Recent Advances in Pharmaceutical Approaches of Antimicrobial Agents for Selective Delivery in Various Administration Routes.

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.

Enhancement in Site-Specific Delivery of Chloramphenicol Using Bacterially Sensitive Microparticle Loaded Into Dissolving Microneedle: Potential For Enhanced Effectiveness Treatment of Cellulitis.

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.

Development of chloramphenicol wound dressing protein-based microparticles in chitosan hydrogel system for improved effectiveness of dermal wound therapy.

Skin wounds have been reported to increase the number of microbial colonies susceptible to infection. Treatments using oral antibiotics have been limited due to their toxicity and hydrophobic characteristics. In this study, we developed a formulation of chloramphenicol microparticles (CPL MPs), which was modified into chitosan hydrogel to increase treatment efficiency in targeting infections and creating an optimal environment to support the healing process. CPL MPs were prepared by a cross-linker stabilized method using whey protein (WPI) biopolymer, and the CPL MPs hydrogel was designed using chitosan biopolymer. Based on the result, CPL-loaded MPs showed desired physical and encapsulation characteristics. In the in vitro study, drug release of CPL MPs in simulated wound fluid represented approximately 99.40 ± 7.01 % of the system after 24 h. The antibacterial activity of CPL-loaded MPs formulation (MIC value 12.5 µg/mL, MBC 25 µg/mL) was effective as MIC concentration increased. Furthermore, the formulation of CPL MPs into hydrogel showed a better dermatokinetic profile compared to hydrogel with pure CPL. Interestingly, the antibacterial activity of the ex vivo infection model showed that Staphylococcus aureus activity decreased by up to 99.98 % after 24 h administration of CPL MPs hydrogel when compared to pure-CPL hydrogel and blank hydrogel. These studies have confirmed that incorporating CPL MPs into hydrogel can provide a promising approach to skin infection treatment.