Improved Therapeutic Efficacy of CBD with Good Tolerance in the Treatment of Breast Cancer through Nanoencapsulation and in Combination with 20(S)-Protopanaxadiol (PPD)

Abstract

Cannabidiol (CBD), a nonpsychoactive major component derived from Cannabis sativa, widely used in neurodegenerative diseases, has now been proven to have growth inhibitory effects on many tumor cell lines, including breast tumors. Meanwhile CBD can effectively alleviate cancer-associated pain, anxiety, and depression, especially tumor cachexia, thus it is very promising as an anti-tumor drug with unique advantages. 20(S)-Protopanaxadiol (PPD) derived from the best-known tonic Chinese herbal medicine Ginseng was designed to be co-loaded with CBD into liposomes to examine their synergistic tumor-inhibitory effect. The CBD-PPD co-loading liposomes (CP-liposomes) presented a mean particle size of 138.8 nm. Further glycosyl-modified CP-liposomes (GMCP-liposomes) were prepared by the incorporation of n-Dodecyl β-D-maltoside (Mal) into the liposomal bilayer with glucose residue anchored on the surface to act as a ligand targeting the GLUT1 receptor highly expressed on tumor cells. In vivo studies on murine breast tumor (4T1 cells)-bearing BALB/c mice demonstrated good dose dependent anti-tumor efficacy of CP-liposomes. A high tumor inhibition rate (TIR) of 82.2% was achieved with good tolerance. However, glycosylation modification failed to significantly enhance TIR of CP-liposomes. In summary, combined therapy with PPD proved to be a promising strategy for CBD to be developed into a novel antitumor drug, with characteristics of effectiveness, good tolerance, and the potential to overcome tumor cachexia.

Phytocannabinoids: Exploring Pharmacological Profiles and Their Impact on Therapeutical Use

“…Nanoformulations with CBD With a focus on targeted drug delivery, nanoformulations like liposomes present promising avenues in pharmaceuticals. In a study by Fu et al, liposomes incorporating CBD and 20(S)-protopanaxadiol, along with glycosyl-modified co-loading liposomes, were developed to enhance the tolerability and efficacy of CBD in rats with breast cancer [91].…”

Nanoliposomes for Controlled Release of Cannabinodiol at Relevant Gastrointestinal Conditions

“…The CBD hydrogels reported by Dirksen et al 4 follow two complex stages: surfactant-assisted precipitation polymerization and CBD loading, requiring 10 expensive steps and at least 6 h of synthesis. Some studies have been published in the last year; among them, Fu et al, 7 Kok et al, 8 and Shilo-Benjamini et al 9 developed liposomes using CBD as an active ingredient. Although the aforementioned studies have evolved to in vivo evaluations, they differ in the difficulty of liposome synthesis, the indirect costs of the bioactive product, the lack of evaluations in human-simulated gastrointestinal conditions, and the size in a strictly nanometric regime found in the present work.…”