Antibiotic resistance due to suboptimal targeting and inconsistent antibiotic release at bacterial infection sites has driven the formulation of stimuli‐responsive nanocarriers for antibacterial therapy. Unlike conventional nanocarriers, stimuli‐responsive nanocarriers have the ability to specifically enhance targeting and drug release profiles. There has been a significant escalation in the design and development of novel nanomaterials worldwide; in particular, intrinsic stimuli‐responsive antibiotic nanocarriers, due to their enhanced activity, improved targeted delivery, and superior potential for bacterial penetration and eradication. Herein, we provide an extensive and critical review of pH‐, enzyme‐, redox‐, and ionic microenvironment‐responsive nanocarriers that have been reported in literature to date, with an emphasis on the mechanisms of drug release, the nanomaterials used, the nanosystems constructed and the antibacterial efficacy of the nanocarriers. The review also highlights further avenues of research for optimizing their potential and commercialization. This review confirms the potential of intrinsic stimuli‐responsive nanocarriers for enhanced drug delivery and antibacterial killing. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Rampant antimicrobial resistance calls for innovative strategies to effectively control bacterial infections, enhance antibacterial efficacy, minimize side effects, and protect existing antibiotics in the market. Therefore, to enhance the delivery of antibiotics and increase their bioavailability and accumulation at the site of infection, the surfaces of nano-drug delivery systems have been diversely modified. This strategy applies various covalent and non-covalent techniques to introduce specific coating materials that have been found to be effective against various sensitive and resistant microorganisms. In this review, we discuss the techniques of surface modification of nanocarriers loaded with antibacterial agents. Furthermore, saccharides, polymers, peptides, antibiotics, enzymes and cell membranes coatings that have been used for surface functionalization of nano-drug delivery systems are described, emphasizing current approaches for enhancing delivery, bioavailability, and efficacy of surfacemodified antibacterial nanocarriers at infection sites. This article offers a critical overview of the potential of surface-modified antibacterial nanocarriers to overcome the limitations of conventional antibiotics in the treatment of bacterial infections.

Cellular senescence, a hallmark of ageing, contributes to tissue or organ dysfunction and the pathophysiology of diverse age-related diseases (ARD) by various mechanisms. Targeting it by selective elimination of senescent cells (SCs) or blocking senescence-associated secretory phenotypes (SASP) with natural or synthetic compounds has been suggested to improve lifespan. Dietary phytochemicals possess a broad spectrum of biochemical and pharmacological effects that are beneficial to human health. Flavonoids, which are widely consumed in fruits and vegetables worldwide, are emerging as potential therapeutic agents to mitigate senescence. Naringenin, hesperetin, hesperidin, quercetin, fisetin, kaempferol, rutin, apigenin, luteolin, nobiletin, tangeretin, genistein, wogonin, epigallocatechin gallate (EGCG), theaflavin-3-gallate (TF2A), and procyanidin C1 possess potent antisenescence effects. A single biochemical process may not explain their pleiotropic pharmacological impact. Flavonoids directly modulate underlying cellular senescence processes or interact with molecular targets that regulate ageing-related pathways. This review discusses the potential use of flavonoids to mitigate senescence and consequently delay the onset of ageing-related diseases. We also highlight the underlying mechanisms of action of flavonoids as potential senotherapeutics and reflect on future perspectives and possible strategies to optimize and increase the translatability from bench to bedside in senotherapy.

Chronic wound infections caused by antibiotic-resistant bacteria have become a global health concern. This is attributed to the biofilm-forming ability of bacteria on wound surfaces, thus enabling their persistent growth. In most cases, it leads to morbidity and in severe cases mortality. Current conventional approaches used in the treatment of biofilm wounds are proving to be ineffective due to limitations such as the inability to penetrate the biofilm matrix; hence, biofilm-related wounds remain a challenge. Therefore, there is a need for more efficient alternate therapeutic interventions. Hydrogen peroxide (HP) is a known antibacterial/antibiofilm agent; however, prolonged delivery has been challenging due to its short half-life. In this study, we developed a hydrogel for the codelivery of HP and antimicrobial peptides (Ps) against bacteria, biofilms, and wound infection associated with biofilms. The hydrogel was prepared via the Michael addition technique, and the physiochemical properties were characterized. The safety, in vitro , and in vivo antibacterial/antibiofilm activity of the hydrogel was also investigated. Results showed that the hydrogel is biosafe. A greater antibacterial effect was observed with HP-loaded hydrogels (CS-HP; hydrogel loaded with HP and CS-HP-P; hydrogel loaded with HP and peptide) when compared to HP as seen in an approximately twofold and threefold decrease in minimum inhibitory concentration values against methicillin-resistant Staphylococcus aureus (MRSA) bacteria, respectively. Similarly, both the HP-releasing hydrogels showed enhanced antibiofilm activity in the in vivo study in mice models as seen in greater wound closure and enhanced wound healing in histomorphological analysis. Interestingly, the results revealed a synergistic antibacterial/antibiofilm effect between HP and P in both in vitro and in vivo studies. The successfully prepared HP-releasing hydrogels showed the potential to combat bacterial biofilm-related infections and enhance wound healing in mice models. These results suggest that the HP-releasing hydrogels may be a superior platform for eliminating bacterial biofilms without using antibiotics in the treatment of chronic MRSA wound infections, thus improving the quality of human health.

Hyaluronic acid (HA) has become a topic of significant interest in drug delivery research due to its excellent properties, including biosafety, biodegradability, and nonimmunogenicity. Moreover, due to its ease of modification, HA can be used to prepare several HA‐based nanosystems using various approaches. These approaches involve conjugating/grafting of hydrophobic moieties, polyelectrolytes complexation with cationic polymers, or surface modification of various nanoparticles using HA. These nanoparticles are able to selectively deliver antibacterial drugs or diagnostic molecules into the site of infections. In addition, HA can bind with overexpressed cluster of differentiation 44 (CD44) receptors in macrophages and also can be degraded by a family of enzymes called hyaluronidase (HAase) to release drugs or molecules. By binding with these receptors or being degraded at the infection site by HAase, HA‐based nanoparticles allow enhanced and targeted antibacterial delivery. Herein, we present a comprehensive and up‐to‐date review that highlights various techniques of preparation of HA‐based nanoparticles that have been reported in the literature. Furthermore, we also discuss and critically analyze numerous types of HA‐based nanoparticles that have been employed in antibacterial delivery to date. This article offers a critical overview of the potential of HA‐based nanoparticles to overcome the challenges of conventional antibiotics in the treatment of bacterial infections. Moreover, this review identifies further avenues of research for developing multifunctional and biomimetic HA‐based nanoparticles for the treatment, prevention, and/or detection of pathogenic bacteria. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies

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