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Published in: Journal of Parasitic Diseases 1/2020

01-03-2020 | Amphotericin B | Original Article

Drug-containing hydrophobic dressings as a topical experimental therapy for cutaneous leishmaniasis

Authors: Viviane Pereira, Neuza Biguinati de Barros, Sharon Rose Aragão Macedo, Amália dos Santos Ferreira, Luiz Alberto Kanis, Roberto Nicolete

Published in: Journal of Parasitic Diseases | Issue 1/2020

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Abstract

Cutaneous leishmaniasis (CL), a clinical condition caused mainly by Leishmania amazonensis in Brazil, is characterized by topical, painless ulcers. The current treatment, based on intravenous administration of pentavalent antimonials, presents low adherence by patients and may cause serious adverse effects, leading to the need for searching new therapeutic options. Thus, this study aimed at evaluating a topical administration of “intelligent dressings” as an alternative treatment for CL. BALB/c mice were infected with L. amazonensis promastigotes. Afterward, lesions were treated with hydrophobic dressings incorporated with clinically used drugs. After lesion development, the following analyses were carried out: measurement of lesion diameters, biochemical analyses of serum, evaluation of the recovery of amastigote forms and histological analyses. No significant clinical changes in serum parameters were observed. The group that was treated with dressings impregnated with Glucantime® displayed the lowest number of amastigotes recovered from tissues (parasite load). Conventional treatment with Glucantime® (i.p.) was also able to reduce parasite load. After 6 weeks from the measurement of the lesions mice treated with dressings impregnated with Pentamidine displayed the smallest values. Representative histological aspects of the lesions showed the absence or few amastigotes inside the macrophages when mice were treated with dressings impregnated with Glucantime® and Pentamidine, respectively. The findings presented here indicate that the topical treatments may constitute an alternative treatment option for CL.
Literature
go back to reference Alkhawajah AM, Larbi E, Al-Gindan Y, Abahussein A, Jain S (1997) Treatment of cutaneous leishmaniasis with antimony: intramuscular versus intralesional administration. Ann Trop Med Parasitol 91(8):899–906CrossRef Alkhawajah AM, Larbi E, Al-Gindan Y, Abahussein A, Jain S (1997) Treatment of cutaneous leishmaniasis with antimony: intramuscular versus intralesional administration. Ann Trop Med Parasitol 91(8):899–906CrossRef
go back to reference Almeida AS, Faleiros ACG, Teixeira DNS, Cota UA, Chica JEL (2008) Valores de referência de parâmetros bioquímicos no sangue de duas linhagens de camundongos. J Bras Patol Med Lab 44(6):429–432CrossRef Almeida AS, Faleiros ACG, Teixeira DNS, Cota UA, Chica JEL (2008) Valores de referência de parâmetros bioquímicos no sangue de duas linhagens de camundongos. J Bras Patol Med Lab 44(6):429–432CrossRef
go back to reference Andrade BB, Boaventura V, Barral-Netto M, Barral A (2005) Métodos diagnósticos da leishmaniose tegumentar: fatos, falácias e perspectivas. Gazeta Médica da Bahia 75(1):75–82 Andrade BB, Boaventura V, Barral-Netto M, Barral A (2005) Métodos diagnósticos da leishmaniose tegumentar: fatos, falácias e perspectivas. Gazeta Médica da Bahia 75(1):75–82
