Annals of Biomedical Engineering

, Volume 37, Issue 10, pp 2003–2017 | Cite as

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

  • Mark Chen
  • Houjin Huang
  • Erik Pierstorff
  • Eric Shin
  • Erik Robinson
  • Dean Ho
Article

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.

Keywords

Drug delivery Nanotechnology Nanomedicine Medical device Inflammation Cancer 

Notes

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.

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Copyright information

© Biomedical Engineering Society 2009

Authors and Affiliations

  • Mark Chen
    • 1
  • Houjin Huang
    • 2
  • Erik Pierstorff
    • 2
  • Eric Shin
    • 2
  • Erik Robinson
    • 3
  • Dean Ho
    • 2
    • 4
  1. 1.Departments of Biological Sciences and ChemistryNorthwestern UniversityEvanstonUSA
  2. 2.Departments of Biomedical and Mechanical EngineeringNorthwestern UniversityEvanstonUSA
  3. 3.Department of Chemical and Biological EngineeringNorthwestern UniversityEvanstonUSA
  4. 4.Robert H. Lurie Comprehensive Cancer Center, Northwestern UniversityChicagoUSA

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