An oral nanoformulation of Δ9-THC for CINV, pain and cachexia in AIDS and cancer patients and Multiple Sclerosis.
Δ9-THC – The Active Pharmaceutical Ingredient of Marijuana
Tetrahydrocannabinol (Δ9-THC), the active pharmaceutical ingredient of marijuana (Cannabis sativa), is very hydrophobic and oxygen-sensitive. Both of these factors present challenges to making stable, orally bioavailable formulations.
In the currently marketed formulation, synthetic Δ9-THC (Dronabinol) is dissolved in sesame seed oil and is commercially available as an oral capsule (Marinol®). Dronabinol suffers from high incidence of adverse side effects and low bioavailability (only 6-20% reaches systemic circulation) due to poor solubility of the highly lipophilic Δ9-THC in aqueous solution and high first-pass metabolism in the liver.
A metabolite of orally dosed Dronabinol, 11-OH-Δ9-THC, generated during the digestive processes is three times more psychoactive than Δ9-THC itself, with no indication of added medical benefit. The onset of action is slow, with peak plasma concentrations attained 2 to 4 hours after dosing. The most common adverse events associated with Dronabinol involve the central nervous system, including anxiety, confusion, depersonalization, dizziness, euphoria, dysphoria, somnolence, and cognitive impairment.
Oral administration in its current formulation causes slow, variable Δ9-THC uptake. In addition, it also requires frequent drug administration.
APH-0802, a nanoformulation of Δ9-THC – nanoTHC™
nanoTHC™ is a nanoencapsulation of Δ9-THC in biodegradable polymer nanospheres that allows transport of Δ9-THC to the stomach, improves stability and enhances bioavailability [US Patent Pending]. Alternatively, nanoTHC™ could be utilized to deliver Δ9-THC from a subcutaneously implanted depot.
nanoTHC™ is manufactured using Aphios’ patented polymer nanospheres encapsulation technologies [US Patents].
Improved Bioavailability with nanoTHC™
Nanoencapsulation is being used to protect the Δ9-THC during the stomach passage; the residence time in the stomach will be short compared to Δ9-THC release rate from polymer nanospheres.
When nanoTHC™ polymer nanospheres reach the small intestine, they can be transported across the lining, which may be mediated by M cells in the lymphatic tissue.
Alternatively, the Δ9-THC can be mobilized from nanoparticles and rapidly transported to the systemic circulation by the epithelial cells. The polymer “shell” is intended to enable and regulate this stage of drug transport while protecting the drug from first-pass metabolism in the liver. With the optimal biodegradable polymer nanospheres shell properties, we anticipate a significant improvement in oral bioavailability of Δ9-THC.
The biopharmaceutical rationale for utilizing biodegradable polymer nanospheres in sustained release drug delivery has been validated by several FDA approved drugs by companies such as Alkermes and Johnson & Johnson.
Potential Applications of nanoTHC™ – APH-0802
nanoTHC™ will improve therapeutic effectiveness of Δ9-THC for chemotherapy-induced nausea and vomiting, marijuana addiction, pain in cancer and AIDS patients, cachexia in cancer and HIV/AIDS patients as well as multiple sclerosis and several developing indications.