Stimuli‐Responsive Release of Antimicrobials Using Hybrid Inorganic Nanoparticle‐Associated Drug‐Delivery Systems

Abstract

Recently, the combination of metallic nanoparticles (NPs) of Au, Ag, Fe2O3, and Fe3O4 with traditional soft matter drug‐delivery systems has emerged as a promising strategy to achieve site‐specific and controlled release of antimicrobial agents. By harnessing the plasmonic and magnetic properties of inorganic NPs, the disruption of antibiotic‐loaded liposomes, polymersomes, and hydrogels can be remotely triggered by mechanisms such as photo‐ and magneto‐thermal effects, microbubble cavitation, magnetic positioning, and pH‐changes, hence offering significant advantages in improving antibacterial efficacy, reducing side effects, and in overcoming antimicrobial resistance. This review highlights the latest development of stimuli‐responsive antibiotic delivery systems incorporating inorganic NPs. The methods employed for preparation of hybrid inorganic NP‐associated drug‐delivery systems and the effects this has upon the system are discussed. Finally, a detailed exposition of the NP‐mediated triggering mechanisms is provided and pertinent examples of their use in antimicrobial applications are presented.

Recent Developments in Antibacterial Therapy: Focus on Stimuli-Responsive Drug-Delivery Systems and Therapeutic Nanoparticles

“…Effort in the development of stimuli-responsive drug-delivery systems has traditionally been focused on the synthesis and modification of biomaterials, such as polymers and lipids, in order to provide them with a wide range of chemical functionalities that readily undergo hydrolysis, enzymatic degradation, or conformational changes in response to either chemical (e.g., pH, ionic strength, reactive oxygen species), physical (e.g., temperature, light, ultrasound ), or biological (e.g., proteolytic enzymes) stimuli and thus induce therapeutic-cargo release. In this regard, the co-formulation of metallic inorganic nanoparticles (NPs) such as Au NPs, Ag NPs, Fe 2 O 3 NPs and Fe 3 O 4 NPs with traditional drug-delivery systems, such as liposomes, polymersomes and hydrogels, is a promising and emerging approach to the stimuli-responsive release of antibiotics [13]. This development is underpinned by the rapid advancements that have been made in the synthesis of monodispersed and biocompatible inorganic NPs with a wide range of surface functionalisation and physicochemical properties.…”

Biodegradable Antibacterial Polymeric Nanosystems: A New Hope to Cope with Multidrug‐Resistant Bacteria

“…This strategy significantly improves the solubility of hydrophobic antibiotics and enhances the antibacterial efficacy to eradicate bacterial infections. More importantly, the de novo synthesized polymers allow the versatile design of the polymeric nanosystems that respond to microenvironment stimuli (e.g., pH, phosphatases, proteases, lipase) from the bacterial infected tissues, and achieve multimodal therapy …”

Bioinspired and Biomimetic Nanotherapies for the Treatment of Infectious Diseases

“…Also, different antibacterial agents can be co-delivered through specific nanocarriers to achieve synergistic effects. In addition to diffusion, release of antibacterial cargoes may be triggered by pathological signals at infection sites, such as pH, reactive oxygen species, and bacterial toxins or lipases (Ladaviere and Gref, 2015; Moorcroft et al, 2018). Compared to free antibacterial agents, drug-loaded antibiotic nanoparticles displayed enhanced drug stability, targeted delivery, prolonged retention, sustained or responsive release, and enhanced penetrating capability.…”