Non-ionic surfactant vesicles as a delivery system for cisplatin

Abstract

Cisplatin is a leading anti-cancer drug used in the treatment of various cancers. However, its clinical use is limited by its undesirable toxic side effect profile and the potential of certain tumours to be or to develop resistance to cisplatin. Encapsulation of cisplatin within a vesicular structure such as non-ionic surfactant vesicles (NIVs) was developed to overcome these limitations. Characterisation studies showed that the size and negative surface charge of cisplatin NIVs could be exploited in enhancing their uptake by the mononuclear phagocytic system present in the lungs, liver and spleen. Physicochemical stability of the systems over a 15 month time period was demonstrated in relation to vesicle size and surface charge; the absence of colloidal aggregation and chemical stability of the lipid components. Vesicle entrapment efficiency of cisplatin was improved with increasing cisplatin concentrations used for lipid hydration but subsequent precipitation of drug limited the usefulness of such an approach. Removal of unentrapped cisplatin by the use of diafiltration and resuspension in lower concentrations of cisplatin solution overcame this problem but resulted in drug leakage from the vesicles over time. Preliminary in vitro and in vivo studies were used to evaluate NIVs. In vitro studies confirmed the potential of NIVs in enhancing the anti-cancer effect of cisplatin in comparison to free drug in a murine B16-F0 murine melanoma cell line. In vivo rodent studies compared cisplatin NIVs with free drug solution administered as single doses by intravenous or pulmonary routes of delivery. Intravenous delivery demonstrated more representable results with greater accumulation of cisplatin in the lungs when administered as a NIVs formulation in comparison to free drug solution. In conclusion, NIVs have great potential to be a viable delivery platform for the administration of cisplatin.EThOS - Electronic Theses Online ServiceGBUnited Kingdo