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

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

Successive tendon injury in an in vivo rat overload model induces early damage and acute healing responses

Introduction: Tendinopathy is a degenerative condition resulting from tendons experiencing abnormal levels of multi-scale damage over time, impairing their ability to repair. However, the damage markers associated with the initiation of tendinopathy are poorly understood, as the disease is largely characterized by end-stage clinical phenotypes. Thus, this study aimed to evaluate the acute tendon responses to successive fatigue bouts of tendon overload using an in vivo passive ankle dorsiflexion system.Methods: Sprague Dawley female rats underwent fatigue overloading to their Achilles tendons for 1, 2, or 3 loading bouts, with two days of rest in between each bout. Mechanical, structural, and biological assays were performed on tendon samples to evaluate the innate acute healing response to overload injuries.Results: Here, we show that fatigue overloading significantly reduces in vivo functional and mechanical properties, with reductions in hysteresis, peak stress, and loading and unloading moduli. Multi-scale structural damage on cellular, fibril, and fiber levels demonstrated accumulated micro-damage that may have induced a reparative response to successive loading bouts. The acute healing response resulted in alterations in matrix turnover and early inflammatory upregulations associated with matrix remodeling and acute responses to injuries.Discussion: This work demonstrates accumulated damage and acute changes to the tendon healing response caused by successive bouts of in vivo fatigue overloads. These results provide the avenue for future investigations of long-term evaluations of tendon overload in the context of tendinopathy