Saudi Cultural Missions Theses & Dissertations
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Item Restricted Development of drug loaded cationic liposomes for pulmonary delivery(Saudi Digital Library, 2023-10-11) Alharbi, Sayer; Kett, VickyThe lower respiratory tract infections (LRTIs) represent a serious threat to human health, especially with the growing prevalence of antimicrobial resistance (AMR). Consequently, the demand for antibiotics with higher activity and better targeting is overwhelmingly increasing. The cationic liposomes composed of dimethyldioctadecylammoniumbromide (DDAB) and soy phosphatidylcholine (SPC) lipids with d-α-tocophyeryl polyethylene glycol succinate (TPGS) as an adjuvant, could have the potential to be effective drug delivery vehicles to deliver antibiotics to the infected sites via the pulmonary route. However, the current liposomal synthesis methods have some disadvantages such as the usage of organic solvents. So, this study aims to investigate an organic solvent free method (OSF) as a potential alternative for the thin film hydration method (TFH) for the preparation of drug loaded liposomes. In addition, this study aims to investigate the effects of DDAB and TPGS contents on the final characteristics of the proposed cationic liposomes formulation. Towards these aims, the hydrophilic apramycin (APR) and the hydrophobic rifampicin (RIF) were used as model drugs. The OSF method encompasses the manual trituration of the lipid components and mixing it with the aqueous phase. The loaded liposomes were characterised for particle size, surface charge, encapsulation efficiency, powder particle size, and thermal properties. The OSF prepared APR-loaded liposomes showed comparable characteristics to the TFH prepared APR-loaded liposomes. However, the RIF-loaded liposomes prepared by the OSF method showed poor characteristics in comparison with the TFH prepared. Indicating the suitability of the OSF method for the synthesis of APR-loaded liposomes and the unsuitability of the method to be used with RIF. These contradicting outcomes were linked to the differences in the aqueous solubility between the two drugs. DDAB and TPGS exerted no effects on the particle size of the liposomes. DDAB showed a proportional relationship with the liposomal surface charge of both drugs, which was linked to the cationic charge of DDAB. TPGS showed no effects on the encapsulation efficiency of APR, while increasing the TPGS content decreased the encapsulation efficiency of RIF. The decrease in RIF encapsulation was attributed to the reduction of the available space for hydrophobic drugs between the lipid bilayers due to the presence of TPGS. This study proposed a solvent free method for the preparation of APR-loaded liposomes, and it contributed to the knowledge about DDAB and TPGS effects on the liposomal formulation. Furthermore, this study recommended the exploration of other solvent free synthesis methods for the preparation of RIF-loaded liposomes.35 0