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Multi-pulse drug delivery from a resorbable polymeric microchip device

Abstract

Controlled-release drug delivery systems have many applications, including treatments for hormone deficiencies and chronic pain. A biodegradable device that could provide multi-dose drug delivery would be advantageous for long-term treatment of conditions requiring pulsatile drug release. In this work, biodegradable polymeric microchips were fabricated that released four pulses of radiolabelled dextran, human growth hormone or heparin in vitro. Heparin that was released over 142 days retained on average 96 ± 12% of its bioactivity. The microchips were 1.2 cm in diameter, 480–560 μm thick and had 36 reservoirs that could each be filled with a different chemical. The devices were fabricated from poly(L-lactic acid) and had poly(D,L-lactic-co-glycolic acid) membranes of different molecular masses covering the reservoirs. A drug delivery system can be designed with the potential to release pulses of different drugs at intervals after implantation in a patient by using different molecular masses or materials for the membrane.

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Figure 1: Diagram of polymeric microchip device.
Figure 2: Diagram of fabrication process for polymeric microchip device.
Figure 3: Cumulative percentage of initial loading released from microchip devices in vitro.
Figure 4: Cumulative percentage of initial loading released from microchip device in vitro.
Figure 5: Cumulative percentage of initial 3H-heparin loading released from microchip devices in vitro.

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Acknowledgements

This work was supported by the National Institutes of Health Bioengineering Research Partnership grant R24-AI47739-02. A.C.R.G. thanks the American Association of University Women and the National Science Foundation for fellowship funding. I.S.C. thanks the Korea Science and Engineering Foundation and the Brain Korea 21 project.

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Correspondence to Robert Langer.

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The technology reported in our manuscript (a polymeric microchip for molecular delivery) is licensed to MicroCHIPS, Inc., of Bedford, Massachusetts. Amy Grayson, Michael Cima and Robert Langer are shareholders in MicroCHIPS, Inc.

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Grayson, A., Choi, I., Tyler, B. et al. Multi-pulse drug delivery from a resorbable polymeric microchip device. Nature Mater 2, 767–772 (2003). https://doi.org/10.1038/nmat998

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