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Cyclosporine A (CsA) is a well-known immunosuppressive agent that gained considerable importance in transplant medicine in the late 1970s due to its selective and reversible inhibition of T-lymphocytes. While CsA has been widely used to prevent graft rejection in patients undergoing organ transplant it was also used to treat several systemic and local autoimmune disorders. Currently, the neuro- and cardio-protective effects of CsA (CiCloMulsion®; NeuroSTAT®) are being tested in phase II and III trials respectively and NeuroSTAT® received orphan drug status from US FDA and Europe in 2010. The reformulation strategies focused on developing Cremophor® EL free formulations and address variable bioavailability and toxicity issues of CsA. This review is an attempt to highlight the progress made so far and the room available for further improvements to realize the maximum benefits of CsA.

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

Dos flavonas fueron aisladas del extracto alcohólico de Baccharis nitida (Ruiz et Pavon) Pers., usando técnicas cromatográficas. Estos compuestos fueron caracterizados por métodos espectroscópicos de UV, IR, RMN-1H, RMN-13C, HMQC y EM como 5,7-dihidroxi-6,8,4”™-trimetoxi-flavona (Nevadensina) y 5,4”™-dihidroxi-6,7,8-trimetoxi-flavona (Xantomicrol), aislados por primera vez de esta especie.