Microneedle liquid injection system assisted delivery of infection responsive nanoparticles: A promising approach for enhanced site-specific delivery of carvacrol against polymicrobial biofilms-infected wounds

Biofilms present a challenge to wound healing and are among the most feared complications through the course of wound management. Carvacrol (CAR) has manifested its antibiofilm potential against multidrug resistant bacterial biofilms. Herein, infection responsive nanoparticles (NPs) of CAR were developed (particle size: 199 ± 8.21 nm and drug load: 1.35 mg/100 µL) and microneedle liquid injection systems (AdminPen®) of various specifications were investigated as delivery devices to achieve the higher concentrations (in contrast to the concentrations delivered through topical hydrogel) of NPs at the target site. The results exhibited an improved biosafety and antibiofilm activity of CAR after encapsulation into the NPs. Ex vivo skin insertion and dermatokinetic studies suggested that AdminPen® 1500 was the most suitable device, as compared to AdminPen® 777 and 1200. Finally, animal studies showed that AdminPen® 1500 delivered around 8.5 times higher concentrations of CAR in the form of NPs as compared with pure CAR from topically applied hydrogel. Moreover, 50% of the delivered NPs from the AdminPen® 1500 were retained at the site of application for 72 h, in contrast to the pure CAR from the hydrogel (5.2% only). Thus, AdminPen® assisted delivery of bacterial enzyme responsive NPs could be an effective approach for enhanced site-specific accumulation of CAR to potentially achieve the prolonged desired antibiofilm effect. However, further in vivo efficacy in a diseased model must now be investigated.