2.5D printing of sustained-release polymeric microdepots for whole plant medical cannabis delivery

Recent decades have seen a major increase in the use of medical Cannabis as its therapeutic value became better recognized and accepted. Administration of whole-plant extracts rather than isolated molecules harnesses the synergistic effects between the numerous active compounds. While the prescription of medical Cannabis for various indications constantly grows, its consumption is mostly limited to oral or respiratory pathways, impeding its duration of action, bioavailability and efficacy.

In this work, we describe a novel approach using long-acting polymeric microspheres prepared via melt-printing technique (2.5D printing), performing as depots, for the administration of the full plant spectrum. When injected subcutaneously in mice, the microdepots facilitated the sustained release of the encapsulated extract over a two-week period. This prolonged delivery results in elevated serum levels of multiple phytocannabinoids, both major and minor, for over two weeks, compared to a bolus injection of Cannabis extract. Thus, demonstrating the potential of the formulation in improving the systemic exposure and increasing the effectiveness of the therapy. Direct analysis of microdepots retrieved from the injection site gave rise to an empirical model for the release kinetics of the phytocannabinoids as a function of their physical traits.

In a preliminary study, we evaluated the long-term therapeutic potential of a single administration of the microdepots compared to a single administration of Cannabis extract in pentylenetetrazol-induced convulsions epilepsy model. One week following administration, the microdepots reduced the incidence of tonic-clonic seizures by 40% and increased the survival rate by 50% and the latency to first tonic-clonic seizures by 170%. These results suggest that a long-term full-spectrum Cannabis delivery system may provide a novel path for more effective Cannabis administration and treatments.