# Liposomal antimicrobials in the fight against bacterial and fungal pathogens: Clinical successes and development challenges

## TL;DR

Liposomal antimicrobials show promise in reducing toxicity and improving treatment of bacterial and fungal infections, but require scalable manufacturing for global access.

## Contribution

The paper advocates for simplified liposomal formulation design and scalable manufacturing to address antimicrobial resistance and improve accessibility.

## Key findings

- Liposomal formulations like AmBisome® and Arikayce® reduce toxicity and enhance drug efficacy.
- Adjustments in liposomal composition can improve therapeutic outcomes for antimicrobial treatments.
- Scalable and cost-effective manufacturing is critical for the widespread adoption of liposomal antimicrobials.

## Abstract

Bacterial, fungal, and protozoan infections pose a rapidly escalating threat to global health, exacerbated by the rise in antimicrobial resistance. Current therapies against microbial pathogens are limited by high systemic toxicity and poor drug solubility. Liposomal formulations (spherical vesicles composed of lipid bilayers) have demonstrated remarkable clinical potential in addressing these concerns, as evidenced by the marketed products AmBisome® and Arikayce®. These products, which deliver amphotericin B via parenteral injection and amikacin via inhalation, exemplify how liposomes effectively mitigate drug-associated toxicity, enhance therapeutic efficacy, and overcome the biological barriers inherent to infection sites, including complex microbial biofilms, mucosal interfaces, or the blood–brain barrier. Complementary insights from anticancer research indicate that strategic manipulation of liposomal composition and structure can enhance their therapeutic potential. Adjustments in lipid charge, fluidity, and PEGylation, in particular, highlight their versatility and broad applicability for antimicrobial drug delivery. Liposomal antimicrobials can modulate pharmacokinetic profiles, achieve targeted release at sites of infection, and increase local drug concentrations, which are key advantages over conventional treatments. Despite these therapeutic advances, successful clinical translation and widespread adoption of liposomal antimicrobials remain highly dependent on overcoming existing technological and manufacturing challenges. This review emphasises the need for a paradigm shift within liposomal antimicrobial development, encouraging progression from initial research and development toward scalable, reproducible, and economically viable commercial manufacturing platforms. This transition is essential not only for ensuring the global accessibility and affordability of existing therapies but also for expanding the development of clinically relevant liposomal antimicrobial nanomedicines.

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•Liposomal antimicrobials can reduce the toxicity and enhance efficacy against bacterial and fungal infections through barrier penetration and extended release.•We advocate for simple liposomal formulation design and scalable manufacturing technologies to ensure affordable global access and to accelerate progress in curbing AMR.

Liposomal antimicrobials can reduce the toxicity and enhance efficacy against bacterial and fungal infections through barrier penetration and extended release.

We advocate for simple liposomal formulation design and scalable manufacturing technologies to ensure affordable global access and to accelerate progress in curbing AMR.