Nanostructured lipid carriers containing benznidazole: physicochemical, biopharmaceutical and cellular in vitro studies

被引：0

作者：

Muraca G. ^{[1
]}

Ruiz M.E. ^{[1
]}

Gambaro R.C. ^{[2
]}

Scioli-Montoto S. ^{[1
]}

Sbaraglini M.L. ^{[1
]}

Padula G. ^{[2
]}

Cisneros J.S. ^{[3
]}

Chain C.Y. ^{[3
]}

Álvarez V.A. ^{[4
]}

Huck-Iriart C. ^{[5
,6
]}

Castro G.R. ^{[7
]}

Piñero M.B. ^{[8
]}

Marchetto M.I. ^{[8
]}

Soto C.A. ^{[8
]}

Islan G.A. ^{[9
]}

Talevi A. ^{[1
]}

机构：

[1] Laboratorio de Investigación y Desarrollo de Bioactivos (LIDeB), Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata

[2] Instituto de Genética Veterinaria (IGEVET, UNLPCONICET La Plata), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata (UNLP), La Plata

[3] Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (CONICET-UNLP), La Plata, Buenos Aires

[4] Grupo de Materiales Compuestos Termoplásticos (CoMP), Instituto de Investigaciones en Ciencia y Tecnología de Materiales (INTEMA), Facultad de Ingeniería, Universidad Nacional de Mar del Plata (UNMDP) – CONICET, Av. Colón 10850, Mar del Plata, Buenos Aires

[5] Laboratorio de Cristalografía Aplicada, Escuela de Ciencia y Tecnología, CONICET, Universidad Nacional de San Martín (UNSAM), Campus Miguelete, 25 de Mayo y Francia, San Martín, Buenos Aires

[6] ALBA Synchrotron Light Source, Carrer de la Llum 2–26, Cerdanyola del Vallès, Barcelona

[7] Nanomedicine Research Unit (Nanomed), Federal University of ABC (UFABC), SP, Santo André

[8] Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Departamento de Microbiología, Facultad de Medicina, Buenos Aires

[9] Centro de Investigación y Desarrollo en Fermentaciones Industriales (CINDEFI), Laboratorio de Nanobiomateriales, Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP)-CONICET (CCT La Plata), Calle 47 y 115, La Plata

来源：

Beilstein Journal of Nanotechnology | 2023年 / 14卷

关键词：

benznidazole; biopharmaceutical study; Chagas disease; nanoparticles; nanostructured lipid carriers; physicochemical characterization; Trypanosoma cruzi;

D O I：

10.3762/BJNANO.14.66

中图分类号：

学科分类号：

摘要：

Chagas disease is a neglected endemic disease prevalent in Latin American countries, affecting around 8 million people. The firstline treatment, benznidazole (BNZ), is effective in the acute stage of the disease but has limited efficacy in the chronic stage, possibly because current treatment regimens do not eradicate transiently dormant Trypanosoma cruzi amastigotes. Nanostructured lipid carriers (NLC) appear to be a promising approach for delivering pharmaceutical active ingredients as they can have a positive impact on bioavailability by modifying the absorption, distribution, and elimination of the drug. In this study, BNZ was successfully loaded into nanocarriers composed of myristyl myristate/Crodamol oil/poloxamer 188 prepared by ultrasonication. A stable NLC formulation was obtained, with ≈80% encapsulation efficiency (%EE) and a biphasic drug release profile with an initial burst release followed by a prolonged phase. The hydrodynamic average diameter and zeta potential of NLC obtained by dynamic light scattering were approximately 150 nm and −13 mV, respectively, while spherical and well-distributed nanoparticles were observed by transmission electron microscopy. Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and small-angle X-ray scattering analyses of the nanoparticles indicated that BNZ might be dispersed in the nanoparticle matrix in an amorphous state. The mean size, zeta potential, polydispersity index, and %EE of the formulation remained stable for at least six months. The hemolytic effect of the nanoparticles was insignificant compared to that of the positive lysis control. The nanoparticle formulation exhibited similar performance in vitro against T. cruzi compared to free BNZ. No formulation-related cytotoxic effects were observed on either Vero or CHO cells. Moreover, BNZ showed a 50% reduction in CHO cell viability at 125 μg/mL, whereas NLC-BNZ and non-loaded NLC did not exert a significant effect on cell viability at the same concentration. These results show potential for the development of new nanomedicines against T. cruzi. © 2023 Muraca et al.; licensee Beilstein-Institut.

引用

页码：804 / 818

页数：14

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