Cannabidiol formulation development: in vitro and ex vivo investigation of cannabidiol containing transfersomal formulations for the management of haemorrhoids

Abstract

Cannabidiol is a non-psychoactive compound of cannabis that has been demonstrated to alleviate pain and inflammation. However, its clinical application is hampered by disadvantages such as limited oral bioavailability, photo- and heat instability, and uneven release and absorption. Adapting nanotechnology into rectal delivery system can counteract drawbacks of cannabidiol (CBD). In this study, the transfersomes colloid were developed to enhance CBD bioavailability, absorption, and stability as a rectal colloid, that can be used to manage haemorrhoidal pain and inflammation. Thin film evaporation was used to produce transfersomes containing variable amount of polysorbate 80, cholesterol (30mg) and soya lecithin (60 mg), which were then tested for size, entrapment capacity%, shape, release profile, ex vivo permeability, and stability. The advanced transfersomes colloid was incorporated into ratios of 95% P407:5%PEG1000 and 75% PEG1000:25% PEG6000 bases to form suppositories using fusion mould method. Drug release study, hardness, mass difference, content homogeneity, disintegration time, cytotoxicity, and in vitro anti-inflammatory study were performed on suppositories. The advanced transfersome colloids had a particle size of 130.1 nm ± 0.64, polydispersity index of 0.285 ± 0.0056, and surface charge of -15.97 mV ± 1.30, the advanced formulation for rectal distribution entrapped up to 80.0% ± 0.077 of CBD. The morphological study of transfersomes using scanning electron microscope (SEM) and transmission electron microscope (TEM) revealed their spherical shape and nanoscale, which attributed to improved ex vivo permeability of CBD-transfersomes colloid across the excised rat colonic membrane compared to free CBD. The CBD-loaded transfersomes suppositories controlled the release of CBD, with 95% CBD released within the period of 6 hours. In vitro anti-inflammatory studies proved the anti-inflammatory properties of CBD, CBD inhibited protein modification at all concentrations, with the highest inhibition of 96.4% at 75 mg/mL. The anti-inflammatory properties of CBD were comparable with the well-known potent antiinflammatory drug diclofenac. Additionally, transfersomes increased the stability of the entrapped CBD for up to half a year at ambient environmental conditions. CBD-transfersomes colloid reduced CBD toxicity on caco2 cells by around 70%. Because of the controlled release profile of CBD, CBD-loaded transfersomes colloid suppositories have the potential to relieve pain for an extended period. Moreover, enhanced stability of CBD under ambient environmental conditions implies that CBD-transfersomes colloid improve CBD shelf life. Overall, this study demonstrated the effectiveness of CBD to manage inflammation and pain associated with haemorrhoids, furthermore this formulation can be useful to patients under palliate care.