Self-assembled Chitosan-Ceramide Nanoparticle for Enhanced Oral Delivery of Paclitaxel

We aimed to synthesize novel ceramide-chitosan (CS-CE) conjugate that forms stable polymeric nanoparticle capable of functioning as efficient carriers of hydrophobic drug such as Paclitaxel (PTX) for oral delivery. Chitosan (3-5 kDa) was conjugated with ceramide by using a DSC coupling reagent to improve its hydrophobic drug entrapment capacity. The structure of the conjugate was determined by proton (H-1) NMR and FT-IR spectrometry. Size distribution and zeta potential were measured by DLS and PTX content in the cells and plasma was determined by HPLC and LC-MS. Under suitable conditions, the CS-CE self assembled to form colloidally stable nanoparticles with a mean diameter of similar to 300 nm. Further, PTX was incorporated into the CS-CE nanoparticle with 96.9% loading efficiency and 12.1% loading capacity via an emulsion-solvent evaporation method. The PTX-loaded CS-CE (PTX-CS-CE) showed sustained release of PTX and a comparable cytotoxic efficacy to that of free PTX on B16F10 melanoma and MCF-7 human breast adenocarcinoma cell lines. The empty nanoparticles showed no toxicity, indicating that the copolymer is safe to use in drug delivery. In addition, higher cellular uptake and slightly better pharmacokinetic parameters were obtained for PTX-CS-CE nanoparticle compared to free PTX. The polymeric nanoparticle of CS-CE represents a promising nanocarrier of hydrophobic drug for oral delivery.