Comparative efficacy, toxicity and biodistribution of the liposomal amphotericin B formulations Fungisome® and AmBisome® in murine cutaneous leishmaniasis

Gert Jan Wijnant, Katrien Van Bocxlaer, Vanessa Yardley, Andy Harris, Mo Alavijeh, Rita Silva-Pedrosa, Sandra Antunes, Isabel Mauricio, Sudaxshina Murdan, Simon L. Croft

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Fungisome® (F), a liposomal amphotericin B (AmB) product, is marketed in India as a safe and effective therapeutic for the parasitic infection visceral leishmaniasis. Its potential in the treatment of cutaneous leishmaniasis (CL), a disfiguring form of the disease affecting the skin, is currently unknown. Here, we report the evaluation of the efficacy of F in the Leishmania major BALB/c murine model of CL, including a head-to-head comparison with the standard liposomal AmB formulation AmBisome® (A). Upon intravenous administration at dose levels of 5, 10 and 15 mg/kg of body weight (on days 0, 2, 4, 6 and 8), F showed clear signs of toxicity (at 15 mg/kg), while A did not. After complete treatment (day 10), the tolerated doses of 5 and 10 mg/kg F had significant antileishmanial activity (ED50 = 4.0 and 12.8 mg/kg for qPCR-based parasite load and lesion size, respectively), although less than that of A at identical doses (ED50 = 3.0 and 8.8 mg/kg). The efficacy of F was inferior compared to A because lower levels of the active agent AmB accumulated within the infected lesion. In conclusion, despite possibly being less safe and efficacious than A at equivalent doses, the moderate in vivo activity of F could indicate a role in the systemic pharmacotherapy of CL.

LanguageEnglish
Pages223-228
Number of pages6
JournalInternational Journal for Parasitology: Drugs and Drug Resistance
Volume8
Issue number2
DOIs
Publication statusPublished - 1 Aug 2018

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Cutaneous Leishmaniasis
Parasite Load
Leishmania major
Parasitic Diseases
Visceral Leishmaniasis
Amphotericin B
Skin Diseases
Intravenous Administration
India
Therapeutics
Body Weight
Drug Therapy
liposomal amphotericin B

Keywords

  • Amphotericin B
  • Cutaneous leishmaniasis
  • Efficacy
  • Liposome
  • Pharmacokinetics

Cite this

Wijnant, Gert Jan ; Van Bocxlaer, Katrien ; Yardley, Vanessa ; Harris, Andy ; Alavijeh, Mo ; Silva-Pedrosa, Rita ; Antunes, Sandra ; Mauricio, Isabel ; Murdan, Sudaxshina ; Croft, Simon L. / Comparative efficacy, toxicity and biodistribution of the liposomal amphotericin B formulations Fungisome® and AmBisome® in murine cutaneous leishmaniasis. In: International Journal for Parasitology: Drugs and Drug Resistance. 2018 ; Vol. 8, No. 2. pp. 223-228.
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Comparative efficacy, toxicity and biodistribution of the liposomal amphotericin B formulations Fungisome® and AmBisome® in murine cutaneous leishmaniasis. / Wijnant, Gert Jan; Van Bocxlaer, Katrien; Yardley, Vanessa; Harris, Andy; Alavijeh, Mo; Silva-Pedrosa, Rita; Antunes, Sandra; Mauricio, Isabel; Murdan, Sudaxshina; Croft, Simon L.

In: International Journal for Parasitology: Drugs and Drug Resistance, Vol. 8, No. 2, 01.08.2018, p. 223-228.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Comparative efficacy, toxicity and biodistribution of the liposomal amphotericin B formulations Fungisome® and AmBisome® in murine cutaneous leishmaniasis

AU - Wijnant, Gert Jan

AU - Van Bocxlaer, Katrien

AU - Yardley, Vanessa

AU - Harris, Andy

AU - Alavijeh, Mo

AU - Silva-Pedrosa, Rita

AU - Antunes, Sandra

AU - Mauricio, Isabel

AU - Murdan, Sudaxshina

AU - Croft, Simon L.

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Y1 - 2018/8/1

N2 - Fungisome® (F), a liposomal amphotericin B (AmB) product, is marketed in India as a safe and effective therapeutic for the parasitic infection visceral leishmaniasis. Its potential in the treatment of cutaneous leishmaniasis (CL), a disfiguring form of the disease affecting the skin, is currently unknown. Here, we report the evaluation of the efficacy of F in the Leishmania major BALB/c murine model of CL, including a head-to-head comparison with the standard liposomal AmB formulation AmBisome® (A). Upon intravenous administration at dose levels of 5, 10 and 15 mg/kg of body weight (on days 0, 2, 4, 6 and 8), F showed clear signs of toxicity (at 15 mg/kg), while A did not. After complete treatment (day 10), the tolerated doses of 5 and 10 mg/kg F had significant antileishmanial activity (ED50 = 4.0 and 12.8 mg/kg for qPCR-based parasite load and lesion size, respectively), although less than that of A at identical doses (ED50 = 3.0 and 8.8 mg/kg). The efficacy of F was inferior compared to A because lower levels of the active agent AmB accumulated within the infected lesion. In conclusion, despite possibly being less safe and efficacious than A at equivalent doses, the moderate in vivo activity of F could indicate a role in the systemic pharmacotherapy of CL.

AB - Fungisome® (F), a liposomal amphotericin B (AmB) product, is marketed in India as a safe and effective therapeutic for the parasitic infection visceral leishmaniasis. Its potential in the treatment of cutaneous leishmaniasis (CL), a disfiguring form of the disease affecting the skin, is currently unknown. Here, we report the evaluation of the efficacy of F in the Leishmania major BALB/c murine model of CL, including a head-to-head comparison with the standard liposomal AmB formulation AmBisome® (A). Upon intravenous administration at dose levels of 5, 10 and 15 mg/kg of body weight (on days 0, 2, 4, 6 and 8), F showed clear signs of toxicity (at 15 mg/kg), while A did not. After complete treatment (day 10), the tolerated doses of 5 and 10 mg/kg F had significant antileishmanial activity (ED50 = 4.0 and 12.8 mg/kg for qPCR-based parasite load and lesion size, respectively), although less than that of A at identical doses (ED50 = 3.0 and 8.8 mg/kg). The efficacy of F was inferior compared to A because lower levels of the active agent AmB accumulated within the infected lesion. In conclusion, despite possibly being less safe and efficacious than A at equivalent doses, the moderate in vivo activity of F could indicate a role in the systemic pharmacotherapy of CL.

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KW - Cutaneous leishmaniasis

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KW - Liposome

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