Skip to main content

Advertisement

SpringerLink
Log in

Parylene-Encapsulated Copolymeric Membranes as Localized and Sustained Drug Delivery Platforms

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Parylene is a biologically inert material capable of being deposited in conformal nanoscale layers on virtually any surface, making it a viable structural material for the fabrication of drug delivery devices, as well as implant coatings, sensors, and other biomedical technologies. Here we explore its novel drug delivery applications by using parylene to package the polymethyloxazoline-polydimethylsiloxane-polymethyloxazoline (PMOXA-PDMS-PMOXA) block copolymer membrane of a nanoscale thickness (~4 nm/layer) mixed with a therapeutic element, creating an active parylene-encapsulated copolymeric (APC) membrane for slow release drug delivery of dexamethasone (Dex), a potent anti-inflammatory and immunosuppressant synthetic glucocorticoid. Given current needs for localized therapeutic release for conditions such as cancer, post-surgical inflammation, wound healing, regenerative medicine, to name a few, this stand-alone and minimally invasive implantable technology may impact a broad range of medical scenarios. To evaluate the applicability of the APC membrane as a biocompatible drug delivery system, real-time polymerase chain reaction (RT-PCR) was performed to investigate the expression of cytokines that regulate cellular stress and inflammation as a result of in vitro RAW264.7 macrophage cell growth on the APC membrane. Significant decreases in relative mRNA levels of IL-6, TNF-α, and iNOS were observed. Dex functionalized APC membranes were further found to effectively slow-elute the drug via confocal microscopy, with a confirmed extended elution capability over a period of several days, undergoing phosphate buffered saline washes between time points. In addition, we examined the membrane surface through atomic force microscopy (AFM) to examine Dex/copolymer deposition, and to characterize the surface of the APC membrane. Furthermore, we evaluated the effects of incubation with the APC membrane in solution on macrophage growth behavior and cellular adhesion, including the physical properties of parylene and the copolymer to elucidate the anti-adhesive responses we observed. The results of this study will provide insight into ultra-thin and flexible devices of parylene-encapsulated copolymer membranes as platform drug delivery technologies capable of localized and precision therapeutic drug elution.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. 55. Akakura, K., H. Suzuki. T. Ueda, A. Komiya, T. Ichikawa, T. Igarashi, H. Ito. 2003. Possible mechanism of dexamethasone therapy for prostate cancer: suppression of circulating level of interleukin-6. The Prostate. 56: 106-109. doi:10.1002/pros.10231

    Article  CAS  PubMed  Google Scholar 

  2. 25. Boduroglu, S., M. Cetinkaya, W.J. Dressick, A. Singh, and M.C. Demirel. 2007. Controlling the wettability and adhesion of nanostructured poly-(p-xylylene) films. Langmuir. 23: 11391-11395. doi:10.1021/la7025413

    Article  CAS  PubMed  Google Scholar 

  3. 48. Brodbeck, W.G., J. Patel, G. Voskerician, E. Christenson, M.S. Shive, Y. Nakayama, T. Matsuda, N.P. Ziats, J.M. Anderson. 2002. Biomaterial adherent macrophage apoptosis is increased by hydrophilic and anionic substrates in vivo. Proc. Nat. Acad. Sci-USA. 99: 10287-10292. doi:10.1073/pnas.162124199

    Article  CAS  PubMed  Google Scholar 

  4. 3. Burt, H.M., W.L. Hunter. 2006. Drug-eluting stents: A multidisciplinary success story. Adv. Drug Del. Rev. 58: 350-357. doi:10.1016/j.addr.2006.01.014

    Article  CAS  PubMed  Google Scholar 

  5. 4. Burt, H.M., and W.L. Hunter. 2006. Drug-eluting stents: an innovative multidisciplinary delivery platform. Adv. Drug Del. Rev. 58: 345-346. doi:10.1016/j.addr.2006.02.001

    Article  CAS  PubMed  Google Scholar 

  6. 45. Buzin, A.I., D.S. Bartolome, K.A. Mailyan, A.V. Pebalk, S.N. Chvalun. 2006. Surface morphology of poly(cyano-p-xylylene) thin films. Polym. Sci. Ser. A. 48: 961-966. doi:10.1134/S0965545X06090112

