Cyclosporine A-loaded lipid nanoparticles in inflammatory bowel disease.

Cyclosporine A (CsA) is a well-known immunosuppressive agent used as rescue therapy in severe steroid-refractory ulcerative colitis (UC). However, toxicity issues associated with CsA when administered in its commercially available formulations have been reported in clinical practice. Since nanotechnology has been proposed as a promising strategy to improve safety and efficacy in the treatment of inflammatory bowel disease (IBD), the main purpose of this study was to evaluate the effect of oral administration of CsA-loaded lipid nanoparticles (LN) in the dextran sodium sulfate (DSS)-induced colitis mouse model using Sandimmune Neoral(®) as reference.

Cyclosporine A lipid nanoparticles for oral administration: Pharmacodynamics and safety evaluation.

The pharmacodynamic effect and the safety of cyclosporine A lipid nanoparticles (CsA LN) for oral administration were investigated using Sandimmune Neoral® as reference. First, the biocompatibility of the unloaded LN on Caco-2 cells was demonstrated. The pharmacodynamic response and blood levels of CsA were studied in Balb/c mice after 5 and 10 days of daily oral administration equivalent to 5 and 15 mg/kg of CsA in different formulations.

Reformulating cyclosporine A (CsA): More than just a life cycle management strategy.

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.

Lipid nanoparticles enhance the absorption of cyclosporine A through the gastrointestinal barrier: In vitro and in vivo studies.

In the present work, the feasibility of cyclosporine A lipid nanoparticles (CsA LN) for oral administration was investigated. Three CsA LN formulations were developed using Precirol as lipid matrix, one stabilized with Tween(®) 80 (Tw) and the other two with mixtures of phosphatidylcholine or Pluronic(®) F127 with taurocholate (Lec:TC and PL:TC, respectively). The physical characteristics of the LN were studied under gastrointestinal pH and their integrity was found to be dependent on the stabilizers.

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

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.