The efficacy of aerosol treatment with non-ionic surfactant vesicles containing amphotericin B in rodent models of leishmaniasis and pulmonary aspergillosis infection

Manal Alsaadi, Jagdishbhai Laxmanbhai Italia, Alexander Mullen, M.N.V Ravi Kumar, A.A. Candlish, Roderick Williams, C.D. Shaw, Fatima Al-Gawhari, Graham Coombs, Martin Wiese, Alison Thomson, M. Puig-Sellart, J. Wallace, A Sharp, Lee Wheeler, Peter Warn, Katharine Carter

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Amphotericin B (AMB) is used to treat both fungal and leishmanial infections, which are of major significance to human health. Clinical use of free AMB is limited by its nephrotoxicity, whereas liposomal AMB is costly and requires parenteral administration, thus development of novel formulations with enhanced efficacy, minimal toxicity and that can be applied via non-invasive routes is required. In this study we analysed the potential of non-ionic surfactant vesicles (NIV) given by nebulisation to deliver AMB to the lungs, liver and skin. Treatment with AMB-NIV resulted in significantly higher drug levels in the lungs and skin (p < 0.05) compared to similar treatment with AMB solution but significantly lower plasma levels (p < 0.05). Treatment with AMB-NIV resulted in a significant reduction in fungal lung burdens in a rat model of invasive pulmonary aspergillosis (p < 0.05) compared to treatment with the carrier alone. Treatment with AMB-NIV but not AMB solution significantly suppressed Leishmania donovani liver parasite burdens (p < 0.05) but could not inhibit the growth of cutaneous Leishmania major lesions. The results of this study indicate that aerosolised NIV enhanced pulmonary and hepatic delivery whilst minimising systemic exposure and toxicity.
LanguageEnglish
Pages685-691
Number of pages7
JournalJournal of Controlled Release
Volume160
Issue number3
Early online date10 Apr 2012
DOIs
Publication statusPublished - 28 Jun 2012

Fingerprint

Pulmonary Aspergillosis
Leishmaniasis
Amphotericin B
Aerosols
Surface-Active Agents
Rodentia
Infection
Lung
Skin
Liver
Invasive Pulmonary Aspergillosis
Leishmania major
Leishmania donovani
Mycoses
Parasites

Keywords

  • non-ionic surfactant vesicles
  • inhalation
  • amphotericin B
  • Aspergillus
  • Leishmania

Cite this

Alsaadi, Manal ; Italia, Jagdishbhai Laxmanbhai ; Mullen, Alexander ; Kumar, M.N.V Ravi ; Candlish, A.A. ; Williams, Roderick ; Shaw, C.D. ; Al-Gawhari, Fatima ; Coombs, Graham ; Wiese, Martin ; Thomson, Alison ; Puig-Sellart, M. ; Wallace, J. ; Sharp, A ; Wheeler, Lee ; Warn, Peter ; Carter, Katharine. / The efficacy of aerosol treatment with non-ionic surfactant vesicles containing amphotericin B in rodent models of leishmaniasis and pulmonary aspergillosis infection. In: Journal of Controlled Release. 2012 ; Vol. 160, No. 3. pp. 685-691.
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The efficacy of aerosol treatment with non-ionic surfactant vesicles containing amphotericin B in rodent models of leishmaniasis and pulmonary aspergillosis infection. / Alsaadi, Manal; Italia, Jagdishbhai Laxmanbhai; Mullen, Alexander; Kumar, M.N.V Ravi; Candlish, A.A.; Williams, Roderick; Shaw, C.D.; Al-Gawhari, Fatima; Coombs, Graham; Wiese, Martin; Thomson, Alison; Puig-Sellart, M.; Wallace, J.; Sharp, A; Wheeler, Lee; Warn, Peter; Carter, Katharine.

In: Journal of Controlled Release, Vol. 160, No. 3, 28.06.2012, p. 685-691.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The efficacy of aerosol treatment with non-ionic surfactant vesicles containing amphotericin B in rodent models of leishmaniasis and pulmonary aspergillosis infection

AU - Alsaadi, Manal

AU - Italia, Jagdishbhai Laxmanbhai

AU - Mullen, Alexander

AU - Kumar, M.N.V Ravi

AU - Candlish, A.A.

AU - Williams, Roderick

AU - Shaw, C.D.

AU - Al-Gawhari, Fatima

AU - Coombs, Graham

AU - Wiese, Martin

AU - Thomson, Alison

AU - Puig-Sellart, M.

AU - Wallace, J.

AU - Sharp, A

AU - Wheeler, Lee

AU - Warn, Peter

AU - Carter, Katharine

N1 - Copyright © 2012 Elsevier B.V. All rights reserved.

PY - 2012/6/28

Y1 - 2012/6/28

N2 - Amphotericin B (AMB) is used to treat both fungal and leishmanial infections, which are of major significance to human health. Clinical use of free AMB is limited by its nephrotoxicity, whereas liposomal AMB is costly and requires parenteral administration, thus development of novel formulations with enhanced efficacy, minimal toxicity and that can be applied via non-invasive routes is required. In this study we analysed the potential of non-ionic surfactant vesicles (NIV) given by nebulisation to deliver AMB to the lungs, liver and skin. Treatment with AMB-NIV resulted in significantly higher drug levels in the lungs and skin (p < 0.05) compared to similar treatment with AMB solution but significantly lower plasma levels (p < 0.05). Treatment with AMB-NIV resulted in a significant reduction in fungal lung burdens in a rat model of invasive pulmonary aspergillosis (p < 0.05) compared to treatment with the carrier alone. Treatment with AMB-NIV but not AMB solution significantly suppressed Leishmania donovani liver parasite burdens (p < 0.05) but could not inhibit the growth of cutaneous Leishmania major lesions. The results of this study indicate that aerosolised NIV enhanced pulmonary and hepatic delivery whilst minimising systemic exposure and toxicity.

AB - Amphotericin B (AMB) is used to treat both fungal and leishmanial infections, which are of major significance to human health. Clinical use of free AMB is limited by its nephrotoxicity, whereas liposomal AMB is costly and requires parenteral administration, thus development of novel formulations with enhanced efficacy, minimal toxicity and that can be applied via non-invasive routes is required. In this study we analysed the potential of non-ionic surfactant vesicles (NIV) given by nebulisation to deliver AMB to the lungs, liver and skin. Treatment with AMB-NIV resulted in significantly higher drug levels in the lungs and skin (p < 0.05) compared to similar treatment with AMB solution but significantly lower plasma levels (p < 0.05). Treatment with AMB-NIV resulted in a significant reduction in fungal lung burdens in a rat model of invasive pulmonary aspergillosis (p < 0.05) compared to treatment with the carrier alone. Treatment with AMB-NIV but not AMB solution significantly suppressed Leishmania donovani liver parasite burdens (p < 0.05) but could not inhibit the growth of cutaneous Leishmania major lesions. The results of this study indicate that aerosolised NIV enhanced pulmonary and hepatic delivery whilst minimising systemic exposure and toxicity.

KW - non-ionic surfactant vesicles

KW - inhalation

KW - amphotericin B

KW - Aspergillus

KW - Leishmania

U2 - 10.1016/j.jconrel.2012.04.004

DO - 10.1016/j.jconrel.2012.04.004

M3 - Article

VL - 160

SP - 685

EP - 691

JO - Journal of Controlled Release

T2 - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 3

ER -