Thesis

Non-ionic surfactant vesicles as an Amphotericin B inhaled delivery system for the treatment of leishmaniasis

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Awarding institution
  • University of Strathclyde
Date of award
  • 2013
Thesis identifier
  • T13480
Qualification Level
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Department, School or Faculty
Abstract
  • Amphotericin B (AmB) is a drug used to treat visceral leishmaniasis and fungal infections. Current available AmB formulations are limited by instability at tropical temperature, parenteral administration, renal toxicity (Fungizone®) or cost (AmBisome®, Amphotec® and Abelcet®). In this study, inhaled AmB non-ionic surfactant vesicles (AmB-NIV) were assessed as an alternative AmB formulation, which should reduce costs, enhance drug bioavailability and stability and allow a non-invasive route of administration. AmB-NIV formulations (freshly prepared or lyophilised and non-ultra-filtrated or ultra-filtrated) were characterised on the basis of their vesicle size, ζ-potential, entrapment efficiency and viscosity. High performance liquid chromatography (HPLC) methods were validated and used to quantify the formulation constituents (AmB, cholesterol, surfactant and dicetyl phosphate) in stability studies. AmB-NIV formulations maintained stable at 37oC based on vesicle size, ζ-potential, entrapment efficiency and ingredients concentration up to 28 days. NIV enhanced drug delivery based on in vitro studies using a multi stage liquid impinger (MSLI) and should have lower toxicity based on the aggregation state of AmB. In vivo studies assessing the efficacy of inhaled AmB-NIV into a murine model of visceral leishmaniasis showed that 4 doses of inhaled AmB-NIV significantly reduced liver parasite burdens compared to the controls (p<0.05). Thus, NIV can be used to delivery AmB for the treatment of leishmaniasis by the pulmonary route but a multi-dose regimen is required.
Resource Type
DOI
Date Created
  • 2013
Former identifier
  • 991422

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