Eur. J. Pharm. Biopharm. (2007). doi: 10.1016/j.ejpb.2007.03.018
  67. 67.
    Suwantong, O., Opanasopit, P., Ruktanonchai, U., Supaphol, P.: Electrospun cellulose acetate ber mats containing curcumin and release characteristic of the herbal substance. Polymer (2007). doi: 10.1016/j.polymer.2007.11.019
  68. 68.
    Verreck, G., Chun, I., Peeters, J., Rosenblatt, J., Brewste, M.E.: Preparation and characterization of nanofibers containing amorphous drug dispersions generated by electrostatic spinning. Pharm. Res. (2003) doi: 10.1023/A:1023450006281
  69. 69.
    Kenawy, E.-R., Abdel-Hay, F.I., El-Newehy, M.H., Wnek, G.E.: Processing of polymer nanobers through electrospinning as drug delivery systems. Mater. Chem. Phys. (2009). doi: 10.1016/j.matchemphys.2008.07.081
  70. 70.
    Jiang, H., Hu, Y., Li, Y., Zhao, P., Zhu, K., Che, W.: A facile technique to prepare biodegradable coaxial electrospun nanofibers for controlled release of bioactive agents. J. Con. Rel. (2005). doi: 10.1016/j.jconrel.2005.08.006
  71. 71.
    Tammaro, L., Russo, G., Vittoria, V.: Encapsulation of diclofenac molecules into Poly(\(\varepsilon\)-caprolactone) electrospun fibers for delivery protection. J. Nanomater. (2009). doi: 10.1155/2009/238206
  72. 72.
    Abidian, M.R., Kim, D.-H., Martin, D.C.: Conducting-polymer nanotubes for controlled drug release. Adv. Mater. (2006). doi: 10.1002/adma.200501726
  73. 73.
    Srikar, R., Yarin, A.L., Megaridis, C.M., Bazilevsky, A.V., Kelley, E.: Desorption-limited mechanism of release from polymer nanofibers. Langmuir. (2008). doi: 10.1021/la702449k
  74. 74.
    Panyam, J., Williams, D., Dash, A., Leslie-Pelecky, D., Labhasetwar, V.: Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticles. J. Pharm. Sci. (2004). doi: 10.1002/jps.20094
  75. 75.
    Drug card for timolol (DB00373), DrugBank database. http://www.drugbank.ca/drugs/DB00373. Cited 27 May 2010
  76. 76.
    Drug card for acetazolamide (DB00819), DrugBank database. http://www.drugbank.ca/drugs/DB00819. Cited 27 May 2010.
  77. 77.
    Marsac, P.J., Li, T., Taylor L.S.: Estimation of drug–polymer miscibility and solubility in amorphous solid dispersions using experimentally determined interaction parameters. Pharm. Res. (2009). doi: 10.1007/s11095-008-9721-1
  78. 78.
    Miyajima, M., Koshika, A., Okada, J., Ikeda, M., Nishimura, K.: Effect of polymer crystallinity on papaverine release from poly(L-lactic acid) matrix. J. Con. Rel. (1997). doi: 10.1016/S0168-3659(97)00081-3
  79. 79.
    Jeong, J.-C., Lee, J., Cho, K.: Effects of crystalline microstructure on drug release behavior of poly(\(\varepsilon\)-caprolactone) microspheres. J. Con. Rel. (2003). doi: 10.1016/S0168-3659(03)00367-5
  80. 80.
    Cui, W., Li, X., Zhou, S., Weng, J.: Degradation patterns and surface wettability of electrospun brous mats. Polym. Degrad. Stab. (2008). doi: 10.1016/j.polymdegradstab.2007.12.002
  81. 81.
    Kang, M., Jung, R., Kim, H.-S., Jin, H.-J.: Preparation of superhydrophobic polystyrene membranes by electrospinning. Colloids Surf. A Physicochem. Eng. Asp. (2008). doi: 10.1016/j.colsurfa.2007.04.122
  82. 82.
    Natu, M.V., Gil, M.H., de Sousa, H.C.: Supercritical solvent impregnation of poly(\(\varepsilon\)-caprolactone)/poly(oxyethylene-b-oxypropylene-b-oxyethylene) and poly(\(\varepsilon\)-caprolactone)/poly(ethylene-vinyl acetate) blends for controlled release applications. J. Sup. Fluids (2008). doi: 10.1016/j.supflu.2008.05.006
  83. 83.
    Hglund, A., Hakkarainen, M., Albertsson, A.-C.: Degradation profile of poly(\(\varepsilon\)-caprolactone)-the influence of macroscopic and macromolecular biomaterial Design. J. Macromol. Sci. A. doi: 10.1080/10601320701424487 (2007)

Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Mădălina V. Natu
    • 1
  • Hermínio C. de Sousa
    • 1
  • Maria H. Gil
    • 1
  1. 1.Department of Chemical EngineeringUniversity of CoimbraCoimbraPortugal

Personalised recommendations