Towards long-acting adrenaline for cardiopulmonary resuscitation: Production and characterization of a liposomal formulation

Int J Pharm. 2019 Feb 25:557:105-111. doi: 10.1016/j.ijpharm.2018.12.044. Epub 2018 Dec 23.

Abstract

The use of adrenaline in cardiopulmonary resuscitation is a long-standing medical procedure, recommended by several international guidelines. However, its unspecific action on adrenergic receptors and the need for repeated administrations pose serious concerns about its safety, the balance between benefits and risks being still under debate. To address this issue, a sustained release nano-formulation of adrenaline was developed. Adrenaline was encapsulated into PEGylated, anionic liposomes by a pH-driven loading technique. Particular attention was devoted to the prevention of oxidation of adrenaline by optimizing the preparative process and including an optimal amount of antioxidants in the formulation. The vesicles obtained were then characterized for size, zeta-potential, and lamellarity, while their morphology was described by cryo-TEM. The controlled release properties were confirmed by two different in vitro release-testing methods, and the biocompatibility was assayed on human endothelial cells in vitro.

Keywords: Cardiac arrest; Epinephrine; Phospholipid vesicles; Remote loading; pH-driven loading.

MeSH terms

  • Antioxidants / administration & dosage
  • Antioxidants / chemistry
  • Cardiopulmonary Resuscitation
  • Cells, Cultured
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemistry
  • Drug Liberation
  • Epinephrine / administration & dosage*
  • Epinephrine / chemistry
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Hydrogen-Ion Concentration
  • Liposomes
  • Sulfites / administration & dosage
  • Sulfites / chemistry

Substances

  • Antioxidants
  • Delayed-Action Preparations
  • Liposomes
  • Sulfites
  • sodium metabisulfite
  • Epinephrine