Lipid nanoparticles for cyclosporine A administration: development, characterization, and in vitro evaluation of their immunosuppression activity

Melissa Guada,1,2 Victor Sebastián,3,4 Silvia Irusta,3,4 Esperanza Feijoó,1 María del Carmen Dios-Viéitez,1 María José Blanco-Prieto1,2 1Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra,...

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Autores principales:	Guada M, Sebastián V, Irusta S, Feijoó E, Dios-Viéitez MC, Blanco-Prieto MJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/516968162d97414595bea3f5c8c18f62
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spelling	oai:doaj.org-article:516968162d97414595bea3f5c8c18f622021-12-02T03:11:48ZLipid nanoparticles for cyclosporine A administration: development, characterization, and in vitro evaluation of their immunosuppression activity1178-2013https://doaj.org/article/516968162d97414595bea3f5c8c18f622015-10-01T00:00:00Zhttps://www.dovepress.com/lipid-nanoparticles-for-cyclosporine-a-administration-development-char-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Melissa Guada,1,2 Victor Sebastián,3,4 Silvia Irusta,3,4 Esperanza Feijoó,1 María del Carmen Dios-Viéitez,1 María José Blanco-Prieto1,2 1Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, 2Instituto de Investigación Sanitaria de Navarra, IdiSNA, Pamplona, 3Chemical and Environmental Engineering Department and Nanoscience Institute of Aragon, University of Zaragoza, Zaragoza, 4Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Madrid, Spain Abstract: Cyclosporine A (CsA) is an immunosuppressant commonly used in transplantation for prevention of organ rejection as well as in the treatment of several autoimmune disorders. Although commercial formulations are available, they have some stability, bioavailability, and toxicity related problems. Some of these issues are associated with the drug or excipients and others with the dosage forms. With the aim of overcoming these drawbacks, lipid nanoparticles (LN) have been proposed as an alternative, since excipients are biocompatible and also a large amount of surfactants and organic solvents can be avoided. CsA was successfully incorporated into LN using the method of hot homogenization followed by ultrasonication. Three different formulations were optimized for CsA oral administration, using different surfactants: Tween® 80, phosphatidylcholine, taurocholate and Pluronic® F127 (either alone or mixtures). Freshly prepared Precirol nanoparticles showed mean sizes with a narrow size distribution ranging from 121 to 202 nm, and after freeze-drying were between 163 and 270 nm, depending on the stabilizer used. Surface charge was negative in all LN developed. High CsA entrapment efficiency of approximately 100% was achieved. Transmission electron microscopy was used to study the morphology of the optimized LN. Also, the crystallinity of the nanoparticles was studied by X-ray powder diffraction and differential scanning calorimetry. The presence of the drug in LN surfaces was confirmed by X-ray photoelectron spectroscopy. The CsA LN developed preserved their physicochemical properties for 3 months when stored at 4°C. Moreover, when the stabilizer system was composed of two surfactants, the LN formulations were also stable at room temperature. Finally, the new CsA formulations showed in vitro dose-dependent immunosuppressive effects caused by the inhibition of IL-2 levels secreted from stimulated Jurkat cells. The findings obtained in this paper suggest that new lipid nanosystems are a good alternative to produce physicochemically stable CsA formulations for oral administration. Keywords: cyclosporine A, lipid nanoparticles, oral administration, stability, immunosuppressive activity, Jurkat cellsGuada MSebastián VIrusta SFeijoó EDios-Viéitez MCBlanco-Prieto MJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6541-6553 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Guada M Sebastián V Irusta S Feijoó E Dios-Viéitez MC Blanco-Prieto MJ Lipid nanoparticles for cyclosporine A administration: development, characterization, and in vitro evaluation of their immunosuppression activity
description	Melissa Guada,1,2 Victor Sebastián,3,4 Silvia Irusta,3,4 Esperanza Feijoó,1 María del Carmen Dios-Viéitez,1 María José Blanco-Prieto1,2 1Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, 2Instituto de Investigación Sanitaria de Navarra, IdiSNA, Pamplona, 3Chemical and Environmental Engineering Department and Nanoscience Institute of Aragon, University of Zaragoza, Zaragoza, 4Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Madrid, Spain Abstract: Cyclosporine A (CsA) is an immunosuppressant commonly used in transplantation for prevention of organ rejection as well as in the treatment of several autoimmune disorders. Although commercial formulations are available, they have some stability, bioavailability, and toxicity related problems. Some of these issues are associated with the drug or excipients and others with the dosage forms. With the aim of overcoming these drawbacks, lipid nanoparticles (LN) have been proposed as an alternative, since excipients are biocompatible and also a large amount of surfactants and organic solvents can be avoided. CsA was successfully incorporated into LN using the method of hot homogenization followed by ultrasonication. Three different formulations were optimized for CsA oral administration, using different surfactants: Tween® 80, phosphatidylcholine, taurocholate and Pluronic® F127 (either alone or mixtures). Freshly prepared Precirol nanoparticles showed mean sizes with a narrow size distribution ranging from 121 to 202 nm, and after freeze-drying were between 163 and 270 nm, depending on the stabilizer used. Surface charge was negative in all LN developed. High CsA entrapment efficiency of approximately 100% was achieved. Transmission electron microscopy was used to study the morphology of the optimized LN. Also, the crystallinity of the nanoparticles was studied by X-ray powder diffraction and differential scanning calorimetry. The presence of the drug in LN surfaces was confirmed by X-ray photoelectron spectroscopy. The CsA LN developed preserved their physicochemical properties for 3 months when stored at 4°C. Moreover, when the stabilizer system was composed of two surfactants, the LN formulations were also stable at room temperature. Finally, the new CsA formulations showed in vitro dose-dependent immunosuppressive effects caused by the inhibition of IL-2 levels secreted from stimulated Jurkat cells. The findings obtained in this paper suggest that new lipid nanosystems are a good alternative to produce physicochemically stable CsA formulations for oral administration. Keywords: cyclosporine A, lipid nanoparticles, oral administration, stability, immunosuppressive activity, Jurkat cells
format	article
author	Guada M Sebastián V Irusta S Feijoó E Dios-Viéitez MC Blanco-Prieto MJ
author_facet	Guada M Sebastián V Irusta S Feijoó E Dios-Viéitez MC Blanco-Prieto MJ
author_sort	Guada M
title	Lipid nanoparticles for cyclosporine A administration: development, characterization, and in vitro evaluation of their immunosuppression activity
title_short	Lipid nanoparticles for cyclosporine A administration: development, characterization, and in vitro evaluation of their immunosuppression activity
title_full	Lipid nanoparticles for cyclosporine A administration: development, characterization, and in vitro evaluation of their immunosuppression activity
title_fullStr	Lipid nanoparticles for cyclosporine A administration: development, characterization, and in vitro evaluation of their immunosuppression activity
title_full_unstemmed	Lipid nanoparticles for cyclosporine A administration: development, characterization, and in vitro evaluation of their immunosuppression activity
title_sort	lipid nanoparticles for cyclosporine a administration: development, characterization, and in vitro evaluation of their immunosuppression activity
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/516968162d97414595bea3f5c8c18f62
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Lipid nanoparticles for cyclosporine A administration: development, characterization, and in vitro evaluation of their immunosuppression activity

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