Formulation development and physicochemical characterisation of liposomal antibiotic dry powders for inhaled treatment of chronic respiratory infections

Abstract

Chronic pulmonary infections in cystic fibrosis (CF) and bronchiectasis (BE) are difficult to eradicate due to Pseudomonas aeruginosa (PA) biofilm formation and antibiotic resistance. This study aimed to develop an inhalable liposomal apramycin dry powder formulation to achieve high local drug concentrations in the lungs while minimising systemic toxicity. An organic solvent-free (OSF) method was optimised for liposome manufacture, providing a reproducible and scalable process that avoids solvent residues. The resulting liposomes were spray-dried to obtain powders suitable for dry powder inhaler (DPI) delivery.

Systematic optimisation of process parameters, lipid composition, and drug loading produced formulations with desirable physicochemical characteristics (size < 150 nm, PDI ≤ 0.3, zeta potential > +50 mV, Tg > 50 °C, water ≤ 3%). The optimised 0.5D2T formulation demonstrated favourable aerosolisation performance and stability. In vitro assays showed that liposomal apramycin retained antimicrobial efficacy comparable to free drug against both planktonic and biofilm forms of PA. Confocal microscopy confirmed enhanced liposome–biofilm interaction and distribution. Importantly, the formulations exhibited no cytotoxicity at relevant concentrations.

Overall, the research demonstrates that the OSF method enables the production of stable, spray-dried liposomal apramycin formulations with promising antimicrobial and aerodynamic properties. These findings support the potential of liposomal apramycin DPI as a targeted inhalation therapy for chronic PA infections in people with CF and BE.

Thesis is embargoed until 31 December 2027.

Date of Award	Dec 2025
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Vicky Kett (Supervisor) & Michael Tunney (Supervisor)