Polymer Microneedles for Controlled-Release Drug Delivery
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As an alternative to hypodermic injection or implantation of controlled-release systems, this study designed and evaluated biodegradable polymer microneedles that encapsulate drug for controlled release in skin and are suitable for self-administration by patients.
Arrays of microneedles were fabricated out of poly-lactide-co-glycolide using a mold-based technique to encapsulate model drugs—calcein and bovine serum albumin (BSA)—either as a single encapsulation within the needle matrix or as a double encapsulation, by first encapsulating the drug within carboxymethylcellulose or poly-l-lactide microparticles and then encapsulating drug-loaded microparticles within needles.
By measuring failure force over a range of conditions, poly-lactide-co-glycolide microneedles were shown to exhibit sufficient mechanical strength to insert into human skin. Microneedles were also shown to encapsulate drug at mass fractions up to 10% and to release encapsulated compounds within human cadaver skin. In vitro release of calcein and BSA from three different encapsulation formulations was measured over time and was shown to be controlled by the encapsulation method to achieve release kinetics ranging from hours to months. Release was modeled using the Higuchi equation with good agreement (r 2 ≥ 0.90). After microneedle fabrication at elevated temperature, up to 90% of encapsulated BSA remained in its native state, as determined by measuring effects on primary, secondary, and tertiary protein structure.
Biodegradable polymer microneedles can encapsulate drug to provide controlled-release delivery in skin for hours to months.
Key Wordscontrolled-release drug delivery microneedles protein stability transdermal drug delivery
We thank Jin-Woo Park, Hak-Jun Sung, and Ping Ming Wang for helpful discussions and Gary Meek for photographing Fig. 3F. This work was supported in part by the National Institutes of Health. J.-H. P., M. G. A., and M. R. P. are members of the Microelectronics Research Center, and J.-H. P. and M. R. P. are members of the Institute for Bioengineering and Bioscience and the Center for Drug Design, Development and Delivery at Georgia Tech.
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