title: Investigation of the release behavior of DEHP from infusion sets by paclitaxel-loaded polymeric micelles.
abstract: 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 3h 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.
authors.affiliation: Samyang Research Co., 9520 South State Street, Sandy, UT 84070, USA. schulkim@yahoo.com
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Kim
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Jang Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Jaewon
authors.initials: J
authors.lastname: Yu
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Park
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Chi
mesh_terms: D004051:Diethylhexyl Phthalate / Q000737:chemistry / Q000493:pharmacokinetics*; D007260:Infusion Pumps; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D008823:Micelles; D011108:Polymers; D004051:Diethylhexyl Phthalate; D017239:Paclitaxel