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Title: Colloidal carriers for nebulized drug delivery
Author: Albasarah, Yaqoub Yousif
ISNI:       0000 0004 2721 886X
Awarding Body: University of London
Current Institution: University of London
Date of Award: 2012
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Objectives: To explore the potential of liposomes, chitosan-coated liposomes and chitosan complexes for pulmonary delivery of hydrophilic and hydrophobic materials using medical nebulizers. Methods: Chitosan coated and uncoated liposomal vesicles containing the hydrophobic drug amphotericin B (AmB) or hydrophilic lactate dehydrogenase (LDH) were generated from ethanol-based proliposomes and by thin film hydration. LDH chitosan complexes were prepared using different molecular weights and concentrations of the polymer. The colloidal formulations were assessed for morphology, particle size and surface charge. A twin stage impinger (TSI) was used to determine aerosol deposition following delivery from air-jet, ultrasonic and vibrating-mesh nebulizers. Differential scanning calorimetry (DSC) was used to examine the interaction between some formulation components. Main results: AmB incorporation was highest for vesicles produced from proliposomes. Following nebulization, approximately 60% of the AmB was deposited in the lower stage of TSl. Chitosan-coated and uncoated liposomes had antifungal activities against Candida albicans and Candida tropicalis with a minimum inhibitory concentration of 0.5 mg/ml. The highest molecular weight chitosan had the greatest complex size and a net positive charge of +29.7 mY. Nebulization ofLDH solution resulted in enzyme denaturation and greatly reduced activity. Enzyme stability was improved in liposomal formulations and chitosan complexes compared to LDH in solution with greater than 50% of the LDH in a nebulizer delivered to the lower stage of the TSI, with greater than 60% retained activity. DSC analysis suggested that the interaction between LDH and liposomes was electrostatic, with no penetration into vesicle bilayers. Conclusions: This study has demonstrated the potential of liposomes, chitosan-coated liposomes and chitosan complexes to enhance aerosol delivery of associated materials. Liposomal vesicles of AmB had a high drug-loading that is likely to be effectively delivered to the peripheral airways for treatment of pulmonary fungal infections. Chitosan complexes and liposomes containing LDH provided an effective means of increasing the stability of the labile enzyme to nebulization.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available