Delivery of THC derivatives across the BBB: functionalised polysaccharides nanocarriers

Cannabis sativa, commonly known as marijuana has been found to contain 525 natural components that fall under several chemical classes. Cannabinoids fit in the chemical class of terpenophenolics and 104 of them have been identified so far (El-Alfy et al., 2010, Lafaye et al., 2017). Δ9-tetrahydrocannabinol (THC) is the most active component of the plant due to its high potential and profusion in plant preparations (Velasco et al., 2012). Studies have shown that THC mimics the endogenous substances, anandamide and 2-AG, by binding to the CB receptors inducing different pathways, eventually leading to the reduction of tumour growth (Pertwee, 2008).

Other distinguished cannabinoids also exist such as cannabidiol (CBD), cannabinol (CBN) and cannabigerol (CBG) that exert anticancer activity of which an important feature of CBD and CBG is the lack of psychoactive effects , (Scott et al., 2014). The non-psychoactive cannabinoids have minor attraction for the CB receptors hence they do not elicit their activity through these receptors. Instead, CBD induces apoptosis by the possible mechanism of induction of oxidative stress through the accumulation of reactive oxygen species (ROS) (Massi et al., 2006).

In 1981, a synthetic analogue of Δ9-THC was licensed for the inhibition of vomiting and nausea-induced from chemotherapy and in 1992 it was used as an appetite stimulant (Pertwee, 2009). In 2005, one more cannabis-based medicine, Sativex, entered the clinic containing similar amounts of Δ9-THC and CBD and is used by adult patients with advanced cancer as a complementary analgesic treatment (Pertwee, 2009).

The function of the endocannabinoid system in tumour generation and development has gained a lot of interest in the last decade. Malfitano et al. (2011) showed that overexpression of endocannabinoids and their receptors is correlated with cancer and tumour aggressiveness. Cannabinoids have been explored for the treatment of variety of conditions such as, fear and anxiety (Murkar et al., 2021), cancer (Kyriakou et al., 2021), dermatologic conditions (Sivesind et al., 2022), and respiratory diseases (Kicman et al., 2021).

Our group has extensively studied functionalised polysaccharides nanocarriers as a means of overcoming the blood-brain barrier. As part of our extended studies, we will also consider some of the polymers suitable to form films which might prove useful in delivering the active ingredients considered in this study.

This study aims to develop nanoparticles of in-house modified polysaccharides with CBD and THC, to achieve a high loading capacity and targeted anti-cancer drug delivery. In vitro testing will also be utilised for determining the passage of nanoparticles through the BBB and their functionality.