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 (PEG₄₅PCL₁₇) and hydrophilic PEG (PEG₄₅) were utilized as nanocarriers to prepare docetaxel-loaded nanoparticles (DTX/PEG₄₅PCL₁₇ nanoparticles and DTX/PEG₄₅ 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/PEG₄₅ nanoparticles, DTX/PEG₄₅PCL₁₇ nanoparticles showed a smaller mean diameter and better in vitro and in vivo antitumor activity. The cytotoxicity of DTX/PEG₄₅PCL₁₇ nanoparticles against 4T1 cells was 1.31 μg mL^-1, 3.4-fold lower than that of DTX/PEG₄₅ nanoparticles. More importantly, DTX/PEG₄₅PCL₁₇ nanoparticles showed significantly higher antitumor activity in vivo, with an inhibition rate over 80%, 1.5-fold higher than that of DTX/PEG₄₅ 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.