Physicochemical characterization and in vitro biological evaluation of solid compounds from furazolidone-based cyclodextrins for use as leishmanicidal agents

被引:16
作者
Carvalho, Suzana Goncalves [1 ,2 ]
Cipriano, Daniel Fernandes [3 ]
de Freitas, Jair Carlos Checon [3 ]
Junior, Miguel Angelo Schettino [3 ]
Ocaris, Enrique Ronald Yapuchura [3 ]
Teles, Carolina Bioni Garcia [4 ,5 ,6 ]
de Jesus Gouveia, Aurileya [4 ]
Rodrigues, Ricardo Pereira [7 ]
Zanini, Marcos Santos [2 ]
Villanova, Janaina Cecilia Oliveira [2 ,8 ]
机构
[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Drugs & Med, BR-14800903 Araraquara, SP, Brazil
[2] Fed Univ Espirito Santo UFES, Dept Vet Sci, Postgrad Program Vet Sci, BR-29500000 Alegre, ES, Brazil
[3] Fed Univ Espirito Santo UFES, Dept Phys, Lab Carbon & Ceram Mat, BR-29075910 Vitoria, ES, Brazil
[4] Oswaldo Cruz Fdn Rondonia FIOCRUZ, Malaria & Leishmaniasis Bioassay Platform PBML, Porto Velho, Rondonia, Brazil
[5] Biodivers & Biotechnol Bionorte Network, Porto Velho, Rondonia, Brazil
[6] Natl Inst Sci & Technol Epidemiol Western Amazoni, Porto Velho, Rondonia, Brazil
[7] Fed Univ Espirito Santo UFES, Grad Program Pharmaceut Sci, BR-29043900 Vitoria, ES, Brazil
[8] Fed Univ Espirito Santo UFES, Dept Pharm & Nutr, Lab Pharmaceut Prod, BR-29500000 Alegre, ES, Brazil
关键词
beta-Cyclodextrin; 2-Hydroxypropyl-beta-cyclodextrin; Inclusion complexes; Non-complexes; Leishmanicidal activity; X-RAY-DIFFRACTION; BETA-CYCLODEXTRIN; INCLUSION COMPLEXES; STATE NMR; THERMAL-ANALYSIS; ORAL DELIVERY; RAMAN; FORMULATION; 2-HYDROXYPROPYL-BETA-CYCLODEXTRIN; DISPERSIONS;
D O I
10.1007/s13346-020-00841-1
中图分类号
TH7 [仪器、仪表];
学科分类号
0804 ; 080401 ; 081102 ;
摘要
The discovery of new drugs and dosage forms for the treatment of neglected tropical diseases, such as human and animal leishmaniasis, is gaining interest in the chemical, biological, pharmaceutical, and medical fields. Many pharmaceutical companies are exploring the use of old drugs to establishing new drug dosage forms and drug delivery systems, in particular for use in neglected diseases. The formation of complexes with cyclodextrins is widely used to improve the stability, solubility, and bioavailability of pharmaceutical drugs, as well as reduce both the toxicity and side effects of many of these drugs. The aim of this study was to characterize solid compounds obtained from the association between furazolidone (FZD) and beta-cyclodextrin (beta-CD) or hydroxypropyl-beta-cyclodextrin (HP-beta-CD). The solid compounds were prepared in molar ratios of 1:1 and 1:2 (drug:CD) by kneading and lyophilization. Molecular docking was used to predict the preferred relative orientation of FZD when bound in both studied cyclodextrins. The resulting solid compounds were qualitatively characterized by scanning electron microscopy (SEM), thermal analysis (DSC and TG/DTG), X-ray diffraction (XRD), Raman spectroscopy with image mapping (Raman mapping), and(13)C nuclear magnetic resonance spectroscopy (C-13 NMR) in the solid state. The cytotoxicity of the compounds against THP-1 macrophages and the 50% growth inhibition (IC50) againstLeishmania amazonensispromastigote forms were subsequently investigated using in vitro techniques. For all of the solid compounds obtained, the existence of an association between FZD and CD were confirmed by one or more characterization techniques (TG/DTG, DSC, SEM, XRD, RAMAN, and(13)C NMR), particularly by a significant decrease in the crystallinity of these materials and a reduction in the melting enthalpy associated with furazolidone thermal events. The formation of more effective interactions occurred in the compounds prepared by lyophilization, in a 1:2 molar ratio of the two CDs studied. However, the formation of an inclusion complex was confirmed only for the solid compound obtained from HP-beta-CD prepared by lyophilization (LHFZD1:2). The absence of cytotoxicity on the THP-1 macrophage lineages and the leishmanicidal activity were confirmed for all compounds. MHFZD1:2 and LHFZD1:2 were found to be very active against promastigote forms ofL. amazonensis, while all others were considered only active. These results are in line with the literature, demonstrating the existence of biological activity for associations between drugs and CDs in the form of complexes and non-complexes. All solid compounds obtained were found to be promising for use as leishmanicidal agents against promastigote forms ofL. amazonensis.
