Folate-polyethyleneimine functionalized mesoporous carbon nanoparticles for enhancing oral bioavailability of paclitaxel

Abstract

Polymer-functionalized carbon nanoparticles hold great promise for their use in enhancing the oral absorption of drugs with poor oral bioavailability. And since the abundant expression of folate receptors in intestinal tract, folic acid (FA) modified uniform mesoporous carbon spheres (UMCS) was used to improve oral absorption of paclitaxel, a chemotherapeutic drug with poor oral bioavailability. In this research, folate-polyethyleneimine (FA-PEI) was grafted onto acid-treated uniform mesoporous carbon spheres through one-step electrostatic attraction. PTX was loaded into mesopores of nanoparticles through solvent evaporation, present as amorphous. The release of PTX from the FA-PEI-UMCS nanoparticles exhibited an initial rapid release, followed by a sustained release. And release rate could be regulated by changing amount of FA-PEI complex on the UMCS. The uptake of PTX-encapsulated nanoparticles was studied exploiting Caco-2 cells as an in vitro model. The results of confocal microscopy and flow cytometry demonstrated that folate functionalization enhanced internalization of nanoparticles by the cells. Moreover, PTX loaded in FA-PEI-UMCS nanoparticles resulted in a 5.37-fold increase in apparent permeability (Papp) across Caco-2 cell monolayers compared to Taxol®. And the in vivo results showed that FA-PEI-UMCS nanoparticles did not only improve the oral bioavailability of PTX, but also decrease the gastrointestinal toxicity of PTX. In conclusion, the FA-PEI-UMCS nanoparticles might be a potentially applicable system to improve oral absorption of drugs with poor oral bioavailability.