ProNano-Liposphers (PNL) for Oral Delivery of Cannabis

Abraham J. Domb, Institute of Drug Research, School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
Dvora Izgelov, Institute of Drug Research, School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
Eliyahu Shmoeli, Institute of Drug Research, School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
Amnon Hoffman, Institute of Drug Research, School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel

Cannabis agents such as CBD and THC are water insoluble and sensitive to metabolism after oral intake. The oral bioavailability of cannabis agents is in the range of 5-8%. To increase the bioavailability of CBD and THC, they have been formulation in PNL formulations which significantly improved their bioavailability.

Many dispersion systems are currently in use as carriers of insoluble drugs. Pro-NanoLiposphere (PNL), is based on a solution of the drug in a mixture of triglyceride, phospholipid, surfactants, and a water miscible organic solvent. This solution spontaneously forms nanoparticles (<50 nm) when gently mixed in an aqueous media, such as the upper GI lumen content. When given orally, a drug is absorbed into the enterocytes monolayer in the basolateral side of the intestine. From the apical side of the enterocytes the drug is delivered via the portal vein to the liver and thereafter into the systemic blood circulation. Bioavailability is one of the essential tools in pharmacokinetics, as it must be considered when calculating dosages for none intravenous routes of administration.

PNL oral formulation for cyclosporine has been developed for clinical use. Similar formulations were developed for CBD and THC that has been tested in rats and humans for oral bioavailability. CBD and THC blood levels in humans after intake of 10mg single dose were determined using LCMS. These formulations are in clinical development for treating disorders affected by cannabinoid agents.

Reference
1- Cherniakov I, AJ Domb, A Hoffman, Self-nano-emulsifying drug delivery systems: an update of the biopharmaceutical aspects, Expert opinion on drug delivery, (2014), 12(7): 1121-1133