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

2018-08-01Artigo científico Acesso aberto
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dc.contributor.authorWijnant, Gert Jan
dc.contributor.authorVan Bocxlaer, Katrien
dc.contributor.authorYardley, Vanessa
dc.contributor.authorHarris, Andy
dc.contributor.authorAlavijeh, Mo
dc.contributor.authorSilva-Pedrosa, Rita
dc.contributor.authorAntunes, Sandra
dc.contributor.authorMauricio, Isabel
dc.contributor.authorMurdan, Sudaxshina
dc.contributor.authorCroft, Simon L.
dc.contributor.institutionGlobal Health and Tropical Medicine (GHTM)
dc.contributor.institutionVector borne diseases and pathogens (VBD)
dc.contributor.institutionInstituto de Higiene e Medicina Tropical (IHMT)
dc.contributor.pblElsevier Science Publisher B.V.
dc.date.accessioned2021-05-03T22:37:03Z
dc.date.available2021-05-03T22:37:03Z
dc.date.issued2018-08-01
dc.description.abstractFungisome® (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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent6
dc.format.extent563177
dc.identifier.doi10.1016/j.ijpddr.2018.04.001
dc.identifier.issn2211-3207
dc.identifier.otherPURE: 4053015
dc.identifier.otherPURE UUID: 86c34a2b-cdb3-4e56-b31c-40b52890ceec
dc.identifier.otherScopus: 85045475620
dc.identifier.otherPubMed: 29673889
dc.identifier.otherORCID: /0000-0002-7748-4643/work/49744517
dc.identifier.otherORCID: /0000-0002-5512-9093/work/70243425
dc.identifier.otherWOS: 000438125200008
dc.identifier.urihttp://hdl.handle.net/10362/116842
dc.identifier.urlhttps://www.scopus.com/pages/publications/85045475620
dc.language.isoeng
dc.peerreviewedyes
dc.subjectAmphotericin B
dc.subjectCutaneous leishmaniasis
dc.subjectEfficacy
dc.subjectLiposome
dc.subjectPharmacokinetics
dc.subjectParasitology
dc.subjectInfectious Diseases
dc.subjectPharmacology (medical)
dc.subjectSDG 3 - Good Health and Well-being
dc.titleComparative efficacy, toxicity and biodistribution of the liposomal amphotericin B formulations Fungisome® and AmBisome® in murine cutaneous leishmaniasisen
dc.typejournal article
degois.publication.firstPage223
degois.publication.issue2
degois.publication.lastPage228
degois.publication.titleInternational Journal for Parasitology: Drugs and Drug Resistance
degois.publication.volume8
dspace.entity.typePublication
rcaap.rightsopenAccess

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