Current trends on cannabidiol delivery systems: where are we and where are we going?

INTRODUCTION: Cannabidiol (CBD), a phytocannabinoid from Cannabis sativa, has several therapeutic properties. However, its high lipophilicity, metabolization, and instability impair its bioavailability and translational use in clinical settings. Several advanced drug delivery systems (ADDSs) have been evaluated as CBD carriers to overcome these drawbacks. These systems can improve the CBD dissolution profile, protect it against metabolization, and produce a site-specific release, increasing its bioavailability and making CBD administration clinically effective. AREAS COVERED: This review summarizes scientific reports on cannabidiol advanced delivery systems (CBD-ADSs) that have been (i) developed, and (ii) applied therapeutically; reports published in the main scientific databases until January 2020 were included. Studies without experimental data and/or published in languages other than English were excluded. Moreover, pharmaceutical technology tools in CBD therapeutic use have been discussed, emphasizing the clinical translation of CBD carrier use. EXPERT OPINION: Studies reporting CBD-ADS use for medicinal applications were reviewed and revealed multifaceted systems that can overcome the physicochemical drawbacks of CBD and improve its biological activities. Therefore, researchers concluded that the developed CBD-ADS can be used as an alternative to traditional formulations because they show comparable or superior effectiveness in treatment protocols. Although several criteria remain to be met, our findings emphasize the potential of CBD-ADSs for translational therapeutics, particularly for neurological-disorders.

Safety and Antioxidant Efficacy Profiles of Rutin-Loaded Ethosomes for Topical Application.

Topical application of dermocosmetics containing antioxidant and/or the intake of antioxidants through diet or supplementation are remarkable tools in an attempt to slow down some of the harmful effects of free radicals. Rutin is a strong antioxidant compound used in food and pharmaceutical industries. It was established that rutin presents a low skin permeation rate, a property that could be considered an inconvenience to the satisfactory action for a dermocosmetic formulation to perform its antioxidant activity onto the skin. Therefore, it is indispensable to improve its delivery, aiming at increasing its antioxidant capacity in deeper layers of the epidermis, being a possibility to associate the rutin to liposomal vesicles, such as ethosomes. Thus, in this work, the pre-clinical safety of rutin-loaded ethosomes was investigated employing an in vitro method, and the clinical safety and efficacy were also assessed. Rutin-loaded ethosomes were efficaciously obtained in a nanoscale dimension with a relevant bioactive compound loading (80.2%) and provided antioxidant in vitro activity in comparison with the blank sample. Pre-clinical and clinical safety assays assured the innocuous profile of the rutin-loaded ethosomes. The ethosomes containing the bioactive compound accomplished a more functional delivery system profile, since in the tape stripping assay, the deeper layers presented higher rutin amounts than the active delivered in its free state. However, the ex vivo antioxidant efficacy test detected no positive antioxidant activity from the rutin-loaded ethosomes, even though the in vitro assay demonstrated an affirmative antioxidant action.

Highly deformable and highly fluid vesicles as potential drug delivery systems: theoretical and practical considerations.

Vesicles that are specifically designed to overcome the stratum corneum barrier in intact skin provide an efficient transdermal (systemic or local) drug delivery system. They can be classified into two main groups according to the mechanisms underlying their skin interaction. The first group comprises those possessing highly deformable bilayers, achieved by incorporating edge activators to the bilayers or by mixing with certain hydrophilic solutes. The vesicles of this group act as drug carriers that penetrate across hydrophilic pathways of the intact skin. The second group comprises those possessing highly fluid bilayers, owing to the presence of permeation enhancers. The vesicles of this group can act as carriers of drugs that permeate the skin after the barrier of the stratum corneum is altered because of synergistic action with the permeation enhancers contained in the vesicle structure. We have included a detailed overview of the different mechanisms of skin interaction and discussed the most promising preclinical applications of the last five years of Transfersomes® (IDEA AG, Munich, Germany), ethosomes, and invasomes as carriers of antitumoral and anti-inflammatory drugs applied by the topical route.