Tocopheryl succinate-based lipid nanospheres for paclitaxel delivery: preparation, characters, and in vitro release...

Despite its strong anti-tumor activity against human cancers, paclitaxel (Taxol®) suffers limited clinical applications due to the low aqueous solubility and lack of appropriate delivery vehicles. In an attempt to develop an alternative formulation of paclitaxel suitable for parenteral administration, paclitaxel-loaded lipid nanospheres were constructed as colloidal carrier system for controlled drug delivery. Alpha-tocopheryl succinate (α-TOS), a semi-synthetic vitamin E analog, was employed as a new physiological acceptable lipid material to prepare nanoparticulates. A novel bottom-up process was performed by a modified spontaneous emulsification solvent-diffusion method, which is suitable for large industrial scale production. The influence of key parameters such as temperature and surfactant concentration on the size and uniformity of the distribution of nanospheres were investigated. Spherical particles with ∼100 nm of mean diameter and 90% of drug entrapment efficiency were obtained under optimal conditions. Physicochemical characterization of the particles reveals a molecular dispersion of paclitaxel in the lipidic matrix. The in vitro release behavior of paclitaxel from the developed nanospheres was characterized by an initial fast release, followed by a sustained release up to 72 h. The release mechanism suggests that paclitaxel release from the vehicles was dual controlled by both the diffusion of drug and corrosion of lipid matrix. These results demonstrate the principle suitability of α-TOS-based lipid nanospheres as a potential delivery system for paclitaxel delivery.