Oral administration co-delivery nanoparticles of docetaxel and bevacizumab for improving intestinal absorption and enhancing anticancer activity

In this study, to improve the intestinal absorption of small molecule chemotherapeutic drug docetaxel (DTX) and macromolecular monoclonal antibody drug bevacizumab (BVZ), we designed and prepared a type of co-delivery nanoparticles for the oral administration of DTX and BVZ. Carboxymethyl chitosan (CMC) and poly(lactic- co -glycolic acid) (PLGA) were used as the carrier of DTX nanoparticles (CPNP DTX ), and methoxy polyethylene glycol-poly (β-amino ester) (mPEG-PAE) was used as the carrier of BVZ nanoparticles (PPNP BVZ ). Then, the two nanoparticles were physically mixed in mass ratios to form mixed co-delivery nanoparticles, which was named as CPNP DTX &PPNP BVZ . The nanoparticles were characterized with pH-sensitive drug release property. CPNP DTX &PPNP BVZ could significantly increase the bioavailability of DTX and BVZ according to the more cellular uptake in Caco-2 cells and the higher absorption in the intestinal tissue. Compared with free DTX and BVZ, CPNP DTX &PPNP BVZ showed excellent cytotoxic effects on A549 cells. Our study revealed the potential of co-delivery nanoparticles of binary mixture of chemotherapeutic small molecule and macromolecular antibody drug as an oral administration therapeutic system.