How to Solve Drug Delivery Challenges of Cannabinoids Using Nanotechnology

Liposomes, nanoemulsions and polymeric nanoparticles have all shown promise in improving the therapeutic benefits of cannabinoids, but the full potential of these therapies has not yet been unlocked. Nanotechnology for active pharmaceutical ingredients (APIs), in this case cannabis compounds, is the use of carrier molecules to deliver the active.

Cannabinoids, as insoluble drugs, are currently targeted to over 117 indications in 500+ clinical trials (clinicaltrials.gov). The vast majority of these trials are being conducted with drug delivery formulations that involve oils or are dried flower for smoking. There is also a growing list of discovered cannabinoids (140+) emerging as drug candidates or as combination APIs with other formulations. The expanding benefits of cannabinoids all require increased bioavailability, tuned release and improved stability to become efficacious therapies.

These challenges can be addressed using nanoparticles. The research remains to be done however, on what excipients and particle characteristics are best suited to any given therapeutic purpose (ailment, administration route, pharmacodynamics, pharmacokinetics). What is clear in the literature is the effectiveness of nanoemulsions to approaching the bioavailability of inhaled cannabis through oral administration. Reviews of different administrations report inhalation as the most efficient route boasting upwards of 56% absorption of cannabinoids where oral ingestion of carrier oil formulations does not exceed 10% in most cases (Huestis, 2007; McGilveray, 2005; Ohlsson, 1980).

Considering cannabinoids are taken through a first pass metabolism in the liver, nanoparticles are a natural solution to bypass that effect due to size exclusion criteria in the small intestine or in buccal absorption in the mouth. Polysorbates have long been used to emulsify oils in food and beverage applications, and they have been successful in recreational cannabis applications for CBD and THC extracts. These nanoemulsions are just the tip of the iceberg and a number of groups are researching more sophisticated excipient systems for cannabinoid delivery, such as Ascension Sciences’ liposomal, solid lipid and polymer-based particles (Figure 1).

Figure 1. A variety of THC loaded nanoparticles.

Cannabinoids can be entrapped into different nanoparticle systems to solve specific drug delivery challenges; namely, increasing bioavailability, timing release, absorption via different administration routes and tuning pharmacodynamics.

Novel products and therapies in cannabis are being created using systems borrowed from the food and beverages industries, and carried over from other insoluble drug delivery methods. The instrumentation for top-down particle formulation is particularly well suited to nanoemulsions, namely sonication and high-pressure homogenization. These methods are scalable, but do have challenges such as the creation of heat (which can degrade cannabinoids), low repeatability, slow throughput for small screening and leading generation studies.

At the bench scale, using a bottom-up approach to assemble cannabinoid nanoparticles via low-energy microfluidics provides a repeatable and controllable process to study many different excipient systems in this space (Figure 2).

Nanoprecipitation via controlled solvent displacement in a microfluidic mixer for nanoparticle formulation.

1) Organic (ethanol) phase containing excipients and cannabinoids and aqueous (PBS) phase enter the mixing channel under laminar flow.

2) Microscopic features in the channel cause fluid streams to mix in a controlled fashion.

3) Fluids emerge completely mixed in milliseconds eliminating mixing gradients and causing the particles to form in a uniform and controlled manner.

The power of the microfluidic mixing lies in its flexibility, repeatability and speed. The approach lends itself well to a variety of particle formats (liposomes, nanoemulsions, polymer nanoparticles), and in screening experiments where multiple variables and design of experiment are important (Figure 3).

Figure 3. Studying the effects of different lipids on size and PDI for THC loaded liposomes.The microfluidic approach to mixing nanoparticles is particularly powerful in screening formulation lipids and other variables.

Ascension Sciences’ R&D and formulation development services are an efficient option for research driven firms that require the advantages of nanoparticle delivery for their cannabinoid actives. Small volume screening techniques allow ASI to test more nanoparticle compositions, more efficiently. ASI’s formulation technology and testing services span all areas of nanoparticle development (shelf-life stability testing, encapsulation efficiency, and dissolution profiles).

About Ascension Sciences
Employing nanoparticle formulation technology from the cutting edge of genetic medicine, Ascension Sciences Inc. (ASI) is developing cannabinoid nano delivery platforms and techniques for the pharma and nutraceutical industries. Our library of proprietary formulations and compounds can help solve any number of drug delivery challenges. Based in Vancouver, BC, Canada, ASI is an independent and licensed lab under Health Canada for cannabinoid nanoparticle R&D. We work with other passionate researchers in the industry that share a common goal of improving the human condition and bringing novel therapies to those who need them most.

Stay connected on LinkedIn and Twitter. For more information, please visit www.ascensionsciences.com.

References
Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007 Aug;4(8):1770-804. doi: 10.1002/cbdv.200790152. PMID: 17712819; PMCID: PMC2689518.

McGilveray IJ. Pharmacokinetics of cannabinoids. Pain Res Manag. 2005 Autumn;10 Suppl A:15A-22A. doi: 10.1155/2005/242516. PMID: 16237477.

Ohlsson A, Lindgren JE, Wahlen A, Agurell S, Hollister LE, Gillespie HK. Plasma delta-9 tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin Pharmacol Ther. 1980 Sep;28(3):409-16. doi: 10.1038/clpt.1980.181. PMID: 6250760.

excipients formulation