Study of benznidazole-cyclodextrin inclusion complexes, cytotoxicity and trypanocidal activity

被引：25

作者：

Lyra, Magaly A. M. ^{[1
]}

Soares-Sobrinho, Jose L. ^{[2
]}

Figueiredo, Regina C. B. Q. ^{[3
]}

Sandes, Jana M. ^{[3
]}

Lima, Adley A. N. ^{[1
,4
]}

Tenorio, Romulo P. ^{[5
]}

Fontes, Danilo A. F. ^{[1
]}

Santos, Fabiana L. A. ^{[1
]}

Rolim, Larissa A. ^{[1
]}

Rolim-Neto, Pedro J. ^{[1
]}

机构：

[1] Univ Fed Pernambuco UFPE, Dept Ciencias Farmaceut, Lab Tecnol Medicamentos, BR-50740521 Recife, PE, Brazil

[2] Univ Fed Piaui, Nucleo Tecnol Farmaceut, BR-64049550 Teresina, PI, Brazil

[3] Fiocruz MS, Ctr Pesquisas Aggeu Magalhaes, Dept Microbiol, BR-50670420 Recife, PE, Brazil

[4] Univ Fed Amazonas, Fac Ciencias Farmaceut, Lab Controle Qualidade Medicamentos, BR-69010330 Manaus, AM, Brazil

[5] Univ Fed Pernambuco UFPE, Programa Posgrad Ciencia Mat, BR-50670901 Recife, PE, Brazil

来源：

JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY | 2012年 / 73卷 / 1-4期

关键词：

Inclusion complex; Stability; Solubility; SOLUBILITY;

D O I：

10.1007/s10847-011-0077-5

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The current chemotherapy for Chagas disease is still based on benznidazole, which has low solubility, but complexation with cyclodextrins provides a way of increasing the solubility. The objective of this work was to characterize the inclusion complexes formed between benznidazole (BNZ) and randomly 2-methyled-beta-cyclodextrin (RM-beta-CD) in aqueous solution and study cytotoxicity and trypanocidal. BNZ:RM-beta-CD solution complex systems were prepared and characterized using the phase solubility diagram, nuclear magnetic resonance and a photostability assays, also to investigate the in vitro trypanocidal activity with epimastigote forms of Trypanossoma cruzi and the study of cytotoxicity against mammal cells. The phase-solubility diagram displayed an A (L)-type feature, providing evidence of the formation of soluble inclusion complexes. The continuous variation method showed the existence of a complex with 1:1 stoichiometry. Toxicity assays demonstrated that inclusion complexes were able to reduce the toxic effects caused by benznidazole alone and that this did not interfere with the trypanocidal activity of the benznidazole. The use of inclusion complexes benznidazole:cyclodextrin is thus a promising alternative for the development of a safe and stable liquid formulation and a new option for the treatment of Chagas disease.

引用

页码：397 / 404

页数：8

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