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

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
• clonazepam
• cellular uptake
• cytotoxicity
• transplacental transport

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by the Turkish Scientific and Technological Research Council (TÜBİTAK grant number 112S529). YME acknowledges the support of the Turkish Academy of Sciences, Ankara, Turkey, as associate member.