Lipid nanocapsules decorated and loaded with cannabidiol as targeted prolonged release carriers for glioma therapy: In vitro screening of critical parameters

Abstract

The therapeutic potential of cannabinoids has been truly constrained heretofore due to their strong psychoactive effects and their high lipophilicity. In this context, precisely due to the lack of psychoactive properties, cannabidiol (CBD), the second major component of Cannabis sativa, arises as the phytocannabinoid with the most auspicious therapeutic potential. Hence, the incorporation of CBD in lipid nanocapsules (LNCs) will contribute to overcome the dosing problems associated with cannabinoids.Herein, we have prepared LNCs decorated and loaded with CBD for glioma therapy and screened in vitro their critical parameters. On the one hand, we have encapsulated CBD into the oily core of LNCs to test their in vitro efficacy as extendedrelease carriers against the human glioblastoma cell line U373MG. The in vitro antitumor effect was highly dependent on the size of LNCs due to its pivotal role in the extent of CBD release. Effectively, a comparison between two differently-sized LNCs (namely, 20-nm and 50-nm sized carriers) showed that the smaller LNCs reduced by 3.0-fold the IC 50 value of their 50-nm sized counterparts. On the other hand, to explore the potential of this phytocannabinoid to target any of the cannabinoid receptors overexpressed in glioma cells, we decorated the LNCs with CBD. This functionalization strategy enhanced the in vitro glioma targeting by 3.4-fold in comparison with their equally-sized undecorated counterparts. Lastly, the combination of CBD-loading with CBD-functionalization further reduced the IC 50 values. Hence, the potential of these two strategies of CBD incorporation into LNCs deserves subsequent in vivo evaluation.

Characterization of Biological Material Adsorption to the Surface of Nanoparticles without a Prior Separation Step: a Case Study of Glioblastoma-Targeting Peptide and Lipid Nanocapsules

“…2c), indicating that the presence of LNCs in the filtrate would significantly interfere with the quantification of free peptide or protein using this quantification method (p = 0.005). The presence of LNCs in the filtrate has never been reported in previous publications (12,13,20,(23)(24)(25)(26)(27)(28).…”

“…to quantify their adsorption or encapsulation rates. This is particularly true for LNCs (12,(23)(24)(25)(26)(27)(28), and the studies of LNC/NFL peptide association (13,20,24). Generally, after separation using the devices, the BCA assay or liquid chromatography is used to quantify the proportion of free NFL peptide in the filtrate and the proportion of adsorbed NFL peptide at the LNC surface is then evaluated.…”

“…Not only used in biological research, these devices are often used to purify and/or separate nanoparticles from smaller molecules (biological materials, drugs, etc.) prior to their characterization, mainly due to their speed and ease of implementation (10)(11)(12)(13). More often than not, published studies reporting the use of this method do not show the controls used, raising doubts about the quality of the separation.…”

Dual-Purpose Materials Based on Carbon Xerogel Microspheres (CXMs) for Delayed Release of Cannabidiol (CBD) and Subsequent Aflatoxin Removal

“…The pharmaceutical field is one of the main areas of cannabinoid use due to its analgesic, hypotension, ocular, and antiemesis properties. In this sense, medications have been developed to treat neuropathic pains, traumas, cancer-related disorders, multiple sclerosis, nausea and vomiting induced by chemotherapy, Parkinson’s, Huntington’s disease, and Alzheimer’s disease, and current research is also focused on anorexia, dementia, Tourette’s syndrome, and fibromyalgia, among others [3].…”

“…Thus, different authors have studied the applications of CBD in the medical field, and have focused on improving the oral bioavailability of this compound as well as on nanocarriers [10]. Aparicio-Blanco et al [3] prepared monodisperse lipid nanocapsules (LNCs) as biocompatible and biodegradable materials modified and loaded with CBD for glioma therapy. The CBD was encapsulated onto LNCs to test in vitro efficacy, obtaining 20-nm and 50-nm nanoparticles.…”