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Adrenaline-containing double layered lipid vesicles for use in the treatment of cardiac emergencies

Prof. Sergio Murgia, University of Cagliari; Prof. Chiara Sinico, University of Cagliari; Dr Michele Schlich, University of Cagliari; Prof. Theodoros Xanthos, University of Cagliari; Dr Valeria Meli, University of Cagliari; Prof. Maura Monduzzi, University of Cagliari; Prof. Ernesto D’Aloja, University of Cagliari; Dr Emanuela Locci , University of Cagliari

University of Cagliari


The use of adrenaline in treatment of cardiopulmonary resuscitation is fundamental since it is capable of stimulating myocardial contraction and resumption of the heartbeat. However, especially in case of multiple injections (as prescribed by guidelines for cardiopulmonary resuscitation), its non-selective action exacerbates the ischaemia after the return of spontaneous circulation and increases the risk of neurological damage.


This invention consists in phospholipid-based liposomes loaded with adrenaline by a pH driven remote loading and shielded by polyethylene glycols from interactions with plasma proteins for a prolonged circulation in blood. Such a formulation is engineered to be used as an injectable colloidal dispersion for parenteral administration during cardiac emergencies. This formulation enables:

  1. Reduced number of injections in cardiopulmonary resuscitation;
  2. Improved adrenalin stability in blood circulation;
  3. Adrenalin sustained release after intravenous injection;
  4. Increased adrenalin half-life and duration of action;
  5. Reduced neurological risks associated to frequently repeated adrenalin administrations.

Commercial Opportunity

The injectable liposomal adrenaline formulation here proposed could be authorized by European (EMA) and/or American (FDA) regulatory agencies as a substitute of the adrenaline solution currently on the market in all the clinical applications where cardiopulmonary resuscitation is required. Examples concern cardiac emergencies of various types, such as cardiac arrest, ventricular fibrillation, pulseless ventricular tachycardia, pulseless cardiac electric activity, cardiac asystole. According to “Cardiopulmonary Resuscitation Market Research Report- Global Forecast To 2023 ID: MRFR/MED/0840-HCRR | January, 2019” the market for the Global Cardiopulmonary Resuscitation is dominated by the American region as more of the incidences of cardiac arrest are seen in the American countries. The second largest market is represented by Europe, where the number of cases are increasing. The Asia-Pacific region is also witnessing a continuous growth of cardiac patients, the young population being here more affected than in other regions. The market will grow steady at a rate of 7% CAGR during the forecasted period 2017-2023.

Development Status

The pharmaceutical composition has been developed and completely characterized in vitro in terms of physico-chemical and pharmaceutical properties. Preliminary in vivo pharmacokinetic data on pigs as animal model confirmed the sustained release effect of liposomal adrenaline compared to marketed adrenaline solutions. Preclinical efficacy studies on porcine models of cardiac arrest are planned.

Patent Situation

An International patent application has been filed recently. Worldwide patent protection is possible.

Further Reading

1. Schlich M, Sinico C, Valenti D, Gulati A, Joshi MD, Meli V, Murgia S, Xanthos T. Towards long-acting adrenaline for cardiopulmonary resuscitation: Production and characterization of a liposomal formulation. Int J Pharm. 2018 Dec 23;557:105-111. doi: 10.1016/j.ijpharm.2018.12.044.

2. Xanthos, T., Pantazopoulos, I., Demestiha, T., Stroumpoulis, K., 2011. Epinephrine in Ventricular Fibrillation: Friend or foe? A Review for the Emergency Nurse. J. Emerg. Nurs. 37, 408–412.

3. Ristagno, G., Tang, W., Huang, L., Fymat, A., Chang, Y., 2009. Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation. Crit. Care Med. 37.


Adrenaline-containing double layered lipid vesicles for use in the treatment of cardiac emergencies