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One of the biggest challenges in infectious disease treatment is the existence of bacterial infections in underskin wound tissue, such as cellulitis. Compared to other treatments, it is harder for antibacterial drugs to penetrate the physical barrier on the affected skin with a nonspecific target, making conventional therapy for cellulitis infection more difficult and considered. In this novel research, we pioneer a combined strategy of dissolving microneedles (MNs) and bacteria-sensitive microparticles (MPs) for enhanced penetration and targeted delivery of chloramphenicol (CHL) to the infection site specifically. The polycaprolactone polymer was used to make MPs because of its sensitivity to bacterial enzyme stimuli. The best microparticle formulation was discovered and optimized using the Design–Expert application. Furthermore, this study evaluated the antibacterial activity of MPs in vitro and in vivo on the mutant Drosophila larval infection model. This strategy shows improvement in the antibacterial activity of MPs and higher retention duration compared to conventional cream formulation, and the inclusion of these MPs into dissolving MNs was able to greatly improve the dermatokinetic characteristics of CHL in ex vivo evaluation. Importantly, the antimicrobial efficacy in an ex vivo infection model demonstrated that, following the use of this strategy, bacterial bioburdens decreased by up to 99.99% after 24 h. The findings offered a proof of concept for the enhancement of CHL dermatokinetic profiles and antimicrobial activities after its preparation into bacteria-sensitive MPs and distribution by MNs. Future research should investigate in vivo effectiveness in an appropriate animal model.

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Globally, the increase of pathogenic bacteria with antibiotic-resistant characteristics has become a critical challenge in medical treatment. The misuse of conventional antibiotics to treat an infectious disease often results in increased resistance and a scarcity of effective antimicrobials to be used in the future against the organisms. Here, we discuss the rise of antimicrobial resistance (AMR) and the need to combat it through the discovery of new synthetic or naturally occurring antibacterial compounds, as well as insights into the application of various drug delivery approaches delivered via various routes compared to conventional delivery systems. AMR-related infectious diseases are also discussed, as is the efficiency of various delivery systems. Future considerations in developing highly effective antimicrobial delivery devices to address antibiotic resistance are also presented here, especially on the smart delivery system of antibiotics.

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