Investigation of potential cardiovascular effects of the Pheroid® delivery system in conscious rats

Abstract

Aim: The aim of this study was to evaluate the possible cardiovascular effects of the Pheroid® drug delivery system and to determine the possible central nervous effects of its combination with cannabidiol (CBD) in the conscious rat. Introduction: This project utilizes the principles of safety pharmacology to evaluate the cardiovascular safety of the Pheroid® drug delivery system using a telemetry-based acquisition system and the central nervous safety of a Pheroid®-CBD combination using a standard open-field test. The Pheroid® is a colloidal drug delivery system comprised of a dispersed oil phase of omega 3 and omega 6 fatty acids emulsified in N2O saturated water. Pheroid® boasts a range of pharmaceutical applicability, among others for the enhancement of therapeutic efficacy due to better drug exposure, reduced cytotoxicity and faster onset of action. A demonstration of its lack of unwanted physiological effects could open the opportunity for further pharmaceutical applications. Methods: Eight male rats were instrumented with telemetry transmitters of which six were subsequently used to determine the safety of single intravenous (IV) and oral administration of the Pheroid® delivery system on cardiovascular parameters; including arterial blood pressure, heart rate and the ECG. The reference, positive control compounds were selected as follows: a single intraperitoneal dose of clonidine (0.03 mg/kg) and an oral dose of theophylline (30 mg/kg). For the assessment of the central nervous safety of a Pheroid®-CBD formulation, an open-field test was conducted on 18 male rats divided into three groups of six: CBD (10 mg/kg), pro-Pheroid®-CBD (10 mg/kg) and a control. Results: No significant effects of Pheroid® on cardiovascular parameters were observed at any time following oral or intravenous administration. The expected effects of clonidine and theophylline could be demonstrating confirming the sensitivity of the experimental model to detect changes in the cardiovascular parameters measured. No behavioural effects were reported after assessment of the Pheroid®-CBD formulation on central nervous function. Discussion: This project has demonstrated that Pheroid® and its combination with CBD have no effects on cardiovascular or central nervous function respectively. These data showing cardiovascular and central nervous safety are supportive for the use of Pheroid® for various pharmacological applications.