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, 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 nanopa