Influence of Hydrophobic Chains in Nanocarriers on Antitumor Efficacy of Docetaxel Nanoparticles.

The composition of amphiphilic nanocarriers can affect the antitumor efficacy of drug-loaded nanoparticles and should be researched systematically. In this paper, to study the influence of hydrophobic chains, an amphiphilic copolymer (PEGPCL) and hydrophilic PEG (PEG) were utilized as nanocarriers to prepare docetaxel-loaded nanoparticles (DTX/PEGPCL nanoparticles and DTX/PEG nanoparticles) through an antisolvent precipitation method. The two DTX nanoparticles presented a similar drug loading content of approximately 60% and a sheet-like morphology. During the preparation procedure, the drug loading content affected the morphology of DTX nanoparticles, and the nanocarrier composition influenced the particle size. Compared with DTX/PEG nanoparticles, DTX/PEGPCL nanoparticles showed a smaller mean diameter and better in vitro and in vivo antitumor activity. The cytotoxicity of DTX/PEGPCL nanoparticles against 4T1 cells was 1.31 μg mL, 3.4-fold lower than that of DTX/PEG nanoparticles. More importantly, DTX/PEGPCL nanoparticles showed significantly higher antitumor activity in vivo, with an inhibition rate over 80%, 1.5-fold higher than that of DTX/PEG nanoparticles. Based on these results, antitumor activity appears to be significantly affected by the particle size, which was determined by the composition of the nanocarrier. In summary, to improve antitumor efficacy, the amphiphilic structure should be considered and optimized in the design of nanocarriers.