Saudi Cultural Missions Theses & Dissertations
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Item Restricted Optimization of Antibiotic-Loaded Liposomes for Inhalation to Improve Lung Infection Treatment(Queen's University Belfast, 2025-05) AlHamood, Noura; Vicky, Kett; Deirdre, GilpinCystic fibrosis (CF) and bronchiectasis (BE) are chronic respiratory disorders marked by airway inflammation, mucus obstruction, and recurrent bacterial infections that worsen disease progression. Oral antibiotics, the standard treatment for CF and BE infections, can lead to systemic side effects and antibiotic resistance. Pulmonary delivery of antibiotics offers a localized approach to minimize these issues. Also, inhaled antimicrobial liposomal formulations could offer several advantages over systemic administration, such as enhancing drug concentration directly in the airways, minimizing systemic side effects, and enabling prolonged drug release. This project focuses on manufacturing and optimization of formulations for the pulmonary delivery of apramycin-loaded liposomes in dry powder form with desirable physicochemical characteristics such as: size (< 150 nm), zeta potential (> 50 mV), polydispersity index (PDI) (≤ 0.3), encapsulation efficiency (EE) (>50% ), powder particle sizes (≤ 5 μm), glass transition (Tg) (>50 °C) and water content (≤ 3%) of the final dried powder apramycin products. Initially, Spray-drying parameters were optimized to produce liposomal formulations with small particle size (<150 nm), narrow size distribution (PDI ≤ 0.3), high EE > 50%, positive zeta potential (>30 mV), and respirable particle size (≤5 μm). Subsequently, the composition of the liposomes was optimized to develop an affordable and effective dry powder formulation for pulmonary delivery. The results show that formulation containing D-α tocopherol polyethylene glycol 1000 succinate (TPGS) consistently demonstrated better size and EE compared to those with poloxamer 407, which showed significant size increases post-spray drying. The formulations containing dimethyldioctadecylammonium bromide (DDAB) and TPGS exhibited desirable properties. Stability testing showed that the product remained stable for 24 weeks at 20°C but degraded at higher temperatures of 40 °C with 75 % humidity. Both formulations demonstrated comparable antibacterial efficacy against clinical isolates of Mycobacterium avium complex (MAC) and Pseudomonas aeruginosa (P. aeruginosa), maintaining consistent antimicrobial activity across the isolates. Additionally, the liposomal formulations showed minimal cytotoxicity, with over 80% cell viability at all tested concentrations, confirming their biocompatibility. Reducing the DDAB content to half its amount improved cost-effectiveness while maintaining liposome stability. A freeze-dried formulation was also developed to deliver the liposomes hydrated with apramycin for nebulization. Freeze-drying, with trehalose as a cryoprotectant, minimized water content, preserved a high Tg > 50°C, and enhanced long-term stability. Stability testing of freeze-dried formulations rehydrated into liquid form showed that those stored at 2°C exhibited a low degree of aggregation and performed better than those stored at 20°C. Transitioning from liquid to powder form further improved stability, reducing risks of aggregation and drug leakage. Powder formulations stored at both 2°C and 20°C demonstrated significantly enhanced stability, underscoring their suitability for pulmonary delivery. Finally, this work has demonstrated that inhalable liposomal antibiotic formulations could potentially serve as a novel therapeutic approach for treating lung infections associated with respiratory diseases.15 0Item Restricted Antibiotic Prescribing Practices in Paediatric Hospital-At-Home Care Model A Retrospective Cohort Study(University College London, 2024) Othman, Hassan; Garfield, Sara; Abou Daya, Mohammed; Chambers, PinkieBackground: Paediatric patients at the Royal London Hospital referred to the Hospital-At-Home service mostly receive intravenous antibiotic therapy. However, prescribing practices and the appropriateness of the chosen antibiotics have not been evaluated before. This study evaluated the appropriateness of antibiotics prescribed for those patients. Methods: Patients referred to HAH between 01 August 2023 and 31 January 2024 were screened using a retrospective cohort design. Descriptive analysis was used to analyse the collected data which included biomarkers trends, bio-samples cultured, and evidence of a multi-professional team collaboration. Results: Most patients were neonates aged 28 days or under, 50%. The most common presenting complaint was suspected sepsis (50%). The working diagnosis remained suspected sepsis for 28% of patients while confirmed sepsis in 19%. Also, 17% of patients were diagnosed with viral infections. 79% of participants were reviewed by a clinician before HAH referral, and the advice of an ID consultant was sought by 16%. There was 88% adherence to prescribing guidelines. Only 4.3% of patients were switched to oral antibiotics; however, the switch suitability evaluation suggested that 27.3% of patients were suitable for the switch. Furthermore, the ID consultant recommended stopping or switching to an oral antibiotic for 15% of the chosen patients and potentially discontinuing for 74%. Conclusion: Improvements in antibiotic prescribing practices can be achieved by implementing a robust antimicrobial stewardship program. The active engagement of a multidisciplinary team, comprising a paediatric ID consultant, and pharmacist specialist, is vital in achieving these improvements.31 0Item Restricted Synthesis and Characterization of Fe (III) Complexes of 8- Hydroxyquinolines and Their Antimicrobial Activity against Staphylococcus aureus and Multidrug-Resistant Staphylococcus aureus(Kent State University, 2025-05) Alidrees, Amjad; Songping, HuangThe emergence of multidrug-resistant bacteria, particularly Staphylococcus aureus and Acinetobacter baumannii, presents an urgent need for new antimicrobial strategies. This research focuses on the synthesis and characterization of novel Fe(III) complexes formed with structurally distinct 8-hydroxyquinoline derivatives: 4-methyl-8-hydroxyquinoline, 5-nitro-8-hydroxyquinoline (nitroxoline), and 7-chloro-5-nitro-8-hydroxyquinoline. The complexes were characterized by UV-Vis spectroscopy, FT-IR spectroscopy, elemental analysis, LC-MS, and single-crystal X-ray diffraction. Their antibacterial activity was evaluated against methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA, MRSA), vancomycin-intermediate S. aureus (VISA), and A. baumannii. Minimum inhibitory concentration (MIC) assays, colony-forming unit counts, intracellular reactive oxygen species (ROS) assays, resistance development studies, hemolysis assays, and checkerboard synergy tests were performed. Results demonstrated that the Fe(III) complexes significantly enhanced antibacterial activity compared to free ligands, primarily by disrupting bacterial iron homeostasis and inducing ROS production. The findings offer promising insights into developing Fe(III)-based antimicrobial agents to combat antibiotic-resistant bacterial infections.23 0