Preparation and characterization of irinotecan hydrochloride loaded PEO-PPO-PEO micelles and its mechanism of decreasing drug intestinal toxicity

In this work, we developed PEO-PPO-PEO micelles loaded with irinotecan hydrochloride (CPT-11) using breast cancer resistance protein (BCRP) inhibitory material PEO₂₀-PPO₇₀-PEO₂₀, and studied its mechanism of decreasing CPT-11 induced delayed diarrhea and intestinal toxicity.  BCRP-overexpressing MDCKII (MDCKII/BCRP) cells were used to evaluate the effect of PEO₂₀-PPO₇₀-PEO₂₀ and PEO-PPO-PEO micelles on transmembrane transport of CPT-11 in vitro.  The biliary excretion, delayed diarrhea and intestinal damage of CPT-11 loaded PEO-PPO-PEO micelles of rats were investigated.  The results showed that the obtained micelles could decrease the biliary excretion of CPT-11, ameliorate delayed diarrhea and intestinal toxicity of rats through inhibiting BCRP-mediated CPT-11 efflux.  PEO-PPO-PEO micelles were promising carriers to reduce intestinal toxicity of CPTs.