    Article  Google Scholar 

  7. 35. Chen, P., D.C. Rodger, E.M. Meng, M.S. Humayun, Y.-C. Tai. 2007. Surface-micromachined parylene dual valves for on-chip unpowered microflow regulation. J. Microelectromech. Sys. 16: 223-231. doi:10.1109/JMEMS.2006.889534

    Article  CAS  Google Scholar 

  8. 1. Cheng, J., B.A. Teply, S.Y. Jeong, C.H. Yim, D. Ho, I. Sherifi, S. Jon, O.C. Farokhzad, A. Khademhosseini, R.S. Langer. 2006. Magnetically responsive polymeric microparticles for oral delivery of protein drugs. Pharmaceutical Res. 23: 557-564. doi:10.1007/s11095-005-9444-5

    Article  CAS  PubMed  Google Scholar 

  9. 22. Chow, E., E. Pierstorff, G. Cheng, D. Ho. 2008. Nanofilm copolymer platform for controlled drug delivery. ACS Nano. 2: 33-40. doi:10.1021/nn7000917

    Article  CAS  PubMed  Google Scholar 

  10. 43. Chow, E.K., E. Pierstorff, G. Cheng, Y.-C. Tai, D. Ho. 2007. Attenuation of Cellular Inflammation Using Glucocorticoid-Functionalized Copolymers. IEEE Proc. NEMS. 2:1039-1043.

    Google Scholar 

  11. 9. Chung, H.J., T.G. Park. 2007. Surface engineered and drug releasing pre-fabricated scaffolds for tissue engineering. Adv. Drug Del. Rev. 59: 249-262. doi:10.1016/j.addr.2007.03.015

    Article  CAS  PubMed  Google Scholar 

  12. 53. Cohen J.J., R.P. Schlerimer, H.N. Claman, A.L. Oronsky. 1989. Anti-Inflammatory Steroid Action, Basic and Clinical Aspects. San Diego: Academic Press. pp. 111-131.

    Google Scholar 

  13. 46. Collier, T.O., J.M. Anderson, W.G. Brodbeck, T. Barber, K.E. Healy. 2004. Inhibition of macrophage development and foreign body giant cell formation by hydrophilic interpenetrating polymer network. J. Biomed. Mater. Res. Part A. 69A: 644-650. doi:10.1002/jbm.a.30030

    Article  PubMed  Google Scholar 

  14. 52. D’Acquisto, F., L. Cicatiello, T. Iuvone, A. Ialenti, A. Ianaro, H. Esumi, A. Weisz, R. Carnuccio. 1997. Inhibition of inducible nitric oxide synthase gene expression by glucocorticoid-induced protein(s) in lipopolysaccharide-stimulated J774 cells. Euro. J. Pharmacol. 339: 87-95. doi:10.1016/S0014-2999(97)01361-7

    Article  PubMed  Google Scholar 

  15. 59. De Vera, M.E., B.S. Taylor, Q. Wang, R.A. Shapiro, T.R. Billiar, D.A. Geller. 1997. Dexamethasone suppresses iNOS gene expression by upregulating I-κBα and inhibiting NF-κB. Am. J. Physiol. Gastrointest. Liver Physiol. 273: 1290-1296.

    Google Scholar 

  16. 29. Fan, Z., J.M. Engel, J. Chen, C. Liu. 2004. Parylene surface-micromachined membranes for sensor applications. J. Microelectromechanical Sys. 13: 484-490. doi:10.1109/JMEMS.2004.825295

    Article  Google Scholar 

  17. 33. Fontaine, A.B., K. Koelling, S.D. Passos, J. Cearlock, R. Hoffman, D.G. Spigos. 1996. Polymeric surface modifications of tantalum stents. J. Endovasc. Surg. 3: 276-283. doi:10.1583/1074-6218(1996)003<0276:PSMOTS>2.0.CO;2

    Article  CAS  PubMed  Google Scholar 

  18. 63. Gasion, J.P.B., J.F.J. Cruz. 2006. Improving efficacy of intravesical chemotherapy. Euro. Urol. 50: 225-234. doi:10.1016/j.eururo.2006.05.035

