by Biomechanism
Bioengineers at Tufts University School of Engineering have developed a new silk-based microneedle system that delivers precise amounts of drugs over time and without refrigeration. The tiny needles can be fabricated under average temperature and pressure and from water, so they can be loaded with sensitive biochemical compounds and maintain their activity before use. They are also biodegradable and biocompatible.
The research paper “Fabrication of Silk Microneedles for Controlled-Release Drug Delivery” appeared in Advanced Functional Materials on December 2 online before print.
The Tufts researchers successfully demonstrated the ability of the silk microneedles to deliver a large-molecule, enzymatic model drug, horseradish peroxidase (HRP), at controlled rates while maintaining bioactivity. In addition, silk microneedles loaded with tetracycline were found to inhibit the growth of Staphylococcus aureus, demonstrating the potential of the microneedles to prevent local infections while also delivering therapeutics. Continue reading…
“By adjusting the silk protein's post-processing conditions and varying the silk protein's drying time, we were able to precisely control the drug release rates in laboratory experiments,” said Fiorenzo Omenetto, Ph.D., senior author on the paper. “The new system addresses long-standing drug delivery challenges, and we believe the technology could also be applied to other biological storage applications.”
The Drug Delivery Dilemma
While some drugs can be swallowed, others can’t survive the gastrointestinal tract. Hypodermic injections can be painful and don’t allow a slow release of medication. Only a limited number of small-molecule drugs can be transmitted through transdermal patches. Microneedles—no more than a micron in size and able to penetrate the upper layer of the skin without reaching nerves—are emerging as a painless new drug delivery mechanism. But their development has been limited by constraints ranging from harsh manufacturing requirements that destroy sensitive biochemicals to the inability to precisely control drug release or deliver sufficient drug volume to problems with infections due to the small skin punctures.
The process developed by the Tufts bioengineers addresses all of these limitations. The process involves ambient pressure and temperature and aqueous processing. Aluminium microneedle moulding masters were fabricated into needle arrays of about 500 µm needle height and tip radii of less than 10 µm. The elastomer polydimethylsiloxane (PDMS) was cast over the master to create a harmful mould; a drug-loaded silk protein solution was then cast over the mold. When the silk was dry, the drug-impregnated silk microneedles were removed. Further processing through water vapour annealing and various temperature, mechanical and electronic exposures provided control over the diffusivity of the silk microneedles and drug release kinetics.
“Changing the structure of the secondary silk protein enables us to ‘pre-program’ the properties of the microneedles with great precision,” said David L. Kaplan, Ph.D., coauthor of the study, chair of biomedical engineering at Tufts and a leading researcher on silk and other novel biomaterials. “This very flexible technology can be scaled up or down, shipped and stored without refrigeration and administered as easily as a patch or bandage. We believe the potential is enormous.”
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Other co-authors on the paper, all associated with the Department of Biomedical Engineering, are Konstantinos Tsioris, doctoral student; Waseem Raja, post-doctoral associate; Eleanor Pritchard, post-doctoral associate; and Bruce Panilaitis, research assistant professor.
Reference:
Tsioris, K., Raja, W. K., Pritchard, E. M., Panilaitis, B., Kaplan, D. L. and Omenetto, F. G. (2011), Fabrication of Silk Microneedles for Controlled-Release Drug Delivery. Advanced Functional Materials. doi: 10.1002/adfm.201102012
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