Conjugation to PEG as a Strategy to Limit the Uptake of Drugs by the Placenta: Potential Applications for Drug Administration in Pregnancy

Mol Pharm. 2022 Jan 3;19(1):345-353. doi: 10.1021/acs.molpharmaceut.1c00498. Epub 2021 Nov 29.

Abstract

Here, we evaluated the feasibility of non-prodrug PEG-drug conjugates to decrease the accumulation of drugs within the placental tissues. The results showed that PEG was biocompatible with the human placenta with no alteration of the basal rate of proliferation or apoptosis in term placental explants. No significant changes in the released levels of lactate dehydrogenase and the human chorionic gonadotropin were observed after PEG treatment. The cellular uptake studies revealed that conjugating Cy5.5 and haloperidol to PEG significantly reduced (by up to ∼40-fold) their uptake by the placenta. These findings highlight the viability of novel non-prodrug polymer-drug conjugates to avoid the accumulation of drugs within the placenta.

Keywords: PEG; drug delivery; placenta; polymer−drug conjugate; pregnancy; transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Compounding / methods
  • Female
  • Haloperidol / pharmacokinetics
  • Humans
  • Placenta / drug effects
  • Placenta / metabolism*
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / chemistry*
  • Polymers
  • Pregnancy
  • Pregnancy Complications / drug therapy*

Substances

  • Polymers
  • Polyethylene Glycols
  • Haloperidol