Nanoparticle-Based Drug Delivery Systems for Intracellular Infections

Intracellular infections by pathogens such as Mycobacterium tuberculosis, Salmonella enterica and Brucella spp. represent a major therapeutic challenge owing to limited antibiotic penetration into host cells and rapid microbial evasion. Nanoparticle-based delivery systems overcome these obstacles by enhancing cellular uptake, sustaining release of antimicrobials and directing drugs to infected compartments. Platforms include lipid vesicles, solid lipid nanoparticles, polymeric carriers and inorganic constructs, each offering adjustable size, surface charge, targeting ligands and stimuli-responsive behaviour for controlled drug liberation in acidic, reductive or enzymatic environments. By improving intracellular bioavailability, reducing off-target effects and lowering required doses, these nanoscale vehicles hold promise for oral, inhalational and parenteral administration. Advances in scalable production, biocompatibility assessment and non-invasive imaging are accelerating translation towards clinical use, with potential to curb antimicrobial resistance and address global burdens of chronic and relapsing intracellular infections.

Research from Nature Portfolio

Natural terpene–antibiotic conjugates have been engineered into self-assembling prodrug nanoparticles that deliver penicillin G into infected cells via an environment-sensitive linkage, achieving near-complete eradication of intracellular Staphylococcus aureus. Variations in carrier composition and bond chemistry enable triggered release within phagosomes. Solid lipid nanoparticles loaded with enrofloxacin demonstrate that particle size and surface charge critically influence uptake by macrophages, with larger and more negatively charged carriers achieving up to 37-fold higher intracellular accumulation and prolonged retention, leading to superior clearance of Salmonella. Biodegradable polymeric nanoparticles encapsulating auranofin show sustained release and enhanced localisation at infection sites, producing potent bactericidal effects against Streptococcus pneumoniae and Streptococcus pyogenes, including substantial biofilm disruption and in vivo protection in vertebrate models.

Nanoparticle-Based Drug Delivery Systems for Intracellular Infections publication trend

The graph below shows the total number of articles in nanoparticle-based drug delivery systems for intracellular infections across all publications each year (not limited to Nature Index journals).

Technical terms

Nanoparticle: A carrier with dimensions in the 1–1000 nm range designed for targeted drug delivery.

Liposome: A spherical vesicle with one or more phospholipid bilayers capable of encapsulating both hydrophilic and hydrophobic drugs.

Solid lipid nanoparticle (SLN): A submicron carrier comprising a solid lipid core stabilised by surfactants for controlled release of lipophilic agents.

Polymeric nanocarrier: A biodegradable polymer-based nanoparticle engineered to deliver therapeutics with sustained or stimuli-responsive release.

Stimuli-responsive: Designed to undergo structural or chemical changes in response to environmental triggers such as pH, redox potential or enzymes.

Encapsulation efficiency: The proportion of drug successfully loaded into a carrier relative to the initial amount used in preparation.

References

1. Enhanced intracellular delivery and antibacterial efficacy of enrofloxacin-loaded docosanoic acid solid lipid nanoparticles against intracellular Salmonella. Scientific Reports (2017).
2. Auranofin-loaded nanoparticles as a new therapeutic tool to fight streptococcal infections. Scientific Reports (2016).
3. Self-assembly of H2S-responsive nanoprodrugs based on natural rhein and geraniol for targeted therapy against Salmonella Typhimurium. Journal of Nanobiotechnology (2023).
4. Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections. Molecules (2020).
5. Bioinspired Liposomes for Oral Delivery of Colistin to Combat Intracellular Infections by Salmonella enterica. Advanced Healthcare Materials (2019).