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
| Autor: | Couce Ml, Blanco Méndez J, Colón Mejeras C, González Af, Beiras Iglesias A, Otero Espinar Fj, Shunji Tomatsu, Herrero Filgueira C, Luzardo Álvarez A, Álvarez Jv |
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| Přispěvatelé: | Universidade de Santiago de Compostela. Departamento de Ciencias Morfolóxicas, Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica |
| Rok vydání: | 2019 |
| Předmět: |
Drug
media_common.quotation_subject Mucopolysaccharidosis lcsh:RS1-441 Pharmaceutical Science Pharmacology Article Chondrocyte lcsh:Pharmacy and materia medica 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Elosulfase alfa Lysosomal storage diseases medicine Enzyme activity lysosomal storage diseases Nanostructured lipid carrier (NLC) 030304 developmental biology media_common chemistry.chemical_classification 0303 health sciences biology Chemistry Enzyme replacement therapy medicine.disease In vitro Enzyme assay enzyme activity medicine.anatomical_structure Enzyme elosulfase alfa In vitro cell studies nanostructured lipid carrier (NLC) in vitro cell studies biology.protein 030217 neurology & neurosurgery |
| Zdroj: | Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela instname Pharmaceutics Pharmaceutics, Vol 11, Iss 10, p 522 (2019) Volume 11 Issue 10 |
| ISSN: | 1999-4923 |
| Popis: | 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, &zeta 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). |
| Databáze: | OpenAIRE |
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