Propylene glycol and Kolliphor as solvents for systemic delivery of cannabinoids via intraperitoneal and subcutaneous routes in preclinical studies: a comparative technical note

Kaveh Momenzadeh; Diana Yeritsyan; Nadim Kheir; Rosalyn M Nazarian; Ara Nazarian

doi:10.1186/s42238-023-00194-9

Propylene glycol and Kolliphor as solvents for systemic delivery of cannabinoids via intraperitoneal and subcutaneous routes in preclinical studies: a comparative technical note

J Cannabis Res. 2023 Jun 20;5(1):24. doi: 10.1186/s42238-023-00194-9.

Authors

Kaveh Momenzadeh^#¹, Diana Yeritsyan^#¹, Nadim Kheir¹, Rosalyn M Nazarian², Ara Nazarian^{3

4}

Affiliations

¹ Musculoskeletal Translational Innovation Initiative, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA.
² Pathology Service, Dermatopathology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
³ Musculoskeletal Translational Innovation Initiative, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA. anazaria@bidmc.harvard.edu.
⁴ Department of Orthopaedic Surgery, Yerevan State Medical University, Yerevan, Armenia. anazaria@bidmc.harvard.edu.

^# Contributed equally.

Abstract

Background: Substance administration to laboratory animals necessitates careful consideration and planning in order to enhance agent distribution while reducing any harmful effects from the technique. There are numerous methods for administering cannabinoids; however, several parameters must be considered, including delivery frequency, volume of administration, vehicle, and the level of competence required for staff to use these routes properly. There is a scarcity of information about the appropriate delivery method for cannabinoids in animal research, particularly those that need the least amount of animal manipulation during the course of the investigation. This study aims to assess the feasibility and potential side effects of intraperitoneal and subcutaneous injection of CBD and THC using propylene glycol or Kolliphor in animal models. By evaluating the ease of use and histopathological side effects of these solvents, this study intends to help researchers better understand an accessible long-term delivery route of administration in animal experiments while minimizing the potential confounding effects of the delivery method on the animal.

Methods: Intraperitoneal and subcutaneous methods of systemic cannabis administration were tested in rat models. Subcutaneous delivery via needle injection and continuous osmotic pump release were evaluated using propylene glycol or Kolliphor solvents. In addition, the use of a needle injection and a propylene glycol solvent for intraperitoneal (IP) administration was investigated. Skin histopathological changes were evaluated following a trial of subcutaneous injections of cannabinoids utilizing propylene glycol solvent.

Discussion: Although IP delivery of cannabinoids with propylene glycol as solvent is a viable method and is preferable to oral treatment in order to reduce gastrointestinal tract degradation, it has substantial feasibility limitations. We conclude that subcutaneous delivery utilizing osmotic pumps with Kolliphor as a solvent provides viable and consistent route of administration for long-term systemic cannabinoid delivery in the preclinical context.

Keywords: Animal models; Cannabinoids; Drug delivery; Route of administration; Skin histopathology.