go back to reference Anonymous (2007) BRASIL, Ministério da Saúde. Manual de Vigilância da Leishmaniose Tegumentar Americana, 2nd ed, Brasília Anonymous (2007) BRASIL, Ministério da Saúde. Manual de Vigilância da Leishmaniose Tegumentar Americana, 2nd ed, Brasília
go back to reference Anonymous, WHO - World Health Organization (2010) Control of the leishmaniases: report of a meeting of the WHO Expert Committee on the Control of Leishmaniases. World Health Organization, Geneva Anonymous, WHO - World Health Organization (2010) Control of the leishmaniases: report of a meeting of the WHO Expert Committee on the Control of Leishmaniases. World Health Organization, Geneva
go back to reference Barros NB, Migliaccio V, Facundo VA, Ciancaglini P, Stábeli RG, Nicolete R, Silva-Jardim I (2013) Liposomal-lupane system as alternative chemotherapy against cutaneous leishmaniasis: macrophage as target cell. Exp Parasitol 135:337–343CrossRef Barros NB, Migliaccio V, Facundo VA, Ciancaglini P, Stábeli RG, Nicolete R, Silva-Jardim I (2013) Liposomal-lupane system as alternative chemotherapy against cutaneous leishmaniasis: macrophage as target cell. Exp Parasitol 135:337–343CrossRef
go back to reference Bergonso THD (2007) Valores bioquímicos referenciais de javali (Sus scrofa, Linnaeus, 1758), confinados em fazendas do estado de São Paulo. Dissertation, State University of São Paulo Bergonso THD (2007) Valores bioquímicos referenciais de javali (Sus scrofa, Linnaeus, 1758), confinados em fazendas do estado de São Paulo. Dissertation, State University of São Paulo
go back to reference Berman J (2005) Clinical status of agents being developed for leishmaniasis. Expert Opin Investig Drugs 14(11):1337–1346CrossRef Berman J (2005) Clinical status of agents being developed for leishmaniasis. Expert Opin Investig Drugs 14(11):1337–1346CrossRef
go back to reference Bittencourt AL (2009) Aspectos histopatológicos e ultra-estruturais da leishmaniose cutânea difusa (LCD). Gazeta Médica da Bahia 79(Supl. 3):45–51 Bittencourt AL (2009) Aspectos histopatológicos e ultra-estruturais da leishmaniose cutânea difusa (LCD). Gazeta Médica da Bahia 79(Supl. 3):45–51
go back to reference Carneiro G, Aguiar MG, Fernandes AP, Ferreira LAM (2012) Drug delivery systems for the topical treatment of cutaneous leishmaniasis. Expert Opin Drug Deliv 9(9):1083–1097CrossRef Carneiro G, Aguiar MG, Fernandes AP, Ferreira LAM (2012) Drug delivery systems for the topical treatment of cutaneous leishmaniasis. Expert Opin Drug Deliv 9(9):1083–1097CrossRef
go back to reference Carvalho V, Gomes FSL, Carmo DJ, Batista JA, Viana MN (2006) Planimetria como método para mensuração de feridas. REME 10(4):425–428 Carvalho V, Gomes FSL, Carmo DJ, Batista JA, Viana MN (2006) Planimetria como método para mensuração de feridas. REME 10(4):425–428
go back to reference Celes FS, Trovatti E, Khouri R, Weyenbergh J, Ribeiro SJL, Borges VM, Barud HS, Oliveira CI (2016) DETC-based bacterial cellulose bio-curatives for topical treatment of cutaneous leishmaniasis. Sci Rep 6:38330–38340CrossRef Celes FS, Trovatti E, Khouri R, Weyenbergh J, Ribeiro SJL, Borges VM, Barud HS, Oliveira CI (2016) DETC-based bacterial cellulose bio-curatives for topical treatment of cutaneous leishmaniasis. Sci Rep 6:38330–38340CrossRef
