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Nanochannel Technology for Constant Delivery of Chemotherapeutics: Beyond Metronomic Administration

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ABSTRACT

Purpose

The purpose of this study is to demonstrate the long-term, controlled, zero-order release of low- and high-molecular weight chemotherapeutics through nanochannel membranes by exploiting the molecule-to-surface interactions presented by nanoconfinement.

Methods

Silicon membranes were produced with nanochannels of 5, 13 and 20 nm using standardized industrial microfabrication techniques. The study of the diffusion kinetics of interferonα-2b and leuprolide was performed by employing UV diffusion chambers. The released amount in the sink reservoir was monitored by UV absorbance.

Results

Continuous zero-order release was demonstrated for interferonα-2b and leuprolide at release rates of 20 and 100 μg/day, respectively. The release rates exhibited by these membranes were verified to be in ranges suitable for human therapeutic applications.

Conclusions

Our membranes potentially represent a viable nanotechnological approach for the controlled administration of chemotherapeutics intended to improve the therapeutic efficacy of treatment and reduce many of the side effects associated with conventional drug administration.

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ACKNOWLEDGEMENTS

The authors are grateful to Erika Zabre for her support in the experimental analysis and in the editing of the manuscript. This project has been supported with federal funds from NASA (NNJ06HE06A and NNX08AW91G), Department of Defense (DODW81XWH-09-1-0212), as well as funds from State of Texas Emerging Technology Fund, NanoMedical Systems (NMS), and Alliance of NanoHealth (ANH). The authors acknowledge the Texas Advanced Computing Center (TACC) at the University of Texas at Austin for providing HPC resources that have contributed to the research results reported within this paper.

DISCLOSURE

Grattoni A, Fine D, Liu X and Ferrari M hereby disclose a personal financial interest in NanoMedical Systems, Inc.

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Authors and Affiliations

  1. Department of NanoMedicine and Biomedical Engineering (nBME), The University of Texas Medical School at Houston, Houston, Texas, USA

    Alessandro Grattoni, Haifa Shen, Daniel Fine, Arturas Ziemys, Jaskaran S. Gill, Xuewu Liu & Mauro Ferrari

  2. NanoMedical Systems, Inc., Austin, Texas, USA

    Lee Hudson, Sharath Hosali & Randy Goodall

  3. Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Mauro Ferrari

  4. Department of Bioengineering, Rice University, Houston, Texas, USA

    Mauro Ferrari

  5. 1825 Pressler St. Suite 537, Houston, Texas, 77030, USA

    Mauro Ferrari

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  1. Alessandro Grattoni
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  9. Xuewu Liu
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Correspondence to Mauro Ferrari.

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Grattoni, A., Shen, H., Fine, D. et al. Nanochannel Technology for Constant Delivery of Chemotherapeutics: Beyond Metronomic Administration. Pharm Res 28, 292–300 (2011). https://doi.org/10.1007/s11095-010-0195-6

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  • DOI: https://doi.org/10.1007/s11095-010-0195-6

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