“Light and drug delivery - based antimicrobial therapies in the fight against infectious disease”

Antibiotic resistance is a global public health crisis. Recently, the U.S. Government released a ″National Action Plan for Combating Antibiotic-Resistant Bacteria 2020-2025 ″, in which it is urged that ″New therapeutics are urgently needed to combat emerging and reemerging antibiotic-resistant pathogens″ [1]. This special issue of Advanced Drug Delivery Reviews focuses on recent breakthroughs in the both the application of novel antimicrobial delivery techniques and the application of light-associated antimicrobial therapies. These approaches have potential for combating the global challenge of antibiotic resistance and in accelerating the next generation of therapies for infectious disease.

With respect to advancing new antimicrobial delivery systems, we focus on new characterization tools and new pharmaceutical material approaches. He et al. demonstrate that artificial intelligence and machine learning can assist drug delivery for effective treatment of infectious diseases [2] while Kuzma et al. review new approaches for visualizing and quantifying antimicrobial drug distribution in tissues [3]. With respect to drug delivery materials approaches, Ropponen et al describe chemical approaches to increase bacterial bioavailability of antibiotics with a specific focus on the gram-negative bacterial barrier [4]; Nwabuife et al. explore the application of liposomal delivery systems against methicillin-resistant staphylococcus aureus [5] and Hu et al. described application and design strategies for GO-based antibacterial composites [6]

Importantly, bacteria that reside in biofilms are particularly recalcitrant towards antimicrobial agents and are a major driver of resistance. Birk et al. review the application of polymeric nano- and microparticulate drug delivery systems for treatment of biofilms [7]; Kasza et al. identify challenges and solutions in polymer drug delivery for bacterial biofilm treatment and discuss a tissue-by-tissue account [8] and Thorn et al. review the innovative approach of enhancing the therapeutic use of biofilm-dispersing enzymes with smart drug delivery systems [9]. Intracellular bacteria and associated infections are another major challenge and breeding ground for resistance, with this focus Subramaniam et al. describe progress in drug delivery strategies for repurposing conventional antibiotics against intracellular infections [10]

Light-associated antimicrobial therapies, such as antimicrobial photodynamic therapy, antimicrobial blue light, and ultraviolet C irradiation, have been investigated as alternative or adjunctive approaches to antibiotics. However, one challenge in the widespread application of light-associated antimicrobial approaches in clinics is the effective delivery of light and associated drugs (e.g., photosensitizers) to different anatomic regions of human body. In this issue, Tuchin et al discussed the principles of tissue optical clearing technology for improving light delivery in human tissues [11]. Tissue optical clearing is based on altering the optical properties of tissue through the introduction of immersion optical clearing agents, which impregnate the tissue of interest. Wang at al outlined the principles and applications of optical waveguides for improved light delivery in human tissues [12]. It was concluded that, when administered via optical waveguides, light-associated antimicrobial therapies can treat both superficial and deep-tissue infections while minimizing off-site effects that afflict conventional pharmacotherapy. Akasov et al reviewed the development of novel nanoparticle-enhanced light therapy as an emerging medical toolkit with multiple applications including antimicrobial therapy [13]. Improved treatment efficacy by combining nanoparticle drug delivery (e.g., photosensitizers and antibiotics) with antimicrobial light has been significantly supported by the literature [14]. Yuan et al discussed various light-activated liposomal drug delivery technology for potential antimicrobial therapies, with emphasis given to repetitive release mechanism and applications of light-activated liposomes [14]. Wang et al presented the enhanced antimicrobial activity through the combination of antimicrobial photodynamic therapy and low-frequency ultrasonic irradiation [15]. Ultrasound irradiation bears a deeper penetration in human tissues than light and, sequentially, can promote drug delivery through the cavitation effect. The biodistribution and pharmacokinetics of antimicrobial drugs are vital to the mechanistic understanding of their efficacy. In this special issue, Kuzma et al outlined the imaging modalities used in visualizing drug distribution with examples ranging from in vitro cellular drug uptake to clinical treatment of microbial infections [16]. Leanse et al updated the findings from numerous studies that capitalize on the antimicrobial effects of antimicrobial blue light, with a focus on the efficacy of antimicrobial blue light against different microbes, identifying endogenous chromophores, and targets of antimicrobial blue light [17]. After reviewing a number of studies, Marasini et al concluded that resistance to light-associated antimicrobial therapies by microorganisms appears unlikely, irrespective of the modality in question, due to the multi-target mode of action [18].

In conclusion, drug delivery system based antimicrobial therapies and light-associated antimicrobial therapies are promising alternative/ or adjunctive approaches to antibiotics against microbial infections. The development of novel light and drug delivery techniques will exert a sustained and powerful influence in advancing this field.

Fig. 1.

of Tuchin VV, Genina EA, Tuchina ES, Svetlakova AV, Svenskaya YI. Optical clearing of tissues: Issues of antimicrobial phototherapy and drug delivery. Adv Drug Deliv Rev 2022; 180:114037.