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 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.
Kim
Sung Chul
SC
Samyang Research Co., 9520 South State Street, Sandy, UT 84070, USA. schulkim@yahoo.com
Yoon
Hye Jeong
HJ
Lee
Jang Won
JW
Yu
Jaewon
J
Park
Eun-Seok
ES
Chi
Sang-Cheol
SC
D004051:Diethylhexyl Phthalate / Q000737:chemistry / Q000493:pharmacokinetics*; D007260:Infusion Pumps; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics*
D008823:Micelles; D011108:Polymers; D004051:Diethylhexyl Phthalate; D017239:Paclitaxel