Influence of Poly (ethylene glycol) in Cyclosporine A Loaded PVM/MA Nanoparticles and Oral Absorption of the Drug

Cyclosporine A (CsA) has been widely used as a potent immunosuppressive agent in spite of its low oral bioavailability and formulation problems. Thus, we have developed a novel nanoformulation named CsANP-6, containing cyclosporine A associated to poly(methyl vinyl ether-co-maleic) anhydride (PVM/MA) nanoparticles by inclusion of poly(ethylene glycol) 2000 (PEG2000). The new nanoformulation for oral administration presented uniform sizes and zeta potentials for an efficient interaction with the mucosa of the gastrointestinal tract. The addition of PEG2000 to the formulation of PVM/MA nanoparticles increased the efficiency of CsA encapsulation. The release of CsA from CsANP-6 presented the typical biphasic profile of a nanoparticulated system, i.e. a rapid initial release, which could be explained as if a certain amount of CsA remains adsorbed on the surface of the nanoparticles, and then released slowed and steadily. Stability studies of CsANP-6 show that these systems are stable at 5°C up to 1 year. Our results suggest that CsANP-6 can be an alternative to commercial formulations of CsA for oral administration without the adverse effects caused by the vehicle, Cremophor^® EL.