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Liposomal antimicrobials in the fight against bacterial and fungal pathogens: Clinical successes and development
Hussein T Kenaan1, Ross M Duncan1, Wafa T Al-Jamal1
1School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, UK.
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.
Insights
Liposomal formulations offer a promising strategy to combat escalating antimicrobial resistance by improving drug delivery and reducing toxicity. Overcoming manufacturing challenges is crucial for widespread clinical adoption of these advanced antimicrobial nanomedicines.
Area of Science:
- Nanomedicine
- Drug Delivery
- Antimicrobial Resistance
Background:
- Infectious diseases caused by bacteria, fungi, and protozoa are a growing global health concern, worsened by increasing antimicrobial resistance.
- Current antimicrobial treatments suffer from high toxicity and poor solubility, limiting their effectiveness.
- Liposomal formulations, utilizing lipid bilayers, show significant clinical promise for antimicrobial drug delivery.
Purpose of the Study:
- To review the potential of liposomal formulations in overcoming challenges associated with antimicrobial drug delivery.
- To highlight how liposomes can mitigate toxicity, enhance efficacy, and bypass biological barriers.
- To discuss the need for scalable manufacturing to facilitate clinical translation.
Main Methods:
- Review of existing literature on liposomal drug delivery systems for antimicrobial applications.
- Analysis of marketed liposomal products (e.g., AmBisome®, Arikayce®) and their therapeutic advantages.
- Exploration of strategies for optimizing liposomal composition and structure (e.g., lipid charge, fluidity, PEGylation).
Main Results:
- Liposomes effectively reduce drug toxicity and enhance therapeutic outcomes for infections.
- They can overcome biological barriers like biofilms and the blood-brain barrier.
- Liposomal formulations allow for modulated pharmacokinetics, targeted release, and increased local drug concentrations.
Conclusions:
- Liposomal antimicrobials represent a significant advancement in combating drug-resistant infections.
- Addressing technological and manufacturing hurdles is essential for the successful commercialization and global accessibility of these nanomedicines.
- A shift towards scalable and reproducible manufacturing platforms is necessary to realize the full potential of liposomal antimicrobials.
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