Nanoparticles containing β-cyclodextrin potentially useful for the treatment of Niemann-Pick C
Bruna Donida
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Search for more papers by this authorMarco Raabe
Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Search for more papers by this authorBárbara Tauffner
Programa de Pós Graduação em Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Search for more papers by this authorMarcelo A. de Farias
Brazilian Nanotechnology National Laboratory (LNNano), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil
Search for more papers by this authorAndryele Z. Machado
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Search for more papers by this authorFernanda Timm
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Search for more papers by this authorRejane G. Kessler
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Search for more papers by this authorTatiane G. Hammerschmidt
Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Search for more papers by this authorLuiza S. Reinhardt
Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Search for more papers by this authorVerônica B. Brito
Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Departamento de Fisioterapia, Faculdades Integradas de Taquara (FACCAT), Taquara, Brazil
Search for more papers by this authorRodrigo V. Portugal
Brazilian Nanotechnology National Laboratory (LNNano), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil
Search for more papers by this authorAndressa Bernardi
Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil
Search for more papers by this authorRudimar Frozza
Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil
Search for more papers by this authorDinara J. Moura
Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Search for more papers by this authorCorresponding Author
Roberto Giugliani
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Correspondence
Carmen R. Vargas and Roberto Giugliani, Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos Street, 2350, 3rd Floor, Porto Alegre, RS 90035-903, Brazil.
Email: [email protected] (C. R. V), [email protected] (R. G.)
Fernanda Poletto, Department of Organic Chemistry, Institute of Chemistry, Universidade Federal do Rio Grande do Sul, 9500 Avenida Bento Gonçalves, Porto Alegre, RS 91501-970, Brazil.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Fernanda Poletto
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Programa de Pós Graduação em Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Correspondence
Carmen R. Vargas and Roberto Giugliani, Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos Street, 2350, 3rd Floor, Porto Alegre, RS 90035-903, Brazil.
Email: [email protected] (C. R. V), [email protected] (R. G.)
Fernanda Poletto, Department of Organic Chemistry, Institute of Chemistry, Universidade Federal do Rio Grande do Sul, 9500 Avenida Bento Gonçalves, Porto Alegre, RS 91501-970, Brazil.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Carmen R. Vargas
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Correspondence
Carmen R. Vargas and Roberto Giugliani, Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos Street, 2350, 3rd Floor, Porto Alegre, RS 90035-903, Brazil.
Email: [email protected] (C. R. V), [email protected] (R. G.)
Fernanda Poletto, Department of Organic Chemistry, Institute of Chemistry, Universidade Federal do Rio Grande do Sul, 9500 Avenida Bento Gonçalves, Porto Alegre, RS 91501-970, Brazil.
Email: [email protected]
Search for more papers by this authorBruna Donida
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Search for more papers by this authorMarco Raabe
Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Search for more papers by this authorBárbara Tauffner
Programa de Pós Graduação em Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Search for more papers by this authorMarcelo A. de Farias
Brazilian Nanotechnology National Laboratory (LNNano), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil
Search for more papers by this authorAndryele Z. Machado
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Search for more papers by this authorFernanda Timm
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Search for more papers by this authorRejane G. Kessler
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Search for more papers by this authorTatiane G. Hammerschmidt
Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Search for more papers by this authorLuiza S. Reinhardt
Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Search for more papers by this authorVerônica B. Brito
Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Departamento de Fisioterapia, Faculdades Integradas de Taquara (FACCAT), Taquara, Brazil
Search for more papers by this authorRodrigo V. Portugal
Brazilian Nanotechnology National Laboratory (LNNano), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil
Search for more papers by this authorAndressa Bernardi
Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil
Search for more papers by this authorRudimar Frozza
Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil
Search for more papers by this authorDinara J. Moura
Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Search for more papers by this authorCorresponding Author
Roberto Giugliani
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Correspondence
Carmen R. Vargas and Roberto Giugliani, Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos Street, 2350, 3rd Floor, Porto Alegre, RS 90035-903, Brazil.
Email: [email protected] (C. R. V), [email protected] (R. G.)
Fernanda Poletto, Department of Organic Chemistry, Institute of Chemistry, Universidade Federal do Rio Grande do Sul, 9500 Avenida Bento Gonçalves, Porto Alegre, RS 91501-970, Brazil.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Fernanda Poletto
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Programa de Pós Graduação em Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Correspondence
Carmen R. Vargas and Roberto Giugliani, Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos Street, 2350, 3rd Floor, Porto Alegre, RS 90035-903, Brazil.
Email: [email protected] (C. R. V), [email protected] (R. G.)
Fernanda Poletto, Department of Organic Chemistry, Institute of Chemistry, Universidade Federal do Rio Grande do Sul, 9500 Avenida Bento Gonçalves, Porto Alegre, RS 91501-970, Brazil.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Carmen R. Vargas
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Correspondence
Carmen R. Vargas and Roberto Giugliani, Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos Street, 2350, 3rd Floor, Porto Alegre, RS 90035-903, Brazil.
Email: [email protected] (C. R. V), [email protected] (R. G.)
Fernanda Poletto, Department of Organic Chemistry, Institute of Chemistry, Universidade Federal do Rio Grande do Sul, 9500 Avenida Bento Gonçalves, Porto Alegre, RS 91501-970, Brazil.
Email: [email protected]
Search for more papers by this authorFunding information: Conselho Nacional de Desenvolvimento Científico e Tecnológico, Grant/Award Numbers: 141552/2015-8, 401859/2015-0; Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Grant/Award Number: 26/203.195/2016; Fundo de Incentivo à Pesquisa e Eventos, Grant/Award Number: 15-0468; Mercosur Structural Convergence Fund, Grant/Award Number: #03/11
Abstract
β-Cyclodextrin (β-CD) is being considered a promising therapy for Niemann-Pick C (NPC) disease because of its ability to mobilise the entrapped cholesterol from lysosomes, however, a major limitation is its inability to cross the blood-brain barrier (BBB) and address the central nervous system (CNS) manifestations of the disease. Considering this, we aimed to design nanoparticles able to cross the BBB and deliver β-CD into the CNS lysosomes. The physicochemical characteristics of β-CD-loaded nanoparticles were evaluated by dynamic light scattering, small-angle X-ray scattering, and cryogenic transmission electron microscopy. The in vitro analyses were performed with NPC dermal fibroblasts and the β-CD-loaded nanoparticles were tracked in vivo. The nanoparticles showed a mean diameter around 120 nm with a disordered bicontinuous inner structure. The nanoparticles did not cause decrease in cell viability, impairment in the antioxidant enzymes activity, damage to biomolecules or release of reactive species in NPC dermal fibroblasts; also, they did not induce genotoxicity or alter the mitochondrial function in healthy fibroblasts. The β-CD-loaded nanoparticles were taken up by lysosomes reducing the cholesterol accumulated in NPC fibroblasts and reached the CNS of mice more intensely than other organs, demonstrating advantages compared to the free β-CD. The results demonstrated the potential of the β-CD-loaded nanoparticles in reducing the brain impairment of NPC.
CONFLICT OF INTEREST
All authors declare that they have no conflict of interest.
Supporting Information
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