(A-19) Near Infrared Light Controlled Release of Antimicrobial Peptide from Microneedle Patches for Treatment of Wound Biofilms

Introduction::
Chronic wounds are often associated with biofilms.¹ The extracellular polymeric substances of biofilms limit diffusion of antimicrobial molecules through the structure and into the biofilm or out to the bulk fluid.^2,3 Herein, we reported a microneedle patch serving as a near infrared light controlled antimicrobial delivery system for the effective treatment of bacterial biofilms.




Materials and Methods::
The polydimethylsiloxane (PDMS) mold was used to prepare an inverse microneedle patch (diameter = 6 mm, density = 150 needles, needle height = 300 μm, diameter of needle base = 300 μm). The 1-tetradecanol (TD)-coated, IR780 and W379 co-loaded poly (vinylpyrrolidone) (PVP) microneedle patches were fabricated as the following procedures.⁴ Fifty μL of a 20% (w/w) PVP aqueous solution containing 25 mg/g W379 antimicrobial peptide and different concentrations of IR780 was deposited into the cavities of the PDMS mold and kept under vacuum for 10 min. Then, the mold was allowed to dry at room temperature. After complete desiccation, the IR780 and W379 co-loaded PVP microneedle patch was carefully separated from the mold. Finally, TD-coated, IR780 and W379 co-loaded PVP microneedle patch was obtained by spraying TD onto the surface of microneedle patch using a commercial Nano spray water compensator for 5 s at room temperature with 10 cm of distance between spray nozzle and patch.




Results, Conclusions, and Discussions::
We successfully obtain TD-coated, W379 and IR780 co-loaded PVP microneedle patches based in the method described above. IR780 in the microneedles served as a NIR light absorbing agent to convert photoenergy to heat, while the TD coating layer served as a switch for controlled releases of W379 peptide due to its phase changing property. Under the NIR irradiation, the TD coating melted, promoting the release of encapsulated W379 peptide from PVP microneedles. The TD-coated, W379 and IR780 co-loaded PVP microneedle patches showed an intermittent release profile corresponding to the NIR light on/off cycle (Figure 1A). The prepared microneedle patches displayed an excellent photothermal responsive antibacterial effect without significant cytotoxicity in vitro (Figure 1B). In addition, by simply controlling the NIR light exposure time, drug release kinetics of microneedle patches can be precisely regulated after insertion into excisional wounds created in human skin tissues ex vivo. These patches also showed high efficacy in combating wound biofilms ex vivo and in vivo. Although the NIR light responsive release of antimicrobial peptide was demonstrated in this study, such microneedle patches could be used to regulate the release of other therapeutic agents (e.g., angiogenic agents and growth factors) as well for promoting wound healing.




Conclusions: We have demonstrated the fabrication of TD-coated, W379 and IR780 co-loaded PVP microneedle patches through the molding and spray coating. such an NIR light responsive microneedle-based drug delivery system could provide a platform technology for controlled release of antimicrobial agents and growth factors for combating biofilms and promoting wound healing.


We have demonstrated the fabrication of TD-coated, W379 and IR780 co-loaded PVP microneedle patches through the molding and spray coating. such an NIR light responsive microneedle-based drug delivery system could provide a platform technology for controlled release of antimicrobial agents and growth factors for combating biofilms and promoting wound healing.




Acknowledgements (Optional): :
This work was partially supported by startup funds from University of Nebraska Medical Center (UNMC), UNMC Regenerative Medicine Program pilot grant, National Institute of General Medical Science (NIGMS) of the National Institutes of Health (NIH) under Award Numbers R01GM123081 and R01GM138552.




References (Optional): :
1) Su Y et al., Mol. Pharm. 2019, 16, 2011-2020. 2) Su Y et al., ACS Nano 2020, 14, 11775-11786; 3) Su et al., Adv. Healthcare Mater. 2021, 10, 2100135. 4) Su et al., J. Controlled Rel. 2023, 356, 131-141.