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Open AccessArticle

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

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Department of Pharmacology, Pharmacy and Pharmaceutical Technology, School of Pharmacy. Campus Vida, University of Santiago de Compostela, 15872 Santiago de Compostela, Spain
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Department of Paediatrics, Hospital Clínico Universitario de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), CIBERER, MetabERN, 15706 Santiago de Compostela, Spain
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Skeletal Dysplasia Lab Nemours Biomedical Research Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Road,Wilmington, DE 19803, USA
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Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago de Compostela (IDIS), University Hospital of Santiago de Compostela, Trav. Choupana s/n, 15706 Santiago de Compostela, Spain
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Nasasbiotech, S.L., Canton Grande 3, 15003 A Coruña, Spain
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Department of Morphological Sciences, School of Medicine, Hospital Clínico Universitario de Santiago de Compostela, 15872 Santiago de Compostela, Spain
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Department of Pharmacology, Pharmacy and Pharmaceutical Technology, School of Sciences, Campus de Lugo, University of Santiago de Compostela, 27002 Lugo, Spain
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Authors to whom correspondence should be addressed.
Pharmaceutics 2019, 11(10), 522; https://doi.org/10.3390/pharmaceutics11100522
Received: 31 July 2019 / Revised: 28 September 2019 / Accepted: 3 October 2019 / Published: 11 October 2019
(This article belongs to the Special Issue Nanotechnology-Based Approaches for Chronic Diseases)
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). View Full-Text
Keywords: nanostructured lipid carrier (NLC); lysosomal storage diseases; elosulfase alfa; in vitro cell studies; enzyme activity nanostructured lipid carrier (NLC); lysosomal storage diseases; elosulfase alfa; in vitro cell studies; enzyme activity
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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.

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