Development and characterization of PLGA nanocapsules of grandisin isolated from Virola surinamensis: in vitro release and cytotoxicity studies

The most studied phyto constituent isolated from Virola surinamensis (Rol. ex Rottb.) Warb., Myristicaceae, is the tetrahydrofuran neolignan grandisin, which exhibits a series of biological activities, including trypanocidal, larvicidal and antitumoral. Due to its extremely low solubility, additional studies, including in vivo investigations are challenged by the difficulties in the development of an effective drug delivery system for grandisin. The encapsulation in polymeric nanoparticles is a very attractive alternative for overcoming some of these limitations. In this work, PLGA nanocapsules loaded with grandisin were developed in an attempt to optimize the efficacy of grandisin as an antitumoral drug, with high drug loading and efficiency, prolonged drug release and increased physical-chemical stability. Mean diameter of the nanocapsules was lower than 200 nm, with very low polydispersity. Encapsulation efficiency was above 90%. A sustained in vitro drug release was achieved for up to twenty days and cytotoxicity was markedly increased (IC50 for grandisin-NC and grandisin were 0.005 μM and 0.078 μM, respectively), indicating that polymeric nanocapsules are a potential drug delivery system for grandisin allowing the preparation of formulations viable for further in vivo studies.