Drug delivery devices

The Biomaterial Microsystems group is actively involved in the "The Danish National Research Foundation and Villum Foundation’s Center for Intelligent Drug delivery and sensing Using microcontainers and Nanomechanics - IDUN". In IDUN Drug, the research focus is on microcontainers for oral drug delivery. Our contribution is to develop new methods for the microfabrication of drug delivery devices.

Fabrication of SU-8 microcontainers

 
We have established the fabrication of microcontainers with the epoxy based negative photoresist SU-8. In IDUN these devices are used for initial testing of novel concepts for oral drug delivery. The containers are fabricated with two steps of photolithography on a fluorocarbon coated Si substrate. Typical dimensions are a container diameter of 300um and a container height of 300um with a reservoir volume of approximately 10 nL.

 
 
Fabrication of biodegradable microcontainers for oral drug delivery

 
For application in oral drug delivery it is required to replace SU-8 with biodegradable polymers. In the past years, we have introduced hot punching as a new method for the fabrication of microcontainers with polymers such as poly(L-lactic acid) (PLLA) or poly(caprolactone) (PCL). In future, we will investigate approaches such as roll-to-roll processing for high throughput fabrication of biodegradable drug delivery devices.

 

Left: Schematic process for fabrication of biodegradable microcontainers; Right: Array of PLLA microcontainers with height 100um


Drug loading in microcontainers

For initial testing microcontainers have been filled with drug powder. Additionally, inkjet printing has been used to fill the reservoirs with polymer followed by supercritical carbon dioxide (scCO2) impregnation with drugs such as ketoprofen. More recently, loading of microcontainers with drugs dissolved in polymer films has been demonstrated using hot punching. This method allows for simultaneous drug loading into large numbers of microncontainers.

 

Left: Process for loading of microcontainers by hot punching; Right: PLLA microcontainers filled with Furosemide/PCL drug/polymer matrix


Deposition of polymer lids on microcontainers

We have introduced spray coating as a flexible method deposition of degradable of dissolvable polymer lids on the microcontainers after filling them with drug powder. After sealing of the drug reservoirs with Eudragit L100 pH triggered drug release upon change from gastric to intestinal conditions has been demonstrated. A shadow mask was used to prevent polymer deposition in between the microcontainers and allow for selective coating of the drug delivery devices. 

Publications

  1. P. Marizza, L. Pontoni, T. Rindzevicius, J.F. Alopaeus, K. Su, J.A. Zeitler, S.S. Keller, I. Kikic, M. Moneghini, N. De Zordi, D. Solinas, A. Cortesi, A. Boisen, “Supercritical impregnation of polymer matrices spatially confined in microcontainers for oral drug delivery: Effect of temperature, pressure and time, J. Supercrit. Fluids 107 (2016) 145-152

  2. L.H. Nielsen, A. Melero, S.S. Keller, J. Jacobsen, T. Garrigues, T. Rades, A. Müllertz, A. Boisen, ”Polymeric microcontainers improve oral bioavailability of furosemide”, Int. J. Pharmaceutics 504 (2016) 98-109

  3. R.S. Petersen, S.S. Keller, A. Boisen, ”Hot punching of high-aspect-ratio 3D polymeric microstructures for drug delivery”, Lab Chip 5 (2015) 2576-2579

  4. L.H. Nielsen, J. Nagstrup, S. Gordon, S.S. Keller, J. Østergaard, T. Rades, A. Müllertz, A. Boisen, “pH-triggered drug release from biodegradable microwells for oral drug delivery”, Biomed. Microdevices 17 (2015) 55 

  5. R.S. Petersen, R. Mahshid, N.K. Andersen, S.S. Keller, H.N. Hansen, A. Boisen ”Hot embossing and mechanical punching of biodegradable microcontainers for oral drug delivery”, Microelec. Eng. 133 (2015) 104-109

  6. P. Marizza, S.S. Keller, A. Müllertz, A. Boisen ”Polymer-filled microcontainers for oral delivery loaded using supercritical impregnation”, J. Contr. Rel. 173 (2014) 1-9

  7. P. Marizza, S.S. Keller, A. Boisen ”Inkjet printing as a technique for filling of micro-wells with biocompatible polymers”, Microelec. Eng. 111 (2013) 391-395

  8. L.H. Nielsen, S.S. Keller, A. Boisen, A. Müllertz, T. Rades ”A slow cooling rate of indomethacin melt spatially confined in microcontainers increases the physical stability of the amorphous drug without influencing its biorelevant dissolution behaviour”, Drug Deliv. and Transl. Res. (2013) DOI 10.1007/s13346-013-0166-7

 Last updated 18.12.2016, Stephan Sylvest Keller
 
 
 
 
 
 
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https://www.nanolab.dtu.dk/FORSKNING/biomic/Microsystems/Drugdelivery-devices
16 DECEMBER 2019