引用
收藏
页码:1788 / 1809
页数:22
相关论文
共 102 条
[1]   Cellulose I crystallinity determination using FT-Raman spectroscopy: univariate and multivariate methods [J].
Agarwal, Umesh P. ;
Reiner, Richard S. ;
Ralph, Sally A. .
CELLULOSE, 2010, 17 (04) :721-733
[2]   Formulation and advantages of furazolidone in liposomal drug delivery systems [J].
Alam, Muhammad Irfan ;
Paget, Timothy ;
Elkordy, Amal Ali .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2016, 84 :139-145
[3]   Effect of β-cyclodextrin and hydroxypropyl β-cyclodextrin complexation on physicochemical properties and antimicrobial activity of cefdinir [J].
Aleem, Omair ;
Kuchekar, Bhanudas ;
Pore, Yogesh ;
Late, Sameer .
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 2008, 47 (03) :535-540
[4]   Leishmaniasis and poverty [J].
Alvar, Jorge ;
Yactayo, Sergio ;
Bern, Caryn .
TRENDS IN PARASITOLOGY, 2006, 22 (12) :552-557
[5]   Physico-chemical characterization and antibacterial activity of inclusion complexes of Hyptis martiusii Benth essential oil in β-cyclodextrin [J].
Andrade, Tatianny A. ;
Freitas, Thiago S. ;
Araujo, Francielly O. ;
Menezes, Paula P. ;
Doria, Grace Anne A. ;
Rabelo, Alessandra S. ;
Quintans-Junior, Lucindo J. ;
Santos, Marcio R. V. ;
Bezerra, Daniel P. ;
Serafini, Mairim R. ;
Menezes, Irwin Rose A. ;
Nunes, Paula Santos ;
Araujo, Adriano A. S. ;
Costa, Maria S. ;
Campina, Fabia F. ;
Santos, Antonia T. L. ;
Silva, Ana R. P. ;
Coutinho, Henrique D. M. .
BIOMEDICINE & PHARMACOTHERAPY, 2017, 89 :201-207
[6]  
[Anonymous], 2014, PLOS ONE
[7]  
[Anonymous], 2012, Int. J. Pharm. Sci. Rev. Res
[8]  
Araujo MVG, 2007, INCLUSION COMPLEXES, DOI [10.1016/j.bmc.2007.06.013, DOI 10.1016/J.BMC.2007.06.013]
[9]   Elucidating the guest-host interactions and complex formation of praziquantel and cyclodextrin derivatives by 13C and 15N solid-state NMR spectroscopy [J].
Arrua, Eva C. ;
Ferreira, M. Joao G. ;
Salomon, Claudio J. ;
Nunes, Teresa G. .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2015, 496 (02) :812-821
[10]   Drug repositioning: Identifying and developing new uses for existing drugs [J].
Ashburn, TT ;
Thor, KB .
NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (08) :673-683