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Nanodiamond-Embedded Microfilm Devices for Localized Chemotherapeutic Elution

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Robert Lam†, Mark Chen†, Erik Pierstorff†, Houjin Huang†, Eiji Osawa‡ and Dean Ho†§*

^† Departments of Biomedical and Mechanical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois 60208

^‡ Nanocarbon Research Institute, Ltd., Asama Research Extension Center, Shinshu University, 3-15-1 Tokita, Ueda, Nagano 386-8567, Japan

^§ Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois 60611

ACS Nano, 2008, 2 (10), pp 2095–2102

DOI: 10.1021/nn800465x

Publication Date (Web): October 2, 2008

* Address correspondence to d-ho@northwestern.edu.

Section:

Pharmaceuticals

Abstract

Nanodiamonds (NDs) of 2−8 nm diameters physically bound with the chemotherapeutic agent doxorubicin hydrochloride (DOX) were embedded within a parylene C polymer microfilm through a facile and scalable process. The microfilm architecture consists of DOX-ND conjugates sandwiched between a base and thin variable layer of parylene C which allows for modulation of release. Successive layers of parylene and the DOX-ND conjugates were characterized through atomic force microscopy (AFM) images and drug release assays. Elution rates were tested separately over a period of 8 days and up to one month in order to illustrate the release characteristics of the microfilms. The microfilms displayed the stable and continuous slow-release of drug for at least one month due to the powerful sequestration abilities of the DOX-ND complex and the release-modulating nature of the thin parylene layer. Since the fabrication process is devoid of any destructive steps, the DOX-ND conjugates are unaffected and unaltered. A DNA fragmentation assay was performed to illustrate this retained activity of DOX under biological conditions. Specifically, in this work we have conferred the ability to tangibly manipulate the NDs in a polymer-packaged microfilm format for directed placement over diseased areas. By harnessing the innate ND benefits in a biostable patch platform, extended targeted and controlled release, possibly relevant toward conditions such as cancer, viral infection, and inflammation, where complementary alternatives to systemic drug release enabled by the microfilm devices, can allow for enhanced treatment efficacy.

Keywords:

nanodiamonds; nanomedicine; nanomaterials; slow-release; drug delivery

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