The effect of Pro NanoLipospheres (PNL) formulation containing natural absorption enhancers on the oral bioavailability of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a rat model

Cherniakov, Irina; Izgelov, Dvora; Domb, Abraham J.

doi:10.1016/j.ejps.2017.07.003

Cited by 88 publications

(57 citation statements)

References 28 publications

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“…Oral capsules with piperine pro-nanolipospheres also increased AUC and C max . This is also demonstrated in animal studies; co-administration of lipids with oral CBD increased systemic availability by almost 3-fold in rats (Zgair et al, 2016 ) and a pro-nanoliposphere formulation increased oral bioavailability by about 6-fold (Cherniakov et al, 2017b ). As CBD is a highly lipophilic molecule, it is logical that CBD may dissolve in the fat content of food, increasing its solubility, and absorption and therefore bioavailability as demonstrated by numerous pharmacological drugs (Winter et al, 2013 ).…”

Section: Discussionmentioning

confidence: 82%

A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans

Millar

Stone

Yates³

et al. 2018

Front. Pharmacol.

395

353

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Background: Cannabidiol is being pursued as a therapeutic treatment for multiple conditions, usually by oral delivery. Animal studies suggest oral bioavailability is low, but literature in humans is not sufficient. The aim of this review was to collate published data in this area.Methods: A systematic search of PubMed and EMBASE (including MEDLINE) was conducted to retrieve all articles reporting pharmacokinetic data of CBD in humans.Results: Of 792 articles retireved, 24 included pharmacokinetic parameters in humans. The half-life of cannabidiol was reported between 1.4 and 10.9 h after oromucosal spray, 2–5 days after chronic oral administration, 24 h after i.v., and 31 h after smoking. Bioavailability following smoking was 31% however no other studies attempted to report the absolute bioavailability of CBD following other routes in humans, despite i.v formulations being available. The area-under-the-curve and Cmax increase in dose-dependent manners and are reached quicker following smoking/inhalation compared to oral/oromucosal routes. Cmax is increased during fed states and in lipid formulations. Tmax is reached between 0 and 4 h.Conclusions: This review highlights the paucity in data and some discrepancy in the pharmacokinetics of cannabidiol, despite its widespread use in humans. Analysis and understanding of properties such as bioavailability and half-life is critical to future therapeutic success, and robust data from a variety of formulations is required.

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Section: Discussionmentioning

confidence: 82%

A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans

Millar

Stone

Yates³

et al. 2018

Front. Pharmacol.

395

353

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“…PTL401 is the proprietary PNL-based formulation of THC and CBD. The PTL401 formulation is composed of THC-CBD (1:1) in a formulation with polysorbate 20, sorbitan monooleate 80, polyoxyethylene hydrogenated castor oil 40, glyceryl tridecanoate, lecithin and ethyl lactate [ 129 , 130 ]. The CBD-THC PNL formulation also allows absorption enhancers, such as curcumin, resveratrol and piperine, to be incorporated.…”

Section: Current Drug Dosage Forms and Novel Delivery Systemsmentioning

confidence: 99%

“…The CBD-THC PNL formulation also allows absorption enhancers, such as curcumin, resveratrol and piperine, to be incorporated. PK evaluations in a rat model have indicated that only piperine enhanced the oral bioavailability of CBD in-vivo [ 130 ]. Moreover, the enhanced oral bioavailability can be attributed to the inhibition of intestinal processes, rather than those of hepatic first-pass metabolism, while additional increases in the AUC of CBD prove that piperine-PNL also has an effect on phase II, and not on just phase I, metabolism.…”

Section: Current Drug Dosage Forms and Novel Delivery Systemsmentioning

confidence: 99%

Cannabinoid Delivery Systems for Pain and Inflammation Treatment

Bruni¹,

et al. 2018

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There is a growing body of evidence to suggest that cannabinoids are beneficial for a range of clinical conditions, including pain, inflammation, epilepsy, sleep disorders, the symptoms of multiple sclerosis, anorexia, schizophrenia and other conditions. The transformation of cannabinoids from herbal preparations into highly regulated prescription drugs is therefore progressing rapidly. The development of such drugs requires well-controlled clinical trials to be carried out in order to objectively establish therapeutic efficacy, dose ranges and safety. The low oral bioavailability of cannabinoids has led to feasible methods of administration, such as the transdermal route, intranasal administration and transmucosal adsorption, being proposed. The highly lipophilic nature of cannabinoids means that they are seen as suitable candidates for advanced nanosized drug delivery systems, which can be applied via a range of routes. Nanotechnology-based drug delivery strategies have flourished in several therapeutic fields in recent years and numerous drugs have reached the market. This review explores the most recent developments, from preclinical to advanced clinical trials, in the cannabinoid delivery field, and focuses particularly on pain and inflammation treatment. Likely future directions are also considered and reported.

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“…Available data show that oral administration of CBD-piperine-PNL leads to a 6-fold increase in AUC when compared to a free CBD solution. Pharmacokinetic experiments of THC-piperine-PNL showed a similar behaviour with a 9.3-fold increase in the AUC when compared to the free THC solution [113].…”

Section: Advanced Pro-nanoliposphere (Pnl)mentioning

confidence: 63%

Challenges and Opportunities in Preclinical Research of Synthetic Cannabinoids for Pain Therapy

et al. 2020

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Cannabis has been used in pain management since 2900 BC. In the 20th century, synthetic cannabinoids began to emerge, thus opening the way for improved efficacy. The search for new forms of synthetic cannabinoids continues and, as such, the aim of this review is to provide a comprehensive tool for the research and development of this promising class of drugs. Methods for the in vitro assessment of cytotoxic, mutagenic or developmental effects are presented, followed by the main in vivo pain models used in cannabis research and the results yielded by different types of administration (systemic versus intrathecal versus inhalation). Animal models designed for assessing side-effects and long-term uses are also discussed. In the second part of this review, pharmacokinetic and pharmacodynamic studies of synthetic cannabinoid biodistribution, together with liquid chromatography–mass spectrometric identification of synthetic cannabinoids in biological fluids from rodents to humans are presented. Last, but not least, different strategies for improving the solubility and physicochemical stability of synthetic cannabinoids and their potential impact on pain management are discussed. In conclusion, synthetic cannabinoids are one of the most promising classes of drugs in pain medicine, and preclinical research should focus on identifying new and improved alternatives for a better clinical and preclinical outcome.

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The effect of Pro NanoLipospheres (PNL) formulation containing natural absorption enhancers on the oral bioavailability of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a rat model

Cited by 88 publications

References 28 publications

A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans

A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans

Cannabinoid Delivery Systems for Pain and Inflammation Treatment

Challenges and Opportunities in Preclinical Research of Synthetic Cannabinoids for Pain Therapy

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