Thermally Driven Release of Oxycodone from Poly(ester urea) Thin Films by Printed Microheaters for Transdermal Delivery

Opioids are widely considered to be one of the most effective pain management strategies, but current prescription and distribution models have resulted in high rates of misuse, addiction, and overdose. An alternative to the systemic delivery of opioids is drug-loaded patches for transdermal delivery, currently clinically used with lidocaine and fentanyl. However, significant active pharmaceutical ingredients (API) often remain in the patches at the end of their useful lifetime. Herein, we report the use of oxycodone-loaded, biodegradable amino acid-based poly(ester urea) (PEU) films with thermally driven release behavior. Oxycodone load was varied to achieve a near-physiological glass transition temperature (<i>T</i>_g), and greater oxycodone release was achieved at temperatures approaching and above the material's <i>T</i>_g. Pharmacokinetic data from an <i>in vivo</i> mouse model incorporating a transdermal application of oxycodone-loaded PEU patches demonstrated no detectable passive release of oxycodone in the plasma. Tissue analysis of the skin surrounding the patch determined there were over 4-fold greater oxycodone levels in the skin than those found following a subcutaneous injection of oxycodone after 24 h. To achieve higher oxycodone release by targeting the thermally driven release behavior in a transdermal setup, microheaters were fabricated by aerosol jet printing of silver nanowires. Oxycodone release doubled in a Franz cell experiment with the use of microheaters, demonstrating significant thermally driven release. This work showcases the temperature-accelerated drug release behavior of oxycodone from PEU films and the future potential for transdermal drug delivery using microheaters.