Self-Assembly System Based on Cyclodextrin for Targeted Delivery of Cannabidiol

Abstract

Cannabidiol (CBD) is one specific kind of the cannabinoid in Cannabis sativa L with a wide range of pharmacological activities. However, the poor water solubility and specificity of CBD limits its application in pharmaceutical field. For solving these problems, in this work, we successfully prepared a targeted carrier by grafting biotin (BIO) onto ethylenediamine-β-Cyclodextrin (EN-CD) in a single step to generate a functionalized supramolecule, named BIO-CD. Subsequently, an amantadine-conjugated cannabinoids (AD-CBD) was prepared and self-assembled with the BIO-CD. A series of methods were used to characterize the inclusion behavior and physicochemical properties of AD-CBD and BIO-CD. The results showed that AD-CBD entered the cavity of BIO-CD and formed a 1:1 host-guest inclusion complex. MTT assay and confocal laser scanning microscopy (CLSM) revealed that the targeting effect and anticancer activity of AD-CBD/BIO-CD inclusion complex against three human cancer cell lines were higher than BIO-CD, AD-CBD and free CBD. Moreover, the inclusion complex could release drugs under weakly acidic conditions. These results demonstrated that AD-CBD/BIO-CD inclusion complex possess excellent targeted and anticancer activity, which is hopeful to be applied in clinic as a new therapeutic approach.

Cannabidiol-Loaded Solid Lipid Nanoparticles Ameliorate the Inhibition of Proinflammatory Cytokines and Free Radicals in an In Vitro Inflammation-Induced Cell Model

“…The comparison between CBD and CBD-SLNs diffraction indicates a notable distinction. The analysis of pure CBD displayed a sequence of sharp diffraction peaks between 2θ values of 5 • and 30 • , consistent with various research findings that show its crystalline properties [45,46]. Importantly, these characteristic peaks were not observed in the XRD pattern of the CBD-SLNs.…”

Physiologically based pharmacokinetic modeling and simulation of cannabinoids in human plasma and tissues

“…PBPK models for intravenous infusion of 20 mg and oral administrations of 5.4, 10, and 30 mg of CBD were developed. The oral formulations were set as immediate release suspension with a mean particle radius of 10 μm and stomach transit time of 0.1 h. Water solubility of CBD was reported to be 6.27 × 10 −5 mg/ml at pH 7.0 in the literature (Mannila et al, 2007; Zhu et al, 2021), which was input into the PBPK model. All other physicochemical and pharmacokinetic properties of CBD were predicted by QSAR models (Table S1) and input into the PBPK model.…”

Current Challenges and Opportunities for Improved Cannabidiol Solubility

“…Cyclodextrins can accommodate small organic molecules like CBD within their lipophilic central cavity, resulting in water-soluble CBD inclusion complexes with an apparent solubility of up to 5000 µg/mL. Several studies have also investigated the efficacy of different isoforms of cyclodextrin, such as α-CDs, β-CDs, and γ-CDs [47,[66][67][68][69][70][71][72]. The water solubility of CDcannabinoid complexes can be further improved by chemically derivatizing β-CD.…”