Development of non-ionic surfactant vesicles for inhaled drug delivery

  • Mireia Puig

Student thesis: Doctoral Thesis

Abstract

Non-ionic surfactant vesicles (NIVs) provide similar bioavailability as liposomes but they are associated with higher stability profiles and reduced production cost. However, NIVs formulations are limited by the stability of the encapsulated drug and little is know about their use for inhaled delivery. Therefore, in this study, NIVs for pulmonary delivery were developed and factors, which affected their efficacy and stability, were determined. The addition of the cryoprotectant sucrose to NIVs containing amphotericin B (AmB-NIVs) allowed the physicochemical characteristics of the vesicles to be maintained upon freeze-drying and rehydration. Those were proven stable up to 4 months and up to 21 days when reconstituted and stored at 4°C. Pulmonary administration of AmB-NIVs was able to supress the progress of visceral leishmaniasis in vivo with larger particles being superior to smaller sizes (p ≤ 0.05 in the liver and spleen). Incursion of hydroxypropyl-γ-cyclodextrin (HPγCD), rather than sucrose (p ≤ 0.01), protected empty-NIVs when freeze-dried and rehydrated with different drugs. Therefore, empty-NIVs rehydrated with drugs such as cisplatin or gemcitabine, could be formulated in situ evading undesirable drug instability issues. The effect of using different types of vibrating-mesh nebulisers (active and passive) on the stability of AmB-NIVs was determined. AmB-NIVs properties, like drug entrapment efficiency, were not critically impaired upon nebulisation. The NIVs viscosity, the type of drug nebulised and the inhaler used affected the final aerosolised outcome i.e. aerosol output and aerosol droplet size. In vitro screening of novel minor binders (MGBs) against B16 F10 cells and L. donovani identified potential lead compounds. Studies in a murine model of V visceral leishmaniasis showed that intravenous administration of MGB58 encapsulated within NIVs reduced the parasite burdens in the liver (p ≤ 0.05). In conclusion, NIVs have been optimised to provide a stable and successful inhaled drug delivery platform with enhanced bioavailability, especially to target intracellular diseases such as leishmaniasis.
Date of Award13 May 2016
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorKatharine Carter (Supervisor) & Alexander Mullen (Supervisor)

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