Nanostructured Lipid Carriers Loaded with Dexamethasone Prevent Inflammatory Responses in Primary Non-Parenchymal Liver Cells
Carolina Medina-Montano,
Ignacio Rivero Berti,
Rocío C. Gambaro,
María José Limeres,
Malin Svensson,
Gisel Padula,
Cecilia Y. Chain,
José Sebastián Cisneros,
Guillermo R. Castro,
Stephan Grabbe,
Matthias Bros,
Stephan Gehring,
German A. Islan,
Maximiliano L. Cacicedo
Affiliations
Carolina Medina-Montano
Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
Ignacio Rivero Berti
Laboratorio de Nanobiomateriales, Centro de Investigación y Desarrollo en Fermentaciones Industriales (CINDEFI), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP)-CONICET (CCT La Plata), Calle 47 y 115, La Plata B1900, Argentina
Rocío C. Gambaro
Instituto de Genética Veterinaria (IGEVET, UNLP-CONICET La Plata), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata (UNLP), La Plata B1900, Argentina
María José Limeres
Children’s Hospital, University Medical Center of the Johannes-Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany
Malin Svensson
Children’s Hospital, University Medical Center of the Johannes-Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany
Gisel Padula
Instituto de Genética Veterinaria (IGEVET, UNLP-CONICET La Plata), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata (UNLP), La Plata B1900, Argentina
Cecilia Y. Chain
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (CONICET-UNLP), La Plata B1900, Argentina
José Sebastián Cisneros
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (CONICET-UNLP), La Plata B1900, Argentina
Guillermo R. Castro
Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC), Partner Laboratory of the Max Planck Institute for Biophysical Chemistry (MPIbpC, MPG), Centro de Estudios Interdisciplinarios (CEI), Universidad Nacional de Rosario, Maipú 1065, Rosario S2000, Argentina
Stephan Grabbe
Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
Matthias Bros
Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
Stephan Gehring
Children’s Hospital, University Medical Center of the Johannes-Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany
German A. Islan
Laboratorio de Nanobiomateriales, Centro de Investigación y Desarrollo en Fermentaciones Industriales (CINDEFI), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP)-CONICET (CCT La Plata), Calle 47 y 115, La Plata B1900, Argentina
Maximiliano L. Cacicedo
Children’s Hospital, University Medical Center of the Johannes-Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany
Liver inflammation represents a major clinical problem in a wide range of pathologies. Among the strategies to prevent liver failure, dexamethasone (DXM) has been widely used to suppress inflammatory responses. The use of nanocarriers for encapsulation and sustained release of glucocorticoids to liver cells could provide a solution to prevent severe side effects associated with systemic delivery as the conventional treatment regime. Here we describe a nanostructured lipid carrier developed to efficiently encapsulate and release DXM. This nano-formulation proved to be stable over time, did not interact in vitro with plasma opsonins, and was well tolerated by primary non-parenchymal liver cells (NPCs). Released DXM preserved its pharmacological activity, as evidenced by inducing robust anti-inflammatory responses in NPCs. Taken together, nanostructured lipid carriers may constitute a reliable platform for the delivery of DXM to treat pathologies associated with chronic liver inflammation.