go back to reference Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW, Alvar J, Boelart M (2007) Visceral leishmaniasis: what are the needs for diagnosis, treatment and control. Nat Rev Microbiol 5(11):873–882CrossRef Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW, Alvar J, Boelart M (2007) Visceral leishmaniasis: what are the needs for diagnosis, treatment and control. Nat Rev Microbiol 5(11):873–882CrossRef
go back to reference Costa JML, Saldanha ACR, Nascimento D, Sampaio G, Carneiro F, Lisboa E, Barral A (2009) Modalidades clínicas, diagnóstico e abordagem terapêutica da leishmaniose tegumentar no Brasil. Gaz Méd Bahia 79(Supl. 3):70–83 Costa JML, Saldanha ACR, Nascimento D, Sampaio G, Carneiro F, Lisboa E, Barral A (2009) Modalidades clínicas, diagnóstico e abordagem terapêutica da leishmaniose tegumentar no Brasil. Gaz Méd Bahia 79(Supl. 3):70–83
go back to reference Croft SL, Coombs, Graham H (2003) Leishmaniasis-current chemotherapy and recent advances in the search for novel drugs. Trends Parasitol 19(11):502–508CrossRef Croft SL, Coombs, Graham H (2003) Leishmaniasis-current chemotherapy and recent advances in the search for novel drugs. Trends Parasitol 19(11):502–508CrossRef
go back to reference De Barros NB, Macedo SR, Ferreira AS, Tagliari MP, Kayano AM, Nicolete LDF, Soares AM, Nicolete R (2018) ASP49-phospholipase A 2-loaded liposomes as experimental therapy in cutaneous leishmaniasis model. Int Immunopharmacol 55:128–132CrossRef De Barros NB, Macedo SR, Ferreira AS, Tagliari MP, Kayano AM, Nicolete LDF, Soares AM, Nicolete R (2018) ASP49-phospholipase A 2-loaded liposomes as experimental therapy in cutaneous leishmaniasis model. Int Immunopharmacol 55:128–132CrossRef
go back to reference de Brito MEF, Andrade MS, Dantas-Torres F, Rodrigues EHG, Cavalcanti MDP, Almeida AMPD, Brandão-Filho SP (2012) Cutaneous leishmaniasis in northeastern Brazil: a critical appraisal of studies conducted in State of Pernambuco. Rev Soc Bras Med Trop 45(4):425–429CrossRef de Brito MEF, Andrade MS, Dantas-Torres F, Rodrigues EHG, Cavalcanti MDP, Almeida AMPD, Brandão-Filho SP (2012) Cutaneous leishmaniasis in northeastern Brazil: a critical appraisal of studies conducted in State of Pernambuco. Rev Soc Bras Med Trop 45(4):425–429CrossRef
go back to reference Garnier T, Mäntylä A, Järvinen T, Lawrence MJ, Brown MB, Croft SL (2007) Topical buparvaquone formulations for the treatment of cutaneous leishmaniasis. J Pharm Pharmacol 59(1):41–49CrossRef Garnier T, Mäntylä A, Järvinen T, Lawrence MJ, Brown MB, Croft SL (2007) Topical buparvaquone formulations for the treatment of cutaneous leishmaniasis. J Pharm Pharmacol 59(1):41–49CrossRef
go back to reference Godinho JL et al (2012) Efficacy of miltefosine treatment in Leishmania amazonensis-infected BALB/c mice. Int J Antimicrob Agents 39(4):326–331CrossRef Godinho JL et al (2012) Efficacy of miltefosine treatment in Leishmania amazonensis-infected BALB/c mice. Int J Antimicrob Agents 39(4):326–331CrossRef
go back to reference Kanis LA (2005) Caracterização de filmes de EMA e EMA/PCL-T e aplicação em sistemas de liberação controlada de fármacos. PhD Thesis, Federal University of Santa Catarina Kanis LA (2005) Caracterização de filmes de EMA e EMA/PCL-T e aplicação em sistemas de liberação controlada de fármacos. PhD Thesis, Federal University of Santa Catarina