    Article  CAS  PubMed  Google Scholar 

  19. 21. Gifford, R., M.M. Batchelor, Y. Lee, G. Gokulrangan, M.E. Meyerhoff, G.S. Wilson. 2005. Mediation ofin vivo glucose sensor inflammatory response via nitric oxide release. J. Biomed. Mater. Res. A.75: 755-766. doi:10.1002/jbm.a.30359

    PubMed  Google Scholar 

  20. 47. Goschel, U., H. Walter. 2000. Surface film formation by chemical vapor deposition of di-p-xylylene: ellipsometrical, atomic force microscopy, and x-ray studies. Langmuir. 16: 2887-2892. doi:10.1021/la9908743

    Article  Google Scholar 

  21. 38. Grattan, D.W., M. Bilz. 1991. The Thermal Aging of Parylene and the Effect of Antioxidant. Studies in Conservation. 36: 44-52. doi:10.2307/1506451

    Article  CAS  Google Scholar 

  22. 39. Greiner, A. 1996. Poly(p-xylylene)s (structure, properties, and applications). The Polymeric Materials Encyclopedia. 9: 7171-7180.

    Google Scholar 

  23. 10. Grube, E., L. Buellesfeld, F.J. Neumann, S. Verheye, A. Abizaid, D. McClean, R. Mueller, A. Lansky, R. Mehran, R. Costa, U. Gerckens, B. Trauthen, P.J. Fitzgerald. 2007. Six-month clinical and angiographic results of a dedicated drug-eluting stent for the treatment of coronary bifurcation narrowings. Am. J. Cardiol. 99: 1691-1697. doi:10.1016/j.amjcard.2007.01.043

    Article  CAS  PubMed  Google Scholar 

  24. 31. He, Q., E. Meng, Y.-C. Tai, C.M. Rutherglen, J. Erickson, J. Pine. 2003. Parylene neuro-cages for live neural networks study. Proc. Transducers. 12: 995-998.

    Google Scholar 

  25. 51. Hoffmann, A., D. Baltimore. 2006. Circuitry of nuclear factor κB signaling. Immunol. Rev. 210: 171-186. doi:10.1111/j.0105-2896.2006.00375.x

    Article  PubMed  Google Scholar 

  26. 20. Konttinen, Y.T., D. Zhao, A. Beklen, G. Ma, M. Takagi, M. Kivela-Rajamaki, N. Ashammakhi, S. Santavirta. 2005. The microenvironment around total hip replacement prostheses. Clin. Orthop. Relat. Res. 430: 28-38. doi:10.1097/01.blo.0000150451.50452.da

    Article  PubMed  Google Scholar 

  27. 58. Korhonen, R., A. Lahti, M. Hamalainen, H. Kankaanranta, E. Moilanen. 2002. Dexamethasone inhibits inducible nitric-oxide synthase expression and nitric oxide production by destabilizing mRNA in lipopolysaccharide-treated macrophages. Mol. Pharmacol. 62: 698-704. doi:10.1124/mol.62.3.698

    Article  CAS  PubMed  Google Scholar 

  28. 5. Krucoff, M.W., A. Boam, D.G. Schultz. 2007. Drug-eluting stents “deliver heartburn”: How do we spell relief going forward? Circulation. 115: 2990-2994. doi:10.1161/CIRCULATIONAHA.107.707778

    Article  PubMed  Google Scholar 

  29. 26. Krupin, T., A.I. Mandell, S.M. Podos, B. Becker. 1976. Topical corticosteroid therapy and pituitary-adrenal function. Arch. Ophthalmol. 94: 919-920.

