β-caryophyllene Delivery Systems: Enhancing the Oral Pharmacokinetic and Stability

The β-caryophyllene (BCP), a phytocannabinoid present in various essential oils, demonstrated selective action on the CB2 endocannabinoid receptor and attracted considerable attention because of its several pharmacological activities. Despite this recognized potential, this hydrophobic compound is a volatile and acid-sensitive sesquiterpene that readily oxidizes when exposed to air, and has low bioavailability in oral formulations. Thus, the development of formulations that guarantee its stability and increase its bioavailability is a challenge for its use in the pharmaceutical field.

The present review brings for the first time a comprehensive overview of the controlled and vectorized release formulations tested for BCP administration. Among these, we have addressed nanoemulsions, inclusion complexes with cyclodextrins, liposomes, wound dressings, nanocomposites and nanoparticles. A literature search was performed on Pubmed, Web of Science and Science direct, and patents documents were also searched on European Patent Office, World Intellectual Property Organization and Brazilian National Institute of Industrial Property.

The systems presented here may represent an interesting approach to overcome the limitations already mentioned for this terpene. These systems proved to be promising for improving solubility, stability and controlled release of this pharmacological relevant sesquiterpene. In the industrial field, some companies have filed patent applications for the commercial use of the BCP, however, the use of pharmaceutical formulations still appeared moderate.

This prospective study evidenced the new perspectives related to BCP vectorization systems in the pharmaceutical and industrial marketing field and may serve as a basis for further research and pharmaceutical use of this powerful cannabinoid.