RT Journal Article
T1 Enzyme-Loaded Gel Core Nanostructured Lipid Carriers to Improve Treatment of Lysosomal Storage Diseases: Formulation and In Vitro Cellular Studies of Elosulfase Alfa-Loaded Systems
A1 Álvarez González, José Víctor
A1 Herrero Filgueira, Carolina
A1 Fuente González, Alexandre de la
A1 Colón Mejeras, Cristóbal
A1 Beiras Iglesias, Andrés
A1 Tomatsu, Shunji
A1 Blanco Méndez, José
A1 Luzardo Álvarez, Asteria María
A1 Couce Pico, María Luz
A1 Otero Espinar, Francisco Javier
K1 Nanostructured lipid carrier (NLC)
K1 Lysosomal storage diseases
K1 Elosulfase alfa
K1 In vitro cell studies
K1 Enzyme activity
AB Mucopolysaccharidosis IVA (Morquio A) is a rare inherited metabolic disease caused by deficiency of the lysosomal enzyme N-acetylgalatosamine-6- sulfate-sulfatase (GALNS). Until now, treatments employed included hematopoietic stem cell transplantation and enzyme replacement therapy (ERT); the latter being the most commonly used to treat mucopolysaccharidoses, but with serious disadvantages due to rapid degradation and clearance. The purpose of this study was to develop and evaluate the potential of nanostructured lipid carriers (NLCs) by encapsulating elosulfase alfa and preserving its enzyme activity, leading to enhancement of its biological effect in chondrocyte cells. A pegylated elosulfase alfa-loaded NLC was characterized in terms of size, ζ potential, structural lipid composition (DSC and XRD), morphology (TEM microscopy), and stability in human plasma. The final formulation was freeze-dried by selecting the appropriate cryoprotective agent. Viability assays confirmed that NLCs were non-cytotoxic to human fibroblasts. Imaging techniques (confocal and TEM) were used to assess the cellular uptake of NLCs loaded with elosulfase alfa. This study provides evidence that the encapsulated drug exhibits enzyme activity inside the cells. Overall, this study provides a new approach regarding NLCs as a promising delivery system for the encapsulation of elosulfase alfa or other enzymes and the preservation of its activity and stability to be used in enzymatic replacement therapy (ERT).
PB MDPI
YR 2019
FD 2019
LK http://hdl.handle.net/10347/21199
UL http://hdl.handle.net/10347/21199
LA eng
NO Álvarez, J.V.; Herrero Filgueira, C.; González, A.F.; Colón Mejeras, C.; Beiras Iglesias, A.; Tomatsu, S.; Blanco Méndez, J.; Luzardo Álvarez, A.; Couce, M.L.; Otero Espinar, F.J. Enzyme-Loaded Gel Core Nanostructured Lipid Carriers to Improve Treatment of Lysosomal Storage Diseases: Formulation and In Vitro Cellular Studies of Elosulfase Alfa-Loaded Systems. Pharmaceutics 2019, 11, 522
NO This research was funded by Xunta de Galicia, grant number GRC2013/015 and GPC2017/015
DS Minerva
RD 29 abr 2026