    CAS  PubMed  Google Scholar 

  30. 28. Lam, R., M. Chen, E. Pierstorff, H. Huang, E. Osawa, D. Ho. 2008. Nanodiamond-Embedded Microfilm Devices for Localized Chemotherapeutic Elution. ACS Nano. 2: 2095-2102. doi:10.1021/nn800465x

    Article  CAS  PubMed  Google Scholar 

  31. 49. Leporatti, S., A. Gerth, G. Kohler, B. Kohlstrunk, S. Hauschildt, E. Donath. 2006. Elasticity and adhesion of resting and lipopolysaccharide-stimulated macrophages. FEBS Lett. 580: 450-454. doi:10.1016/j.febslet.2005.12.037

    Article  CAS  PubMed  Google Scholar 

  32. 56. Maeda, K., K. Yoshida, I. Ichimiya, M. Suzuki. 2005. Dexamethasone inhibits tumor necrosis factor-α-induced cytokine secretion from spiral ligament fibrocytes. Hearing Res. 202: 154-160. doi:10.1016/j.heares.2004.08.022

    Article  CAS  PubMed  Google Scholar 

  33. 6. Malafaya, P.B., G.A. Silva, E.T. Baran, R.L. Reis. 2002. Drug delivery therapies I General trends and its importance on bone tissue engineering applications. Curr. Opin. Sol. State and Mat. Sci. 6:283-295. doi:10.1016/S1359-0286(02)00075-X

    Article  CAS  Google Scholar 

  34. 50. Nakashima, Y., D.-H. Sun, M.C.D. Trindade, W.J. Maloney, S.B. Goodman, D.J. Schurman, R.L. Smith. 1999. Signaling pathways for tumor necrosis factor-α and interleukin-6 expression in human macrophages exposed to titanium-alloy particulate debris in vitro J. Bone Joint Surg. Am. 81: 603-615. doi:10.1302/0301-620X.81B1.8884

    Article  CAS  PubMed  Google Scholar 

  35. 42. Nardin, C., M. Winterhalter, W. Meier. 2000. Giant free-standing ABA triblock copolymer membranes. Langmuir. 16: 7708-7712. doi:10.1021/la000204t

    Article  CAS  Google Scholar 

  36. 37. Neeves, K.B., C.T. Lo, C.P. Foley, W.M. Saltzman, W.L. Olbricht. 2006. Fabrication and characterization of microfluidic probes for convection enhanced drug delivery. J. Control. Rel. 111: 252-262. doi:10.1016/j.jconrel.2005.11.018

    Article  CAS  PubMed  Google Scholar 

  37. 60. Pascual, G., C.K. Glass. 2006. Nuclear receptors versus inflammation: mechanisms of transrepression. Trends Endocrinol. Metab. 17: 321-327. doi:10.1016/j.tem.2006.08.005

    Article  CAS  PubMed  Google Scholar 

  38. 12. Pfisterer, M., H.P. Brunner-La Rocca, P.T. Buser, P. Rickenbacher, P. Hunziker, C. Mueller, R. Jeger, F. Bader, S. Osswald, C. Kaiser. 2006. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents. An observational study of drug-eluting versus bare-metal stents. J. Am. Coll. Cardiol. 48: 2584-2591. doi:10.1016/j.jacc.2006.10.026

    Article  CAS  PubMed  Google Scholar 

  39. 41. Pierstorff, E., M. Krucoff, D. Ho. 2008. Apoptosis induction and attenuation of inflammatory gene expression in murine macrophages via multitherapeutic nanomembranes. Nanotechnology. 19: 265103-265112. doi:10.1088/0957-4484/19/26/265103

    Article  Google Scholar 

  40. 40. Schäfer, O., F. Brink-Spalink, C. Schmidt, J.H. Wendorff, C. Witt, T. Kissel, A. Greiner. 1999. Synthesis and properties of omega-phenylalkyl-substituted poly(p-xylylene)s prepared by base-induced 1,6-dehydrohalogenation. Macromol. Chem. Phys. 200: 1942-1949. doi:10.1002/(SICI)1521-3935(19990801)200:8<1942::AID-MACP1942>3.0.CO;2-H

    Article  Google Scholar 

  41. 30. Shin, Y.S., K. Cho, S.H. Lim, S. Chung, S. Park, C. Chung, D. Han, J.K. Chang. 2003. PDMS-based micro PCR chip with Parylene coating. J. Micromech. Microeng. 13: 768-774. doi:10.1088/0960-1317/13/5/332

