Potential Benefit of Zygel:
Zygel is a unique permeation-enhanced CBD transdermal gel. Transdermal therapeutics are applied locally and absorbed through the skin directly into the systemic circulation, resulting in a lower incidence of gastrointestinal side effects, and avoidance of first-pass liver metabolism, which potentially enables lower dosage levels of active pharmaceutical ingredients and rapid, reliable absorption with increased bioavailability. Other potential benefits of transdermal delivery compared with oral administration may include fewer drug-drug interactions.
CBD and other cannabinoids are large, complex molecules that do not penetrate the skin efficiently without the use of technologies that improve their penetration. As such, topical formulations of CBD or oils derived from Cannabis may require very high doses to reach therapeutic blood levels, or may not cross the skin and into the bloodstream at all.
Addressing Limitations of Current Treatments
Potential Benefit of Zygel:
Zygel is a proprietary pharmaceutically-manufactured CBD gel formulated with permeation enhancers, which improve the ability of CBD to cross through the skin and into the bloodstream when administered directly to the skin (transdermal delivery).
Zygel is a pharmaceutically-produced CBD formulated as a permeation-enhanced gel for transdermal delivery.
Challenge: Oral administration
36. Bickers DR, Athar M. Oxidative stress in the pathogenesis of skin disease. J Invest Dermatol. 2006;126(12):2565–2575.
159. Shen J-L, Man K-M, Huang P-H, et al. Honokiol and magnolol as multifunctional antioxidative molecules for dermatologic disorders. Molecules. 2010;15(9):6452–6465. doi:10.3390/molecules15096452
Potential of Cannabidiol for Skin Health and Dermatological Conditions
Atopic Dermatitis (AD) is a chronic inflammatory skin disorder associated with multifactorial causes like environmental triggers, damaged skin barrier function, microbiome imbalance, genetic predisposition, and an altered immune response. 57 Phytocannabinoids have been shown to modulate inflammatory responses by regulating more than one underlying mechanism. Adelmidrol, a PEA derivative, has been shown to be effective in treating mild AD in a pediatric population. 58 Though the efficacy of CBD is yet to be clinically validated, in a recent study by Petrosino et al, CBD was shown to exhibit anti-inflammatory properties in an experimental, allergic contact dermatitis model. 59
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95. Ramot Y, Oláh A. Cover Image: neuroendocrine treatment of inherited keratin disorders by cannabinoids? British J Dermatol. 2018;178(6):1469.
A CBD therapeutic formulation is being developed by Kalytera Therapeutics for the prevention and treatment of graft-versus-host disease. Kalytera initiated a randomised, open-label, dose-response and comparator-controlled phase IIb trial in December 2017 to evaluate the pharmacokinetic profile, safety and efficacy of multiple doses of CBD for the prevention of graft-versus-host-disease following allergenic haematopoietic cell transplantation ( <"type":"clinical-trial","attrs":<"text":"NCT02478424","term_id":"NCT02478424">> NCT02478424).
A system, which combines method, devices and systems, for the controlled pulmonary delivery of active agents has also been reported; a metered dose inhaler to vaporize precise amount of agent (cannabinoids or other plant oils), a system for the evaluation of the PK value obtained after one or two puffs and an interface for the control of the profile of the drug administered have been provided by Davidson et al. .
3.2. Administration through Mucosa
Beyond its effects on the inflammatory pathway, the endocannabinoid system also plays a fundamental role in neuronal development affecting axon and dendrite growth  and preclinical models have demonstrated that cannabinoid administration alters brain maturation in young animals and leads to neuropsychiatric consequences in adults . Moreover, endocannabinoid system has also been accepted to play a significant role in the maintenance of gut homeostasis, and this is therefore, of particular interest in the management of inflammatory bowel diseases (i.e., Crohn’s disease and ulcerative colitis) that show increasing prevalence in Westernised countries .
Several patents have presented systems for vaporisation and nebulisation, from a variety of containers , at a selected temperature to form a precise amount of vapour with THC and CBD . Improved drug-delivery devices that can separate and release active cannabis substances have been disclosed in another patent ; drug delivery cartridges, which include a substrate coated with at least one of either THC or CBD, are configured to allow for the passage of air through the cartridge to volatilise the agent for inhalation by a user.
The chronic pathological pain state, including neuropathic pain, is a leading health problem worldwide as it endures beyond the resolution of the pain source and can deeply impact quality of life . Unlike physiological pain, in which tissue injury and/or inflammation can induce reversible adaptive changes in the sensory nervous system leading to protective sensitization, changes in sensitivity become persistent or chronic in neuropathic pain. Furthermore, the nervous system, peripheral or central, is injured in neuropathic pain. It is characterised by pain in the absence of a noxious stimulus and may be spontaneous in its temporal characteristics or be evoked by sensory stimuli (hyperalgesia and dynamic mechanical allodynia). For example, neuropathy is still among the most common diabetes complications, affecting up to 50% of patients, despite recent advances in treatment. There is no effective treatment with which to prevent or reverse neuropathic pain , thus current treatment is only directed at reducing symptoms. The treatment of chronic pain is still an unmet clinical need, where adequate pain relief is obtained using drugs with adverse effects on central nervous system side . The quality of life of neuropathic pain patients is often aggravated by comorbidities such as sleep disorders, depression and anxiety compromise.