Investigation of the release behavior of DEHP from infusion sets by paclitaxel-loaded polymeric micelles

The current clinical formulation of paclitaxel (Taxol®) contains 1:1 blend of Cremophor® EL (polyethoxylated castor oil) and dehydrated ethanol. Cremophor® EL and dehydrated ethanol are well known to leach di-(2-ethylhexyl) phthalate (DEHP) from polyvinyl chloride (PVC) infusion bags and PVC administration sets. DEHP is a possible hepatotoxin, carcinogen, teratogen and mutagen. Long-term exposure to DEHP may cause health risks. As an alternative formulation for paclitaxel, paclitaxel-loaded polymeric micelles (PLPM), made of monomethoxy poly(ethylene glycol)-block-poly(d,l-lactide) (mPEG-PDLLA) diblock copolymer, has demonstrated clear advantages over Taxol® in pharmacokinetics and therapeutic index. Paclitaxel in either PLPM or Taxol® formulations, diluted in 0.9% sodium chloride injection, was stable in the PVC infusion bags. The PLPM formulation significantly reduced the amount of DEHP extracted from PVC infusion bags and PVC administration sets. For PLPM diluted in 0.9% sodium chloride injection, the total amount of DEHP delivered over the simulated infusion period was 0.7 mg for 3 h and 2.0 mg for 24 h, which was less than 2.9% of the DEHP extracted by Taxol®. These results confirmed that there is negligible risk of DEHP exposure from diluted PLPM i.v. infusion using PVC infusion bags and PVC administration sets.