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Advanced lactose-based microparticle formulations to treat bacterial infections

Liu, Sai; (2025) Advanced lactose-based microparticle formulations to treat bacterial infections. Doctoral thesis (Ph.D), UCL(University College London).

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Abstract

This thesis investigates the development of lactose-based microparticles for treating bacterial infections, focusing on overcoming antibiotic resistance. Initially, ciprofloxacin (cipro)-loaded lactose microparticles were produced via spray drying to target bacterial lung infections (Chapter 2). These particles exhibited spherical morphology, high cipro loading (96.9%-107.0%), rapid drug release (70%-81% within 5 hours), and effective antibacterial activity against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). However, their aerodynamic performance was suboptimal, with a low fine particle fraction (FPF < 5%) due to aggregation, limiting their potential for deep lung delivery. To address this limitation, electrospraying was explored in Chapter 3 as an alternative production method. The electrosprayed cipro-loaded particles showed improved aerodynamic properties (FPF 5.4%-18.2%) compared to the spray-dried particles, while maintaining spherical morphology and effective antibacterial efficacy. Despite these improvements, aggregation issues persisted, indicating that while electrospraying enhanced some properties, deep lung delivery remained a challenge. This suggested potential for other applications such as treating oral and ear infections. In light of rising antibiotic resistance, Chapter 4 incorporated phage therapy into the lactose microparticles. Phage-loaded electrosprayed particles demonstrated high phage viability (1.5 × 10⁷ PFU/mg) and a rapid burst release of phages (99.0 ± 6.9% within 10 minutes), along with enhanced antibacterial activity against P. aeruginosa compared to pure phage solutions. Although these phage-loaded particles inhibited bacterial growth above a critical concentration, they did not fully eradicate the bacteria over 24 hours. Chapter 5 further advanced this approach by combining cipro and phages within the same microparticle formulation. The resulting dual-loaded particles maintained high phage titer (1.4 × 10⁷ PFU/mg) and efficient cipro loading (0.20 ± 0.01%). The particles exhibited rapid burst release, with 98.8 ± 4.0% of phages and 93.5 ± 7.0% of cipro released within 10 minutes. Moreover, these dual-loaded particles provided sustained bacterial inhibition (over 40 hours at 333 µg/ml), showcasing the potential of combining antibiotics and phages in a single microparticle system. This innovative approach offers a promising strategy for treating bacterial infections, particularly in the oral cavity and outer ear, and addresses the growing challenge of antibiotic resistance.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Advanced lactose-based microparticle formulations to treat bacterial infections
Language: English
Additional information: Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
URI: https://discovery.ucl.ac.uk/id/eprint/10205626
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