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

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.

Name dc:type.qualificationname

mres

Level dc:type.qualificationlevel

masters-pg

Grantor dc:publisher.institution

University of Strathclyde

Year dc:date.issued

2013

Author dc:creator

• Puig-Sellart, Mireia

DOI

10.48730/8xfc-j642

Identifier

T13480

OAI identifier oai:identifier

oai:strathclyde:6h440s459