go back to reference Lima EB, Porto C, Motta JOCD, Sampaio RNR (2007) Tratamento da Leishmaniose Tegumentar Americana/Treatment of American cutaneous leishmaniasis. An Bras Dermatol 82:111–124CrossRef Lima EB, Porto C, Motta JOCD, Sampaio RNR (2007) Tratamento da Leishmaniose Tegumentar Americana/Treatment of American cutaneous leishmaniasis. An Bras Dermatol 82:111–124CrossRef
go back to reference Miguel DC, Yokoyama-Yasunaka JK, Uliana SR (2008) Tamoxifen is effective in the treatment of Leishmania amazonensis infections in mice. PLoS Negl Trop Dis 2(6):e249CrossRef Miguel DC, Yokoyama-Yasunaka JK, Uliana SR (2008) Tamoxifen is effective in the treatment of Leishmania amazonensis infections in mice. PLoS Negl Trop Dis 2(6):e249CrossRef
go back to reference Mincis M, Mincis R (2001) Enzimas hepáticas: aspectos de interesse prático. Rev Bras Med 32(2):56–60 Mincis M, Mincis R (2001) Enzimas hepáticas: aspectos de interesse prático. Rev Bras Med 32(2):56–60
go back to reference Murback NDN, Hans-Filho G, Nascimento RAFD, Nakazato KRDO, Dorval MEMC (2011) American cutaneous leishmaniasis: clinical, epidemiological and laboratory studies conducted at a university teaching hospital in Campo Grande, Mato Grosso do Sul, Brazil. An Bras Dermatol 86(1):55–63CrossRef Murback NDN, Hans-Filho G, Nascimento RAFD, Nakazato KRDO, Dorval MEMC (2011) American cutaneous leishmaniasis: clinical, epidemiological and laboratory studies conducted at a university teaching hospital in Campo Grande, Mato Grosso do Sul, Brazil. An Bras Dermatol 86(1):55–63CrossRef
go back to reference Oliveira MJA (2013) Obtenção de Membranas de Hidrogéis para Tratamento Alternativo da Leishmaniose Tegumentar. PhD Thesis, University of São Paulo Oliveira MJA (2013) Obtenção de Membranas de Hidrogéis para Tratamento Alternativo da Leishmaniose Tegumentar. PhD Thesis, University of São Paulo
go back to reference Oliveira LF, Schubach AO, Martins MM, Passos SL, Oliveira RV, Marzochi MC, Andrade CA (2011) Systematic review of the adverse effects of cutaneous leishmaniasis treatment in the New World. Acta Trop 118(2):87–96CrossRef Oliveira LF, Schubach AO, Martins MM, Passos SL, Oliveira RV, Marzochi MC, Andrade CA (2011) Systematic review of the adverse effects of cutaneous leishmaniasis treatment in the New World. Acta Trop 118(2):87–96CrossRef
go back to reference Pinheiro RO (2004) Leishmaniose tegumentar Americana: mecanismos imunológicos, tratamento e profilaxia. Infarma 16:7–8 Pinheiro RO (2004) Leishmaniose tegumentar Americana: mecanismos imunológicos, tratamento e profilaxia. Infarma 16:7–8
go back to reference Rath S, Rath L, Trivelin LA, Imbrunito TR, Tomazela DM, De Jesús MN, Marzal P (2003) Antimoniais empregados no tratamento da leishmaniose: estado da arte. Quím nova 26(4):550–555CrossRef Rath S, Rath L, Trivelin LA, Imbrunito TR, Tomazela DM, De Jesús MN, Marzal P (2003) Antimoniais empregados no tratamento da leishmaniose: estado da arte. Quím nova 26(4):550–555CrossRef
go back to reference Reveiz L, Maia-Elkhoury ANS, Nicholls RS, Romero GAS, Yadon ZE (2013) Interventions for American cutaneous and mucocutaneous leishmaniasis: a systematic review update. PLoS ONE 8(4):e61843CrossRef Reveiz L, Maia-Elkhoury ANS, Nicholls RS, Romero GAS, Yadon ZE (2013) Interventions for American cutaneous and mucocutaneous leishmaniasis: a systematic review update. PLoS ONE 8(4):e61843CrossRef
