Investigations on clonazepam-loaded polymeric micelle-like nanoparticles for safe drug administration during pregnancy

J Microencapsul. 2018 Mar;35(2):149-164. doi: 10.1080/02652048.2018.1447615. Epub 2018 Mar 20.

Abstract

Medication during pregnancy is often a necessity for women to treat their acute or chronic diseases. The goal of this study is to evaluate the potential of micelle-like nanoparticles (MNP) for providing safe drug usage in pregnancy and protect both foetus and mother from medication side effects. Clonazepam-loaded MNP were prepared from copolymers [polystyrene-poly(acrylic acid) (PS-PAA), poly(ethylene glycol)-b-poly(lactic acid) (PEG-PLA) and distearyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-poly(ethylene glycol) (PEG-DSPE)] with varying monomer ratios and their drug-loading efficiency, drug release ratio, particle size, surface charge and morphology were characterised. The cellular transport and cytotoxicity experiments were conducted on clonazepam and MNP formulations using placenta-choriocarcinoma-BeWo and brain-endothelial-bEnd3 cells. Clonazepam-loaded PEG5000-PLA4500 MNP reduced the drug transport through BeWo cells demonstrating that MNP may lower foetal drug exposure, thus reduce the drug side effects. However, lipofectamine modified MNP improved the transport of clonazepam and found to be promising for brain and in-utero-specific drug treatment.

Keywords: Micelle-like nanoparticles; cellular uptake; clonazepam; cytotoxicity; transplacental transport.

MeSH terms

  • Acrylic Resins / adverse effects
  • Acrylic Resins / chemistry
  • Cell Line
  • Clonazepam / administration & dosage*
  • Clonazepam / adverse effects
  • Clonazepam / pharmacokinetics
  • Drug Carriers / adverse effects
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Female
  • GABA Modulators / administration & dosage*
  • GABA Modulators / adverse effects
  • GABA Modulators / pharmacokinetics
  • Humans
  • Lactates / adverse effects
  • Lactates / chemistry
  • Nanoparticles / adverse effects
  • Nanoparticles / chemistry*
  • Phosphatidylethanolamines / adverse effects
  • Phosphatidylethanolamines / chemistry
  • Placenta / drug effects
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / chemistry
  • Polymers / adverse effects
  • Polymers / chemistry*
  • Polystyrenes / adverse effects
  • Polystyrenes / chemistry
  • Pregnancy

Substances

  • Acrylic Resins
  • Drug Carriers
  • GABA Modulators
  • Lactates
  • Phosphatidylethanolamines
  • Polymers
  • Polystyrenes
  • poly(lactic acid-ethylene glycol)
  • polyethylene glycol-distearoylphosphatidylethanolamine
  • Polyethylene Glycols
  • carbopol 940
  • Clonazepam