    Article  CAS  Google Scholar 

  42. 18. Sigler, M., T. Paul, R.G. Grabitz. 2005. Biocompatibility screening in cardiovascular implants. Z. Kardiol. 94: 383-391. doi:10.1007/s00392-005-0231-4

    Article  CAS  PubMed  Google Scholar 

  43. 62. Smyth, G.P., P.P. Stapleton, T.A. Freeman, E.M. Concannon, J.R. Mestre, M. Duff, S. Maddali, J.M. Daly. 2004. Glucocorticoid pretreatment induces cytokine overexpression and nuclear factor-κB activation in macrophages. J. Surg. Res. 116: 253-261. doi:10.1016/S0022-4804(03)00300-7

    Article  CAS  PubMed  Google Scholar 

  44. 57. Soderberg, M., F.Raffalli-Mathieu, M.A. Lang. 2007. Regulation of the murine inducible nitric oxide synthase gene by dexamethasone involves a heterogeneous nuclear ribonucleoprotein I (hnRNPI) dependent pathway. Mol. Immunology. 44: 3204-3210. doi:10.1016/j.molimm.2007.01.029

    Article  PubMed  Google Scholar 

  45. 2. Sokolsky-Papkov, M., K. Agashi, A. Olaye, K. Shakesheff, A.J. Domb. 2007. Polymer carriers for drug delivery in tissue engineering. Adv. Drug Del. Rev. 59: 187-206. doi:10.1016/j.addr.2007.04.001

    Article  CAS  PubMed  Google Scholar 

  46. 61. Sorrells, S.F., R.M. Sapolsky. 2007. An inflammatory review of glucocorticoids in the CNS. Brain, Behavior, and Immunity. 21: 259-272. doi:10.1016/j.bbi.2006.11.006

    Article  CAS  PubMed  Google Scholar 

  47. 23. Stark, N. 1996. Literature review: biological safety of parylene c. Medical Plastics and Biomaterials. 3: 30-35.

    Google Scholar 

  48. 19. Sutherland, K., J.R. Mahoney, A.J. Coury, and J.W. Eaton. 1993. Degradation of biomaterials by phagocyte-derived oxidants. J. Clin. Invest. 92: 2360-2367. doi:10.1172/JCI116841

    Article  CAS  PubMed  Google Scholar 

  49. 36. Takeuchi, S., D. Ziegler, Y. Toshida, K. Mabuchi, T. Suzuki. 2005. Parylene flexible neural probes integrated with microfluidic channels. Lab on a Chip. 5: 519-523. doi:10.1039/b417497f

    Article  CAS  PubMed  Google Scholar 

  50. 16. Tao, S. L., Desai, T. A. 2005. Gastrointestinal patch systems for oral drug delivery. Drug Discovery Today. 909-915. doi:10.1016/S1359-6446(05)03489-6

    Article  CAS  PubMed  Google Scholar 

  51. 17. Tao, S. L., Desai, T. A. 2005. Microfabrication of multilayer, asymmetric, polymeric devices for drug delivery. Advanced Materials. 17: 1625-1630. doi:10.1002/adma.200500017

    Article  CAS  Google Scholar 

  52. 32. Tooker, A., E. Meng, J. Erickson, Y.-C. Tai, J. Pine. 2005. Biocompatible Parylene Neurocages. IEEE Eng. in Med. And Bio. 24: 30-33.

    Article  PubMed  Google Scholar 

  53. 54. Truss, M., M. Beato. 1993. Steroid hormone receptors: interaction with deoxyribonucleic acid and transcription factors. Endocr. Rev. 51: 459-479.

    Google Scholar 

  54. 15. Tsutsui, Y., K. Tomizawa, M. Nagita, H. Michiue, T. Nishiki, I. Ohmori, M. Seno, H. Matsui. 2007. Development of bionanocapsules targeting brain tumors. J. Control. Rel. 122: 159-164. doi:10.1016/j.jconrel.2007.06.019

    Article  CAS  PubMed  Google Scholar 

  55. 11. Westedt, U., M. Wittmar, M. Hellwig, P. Hanefeld, A. Greiner, A.K. Schaper, T. Kissel. 2006. Paclitaxel releasing films consisting of poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) and their potential as biodegradable stent coatings. J. Control. Rel. 111: 235-245. doi:10.1016/j.jconrel.2005.12.012

    Article  CAS  PubMed  Google Scholar 

  56. 24. Wolgemuth, L. 2000. Assessing the performance and suitability of parylene coating. Med. Dev. Diag. Ind. 22: 42-49.