go back to reference Silva RE, Toledo Júnior A, Senna MC, Rabello A, Cota G (2016) Intralesional meglumine antimoniate for the treatment of localised cutaneous leishmaniasis: a retrospective review of a Brazilian referral centre. Mem Inst Oswaldo Cruz 111(8):512–516CrossRef Silva RE, Toledo Júnior A, Senna MC, Rabello A, Cota G (2016) Intralesional meglumine antimoniate for the treatment of localised cutaneous leishmaniasis: a retrospective review of a Brazilian referral centre. Mem Inst Oswaldo Cruz 111(8):512–516CrossRef
go back to reference Silveira FT, Müller SR, de Souza AA, Lainson R, Gomes C, Laurenti MD, Corbett CE (2008) Revisão sobre a patogenia da Leishmaniose Tegumentar Americana na Amazônia, com ênfase à doença causada por Leishmania (V.) braziliensis e Leishmania (L.) amazonensis. Revista Paraense de Medicina 22(1):9–20 Silveira FT, Müller SR, de Souza AA, Lainson R, Gomes C, Laurenti MD, Corbett CE (2008) Revisão sobre a patogenia da Leishmaniose Tegumentar Americana na Amazônia, com ênfase à doença causada por Leishmania (V.) braziliensis e Leishmania (L.) amazonensis. Revista Paraense de Medicina 22(1):9–20
go back to reference Solomon M, Pavlotsky F, Leshem E, Ephros M, Trau H, Schwartz E (2011) Liposomal amphotericin B treatment of cutaneous leishmaniasis due to Leishmania tropica. J Eur Acad Dermatol Venereol 25(8):973–977CrossRef Solomon M, Pavlotsky F, Leshem E, Ephros M, Trau H, Schwartz E (2011) Liposomal amphotericin B treatment of cutaneous leishmaniasis due to Leishmania tropica. J Eur Acad Dermatol Venereol 25(8):973–977CrossRef
go back to reference Spinelli MO, Godoy CMSC, Motta MC, Cruz RJ, de Souza JM, Bortolatto J (2012) Perfil bioquímico dos animais de laboratório do biotério da Faculdade de Medicina da USP. Rev Soc Bras Ciên Animais de Laboratório 1(1):76–81 Spinelli MO, Godoy CMSC, Motta MC, Cruz RJ, de Souza JM, Bortolatto J (2012) Perfil bioquímico dos animais de laboratório do biotério da Faculdade de Medicina da USP. Rev Soc Bras Ciên Animais de Laboratório 1(1):76–81
go back to reference Teles CBG, Medeiros JF, dos Santos APA, Freitas LAR, Katsuragawa TH, Cantanhêde LM, Ferreira RGM, Camargo LMA (2015) Molecular characterization of American Cutaneous Leishmaniasis in the Tri-border area of Assis Brasil, Acre State, Brazil. Rev Instit Med Trop São Paulo 57(4):343–347CrossRef Teles CBG, Medeiros JF, dos Santos APA, Freitas LAR, Katsuragawa TH, Cantanhêde LM, Ferreira RGM, Camargo LMA (2015) Molecular characterization of American Cutaneous Leishmaniasis in the Tri-border area of Assis Brasil, Acre State, Brazil. Rev Instit Med Trop São Paulo 57(4):343–347CrossRef
Metadata
Title
Drug-containing hydrophobic dressings as a topical experimental therapy for cutaneous leishmaniasis
Authors
Viviane Pereira
Neuza Biguinati de Barros
Sharon Rose Aragão Macedo
Amália dos Santos Ferreira
Luiz Alberto Kanis
Roberto Nicolete
Publication date
01-03-2020
Publisher
Springer India
Published in
Journal of Parasitic Diseases / Issue 1/2020
Print ISSN: 0971-7196
Electronic ISSN: 0975-0703
DOI
https://doi.org/10.1007/s12639-019-01162-y

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