Lipid nanoparticles for amphotericin delivery in the treatment of American tegumentary leishmaniasis

Imagem de Miniatura
Arquivos
art_SOUZA_Lipid_nanoparticles_for_amphotericin_delivery_in_the_treatment_2020.PDF (682.57 KB)
Citações na Scopus
8
Tipo de produção
article
Data de publicação
2020
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
SPRINGER HEIDELBERG
Autores
FILIPPIN-MONTEIRO, Fabiola Branco
Citação
DRUG DELIVERY AND TRANSLATIONAL RESEARCH, v.10, n.2, p.403-412, 2020
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Leishmaniasis occurs in the five continents and represents a serious public health challenge, but is still a neglected disease, and the current pharmacological weaponry is far from satisfactory. Triglyceride-rich nanoparticles mimicking chylomicrons (TGNP) behave metabolically like native chylomicrons when injected into the bloodstream. Previously we have shown that TGNP as vehicle to amphothericin B (AB) for treatment of fungi infection showed reduced renal toxicity and lower animal death rates compared to conventional AB. The aim of the current study was to test the tolerability and effectiveness of the TGNP-AB preparation in a murine model of Leishmania amazonensis infection. The in vitro assays determined the cytotoxicity of TGNP-AB, AB, and TGNP in macrophages and promastigote forms and the leishmanicidal activity in infected macrophages. The in vivo toxicity tests were performed in healthy mice with increasing doses of TGPN-AB and AB. Then, animals were treated with 2.5 mg/kg/day of AB, 17.5 mg/kg/day of TGNP-AB, or TGNP three times a week for 4 weeks. TGNP-AB formulation was less cytotoxic for macrophages than AB. TGNP-AB was more effective than AB against the promastigotes forms of the parasite and more effective in reducing the number of infected macrophages and the number of amastigotes forms per cell. TGNP-AB-treated animals showed lower hepatotoxicity. In addition, TGNP-AB group showed a marked reduction in lesion size on the paws and parasitic load. The TGNP-AB preparation attained excellent leishmanicidal activity with remarkable lower drug toxicity at very high doses that, due to the toxicity-buffering properties of the nanocarrier, become fully tolerable.
Palavras-chave
Leishmaniasis treatment, Lipid nanoparticles, Amphotericin, Cholesterol, Nanoemulsions
URI
https://observatorio.fm.usp.br/handle/OPI/35974
Referências
  1. Amato VS, 2011, AM J TROP MED HYG, V85, P818, DOI 10.4269/ajtmh.2011.11-0287
  2. Amato VS, 2007, CLIN INFECT DIS, V44, P311, DOI 10.1086/510494
  3. Aronson N, 2016, CLIN INFECT DIS, V63, P1539, DOI 10.1093/cid/ciw742
  4. BERNARDESSILVA H, 1995, HYPERTENSION, V26, P1207, DOI 10.1161/01.HYP.26.6.1207
  5. Borba EF, 2000, ARTHRITIS RHEUM, V43, P1033, DOI 10.1002/1529-0131(200005)43:5<1033::AID-ANR11>3.0.CO;2-B
  6. Bruni N, 2017, INT J NANOMED, V12, P5289, DOI 10.2147/IJN.S140363
  7. Chavez-Fumagalli MA, 2015, REV SOC BRAS MED TRO, V48, P235, DOI 10.1590/0037-8682-0138-2015
  8. de Camargo RA, 2014, PLOS NEGLECT TROP D, V8, DOI 10.1371/journal.pntd.0003001
  9. de Souza A, 2018, INT J PHARMACEUT, V547, P421, DOI 10.1016/j.ijpharm.2018.06.018
  10. HIRATA MH, 1987, BIOCHIM BIOPHYS ACTA, V917, P344, DOI 10.1016/0005-2760(87)90141-X
  11. Inselmann G, 2002, Eur J Intern Med, V13, P288, DOI 10.1016/S0953-6205(02)00065-1
  12. Kyriakidis I, 2017, EXPERT OPIN DRUG SAF, V16, P149, DOI 10.1080/14740338.2017.1270264
  13. Maranhao RC, 1996, ATHEROSCLEROSIS, V126, P15, DOI 10.1016/0021-9150(96)05889-3
  14. Murray HW, 2005, LANCET, V366, P1561, DOI 10.1016/S0140-6736(05)67629-5
  15. Palma E, 2018, MATERIALS, V11, DOI 10.3390/ma11071167
  16. REDGRAVE TG, 1985, BIOCHIM BIOPHYS ACTA, V835, P104, DOI 10.1016/0005-2760(85)90036-0
  17. Reithinger R, 2007, LANCET INFECT DIS, V7, P581, DOI 10.1016/S1473-3099(07)70209-8
  18. Ribeiro TG, 2014, INT J NANOMED, V9, P877, DOI 10.2147/IJN.S55678
  19. Shaw CD, 2014, NANOMEDICINE-UK, V9, P1531, DOI [10.2217/NNM.14.66, 10.2217/nnm.14.66]
  20. Souza LC, 1999, J ANTIMICROB CHEMOTH, V44, P77, DOI 10.1093/jac/44.1.77
  21. SOUZA LC, 1993, J ANTIMICROB CHEMOTH, V32, P123, DOI 10.1093/jac/32.1.123
  22. Sposito AC, 2004, J AM COLL CARDIOL, V43, P2225, DOI 10.1016/j.jacc.2003.11.065
  23. Sundar S, 2015, EXPERT OPIN PHARMACO, V16, P237, DOI 10.1517/14656566.2015.973850
  24. Tuon FF, 2018, REV INST MED TROP SP, V60, DOI [10.1590/S1678-9946201860071, 10.1590/s1678-9946201860071]
  25. Vinagre CG, 2000, TRANSPLANTATION, V69, P532, DOI 10.1097/00007890-200002270-00012

Coleções
Artigos e Materiais de Revistas Científicas - FM/MIP
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - IMT
Artigos e Materiais de Revistas Científicas - LIM/46
Artigos e Materiais de Revistas Científicas - LIM/48