    Google Scholar 

  57. 7. Wong, H.L., R. Bendayan, A.M. Rauth, Y. Li, X.Y. Wu. 2007. Chemotherapy with anticancer drugs encapsulated in solid lipid nanoparticles. Adv. Drug Del. Rev. 59: 491-504. doi:10.1016/j.addr.2007.04.008

    Article  CAS  PubMed  Google Scholar 

  58. 13. Yang, C., H.M. Burt. 2006. Drug-eluting stents: Factors governing local pharmacokinetics Adv. Drug Del. Rev. 58:402-411. doi:10.1016/j.addr.2006.01.017

    Article  CAS  PubMed  Google Scholar 

  59. 44. Yang, G.-R., S. Ganguli, J. Karcz, W.N. Gill, T.-M. Lu. 1998. High deposition rate parylene films. J. Crystal Growth. 183: 385-390. doi:10.1016/S0022-0248(97)00428-4

    Article  CAS  Google Scholar 

  60. 27. Zeng, J., A. Aigner, F. Czubayko, T. Kissel, J. H. Wendorff, A. Greiner. 2005. Poly(vinyl alcohol) nanofibers by electrospinning as a protein delivery system and the retardation of enzyme release by additional polymer coatings. Biomacromol. 6: 1484-1488. doi:10.1021/bm0492576

    Article  CAS  PubMed  Google Scholar 

  61. 8. Zhang, G., L.J. Suggs. 2007. Matrices and scaffolds for drug delivery in vascular tissue engineering. Adv. Drug Del. Rev. 59: 360-373. doi:10.1016/j.addr.2007.03.018

    Article  CAS  PubMed  Google Scholar 

  62. 14. Zhong, Y., R.V. Bellamkonda. 2007. Dexamethasone coated neural probes elicit attenuated inflammatory response and neuronal loss compared to uncoated neural probes. Brain Res. 1148: 15-27. doi:10.1016/j.brainres.2007.02.024

    Article  CAS  PubMed  Google Scholar 

  63. 34. Ziegler, D., T. Suzuki, S. Takeuchi. 2006. Fabrication of flexible neural probes with built-in microfluidic channels by thermal bonding of parylene. J. Microelectromech. Sys. 15: 1477-1482. doi:10.1109/JMEMS.2006.879681

    Article  CAS  Google Scholar 

Download references

Acknowledgments

D. H. gratefully acknowledges support from a National Science Foundation CAREER Award, V Foundation for Cancer Research V Scholars Award, National Science Foundation Center for Scalable and Integrated NanoManufacturing (SINAM) Grant DMI-0327077, Wallace H. Coulter Foundation Early Career Award in Translational Research, and National Institutes of Health grant U54 A1065359. M. Chen acknowledges support from the Weinberg College of Arts and Sciences of Northwestern University.

Author information

Authors and Affiliations

  1. Departments of Biological Sciences and Chemistry, Northwestern University, Evanston, IL, 60208, USA

    Mark Chen

  2. Departments of Biomedical and Mechanical Engineering, Northwestern University, 2145 Sheridan Road, Room E310, Evanston, IL, 60208, USA

    Houjin Huang, Erik Pierstorff, Eric Shin & Dean Ho

  3. Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, 60208, USA

    Erik Robinson

  4. Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, 60611, USA

    Dean Ho

Authors
  1. Mark Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Houjin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Erik Pierstorff
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eric Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Erik Robinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dean Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dean Ho.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, M., Huang, H., Pierstorff, E. et al. Parylene-Encapsulated Copolymeric Membranes as Localized and Sustained Drug Delivery Platforms. Ann Biomed Eng 37, 2003–2017 (2009). https://doi.org/10.1007/s10439-009-9662-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-009-9662-9

Keywords

Search

Navigation