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Antibiotic-in-Cyclodextrin-in-Liposomes: Formulation Development and Interactions with Model Bacterial Membranes
Kalliopi-Kelli A Vandera1, Pietro Picconi1, Margarita Valero2
1School of Cancer & Pharmaceutical Science, Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, U.K.
Molecular Pharmaceutics
|May 1, 2020
Summary
A novel antibiotic formulation, PPA148, effectively targets Gram-negative bacteria by overcoming their outer membrane defenses. This antibiotic-in-cyclodextrin-in-liposomes (ACL) approach enhances drug delivery and efficacy against challenging infections.
Area of Science:
- Microbiology
- Drug Delivery
- Biophysics
Background:
- Gram-negative bacteria pose significant treatment challenges due to their protective outer membrane.
- Existing antibiotics often struggle to penetrate this barrier, leading to persistent infections.
Purpose of the Study:
- To develop and evaluate a novel drug formulation, PPA148, for enhanced activity against Gram-negative pathogens.
- To investigate the mechanism of action and delivery of the new formulation.
Main Methods:
- Formulation of PPA148 using cyclodextrin complexation and liposomal encapsulation.
- Assessment of antimicrobial activity against ESKAPEE pathogens using Kirby Bauer assay.
- Biophysical techniques including Langmuir trough and neutron reflectivity to study membrane interactions.
Main Results:
- The novel antibiotic-in-cyclodextrin-in-liposomes (ACL) formulation demonstrated increased efficacy against *E. coli* compared to pure PPA148.
- 1 μg of the ACL formulation showed comparable efficacy to 30 μg of pure rifampicin.
- Evidence suggests liposome fusion with the outer membrane and cyclodextrins enhancing inner membrane permeation.
Conclusions:
- The ACL formulation effectively breaches the Gram-negative bacterial cell envelope.
- This novel approach offers a promising strategy to combat antibiotic resistance in Gram-negative infections.
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