Formulation of Nanomicelles Loaded with Cannabidiol as a Platform for Neuroprotective Therapy

Abstract

The present study is focused on the development of cannabidiol-loaded polymeric nanomicelles as a drug delivery system with neuroprotective effects. Cannabidiol was loaded in Pluronic micelles (Pluronic P123 or its combination with Pluronic F127) possessing an average diameter smaller than 50 nm and high encapsulation efficiency for the hydrophobic drug (80% and 84%, respectively). The successful encapsulation and transformation of cannabidiol in amorphous phase were observed by IR spectroscopy and X-ray diffraction, respectively. Studies with neuroblastoma cells (SH-SY5Y and Neuro-2a) showed that the pure cannabidiol caused a dose-dependent reduction of cell viability, whereas its loading into the micelles decreased cytotoxicity. Further, neuroprotective effects of pure and micellar cannabidiol were examined in a model of H2O2-induced oxidative stress in both neuroblastoma cells. The pre-treatment of cell lines with cannabidiol loaded into the mixed Pluronic P123/F127 micelles exerted significantly stronger protection against the oxidative stress compared to pure cannabidiol and cannabidiol in single Pluronic P123 micelles. Interestingly, the empty mixed P123/F127 micelles demonstrated protective activity against the oxidative stress. In conclusion, the study revealed the opportunity to formulate a new drug delivery system of cannabidiol, in particular nanosized micellar aqueous dispersion, that could be considered as a perspective platform for cannabidiol application in neurodegenerative diseases.

Double-Loaded Doxorubicin/Resveratrol Polymeric Micelles Providing Low Toxicity on Cardiac Cells and Enhanced Cytotoxicity on Lymphoma Cells

“…The combination of Pluronics with different hydrophiliclipophilic balance (HLB) values (8 and 22, respectively) was believed to ensure an efficient loading of both drugs. The micelles were prepared at a ratio 1:1 (wt/wt) between the copolymers, since a previous study showed their high stability [40]. The double drug loading was performed via the film hydration method.…”

“…Thus, taking into consideration both the values of the Flory-Huggins parameter (Figure 1b) and the partition coefficients (Figure 2a,b), we suggested that resveratrol was most probably loaded into the micellar core, whereas doxorubicin was located in the shell (Figure 2c). the copolymers, since a previous study showed their high stability [40]. The double drug loading was performed via the film hydration method.…”

“…Wei et al observed that P-gp inhibition by Pluronic copolymers is associated with the reduction of intracellular adenosine triphosphate (ATP) [31]. Encapsulation in Pluronic micelles has been reported to successfully improve the unfavourable physicochemical and biopharmaceutical characteristics of various drugs, in particular paclitaxel [32,33], lacidipine [34], isoliquiritigenin [35], niclosamide [36], sorafenib and verteporfin [37], curcumin [38,39], and cannabidiol [40].…”

Cannabinoids: Potential for Modulation and Enhancement When Combined with Vitamin B12 in Case of Neurodegenerative Disorders

“…Their therapeutic potential, similar to the benefits of omega-3 in slowing amyotrophic lateral sclerosis (ALS), is noteworthy due to cannabinoids’ complexity, which is visible in the regularities of improvement under omega-3 fatty acids’ [ 2 ] impact as well as dependency on vitamin B12 deficiency [ 3 ]. Advances include β-caryophyllene nanoparticles targeting cannabinoid receptor 2 (CB 2 R) [ 4 ] and a micellar system for cannabidiol delivery with high encapsulation efficiency [ 5 ]. Maintaining homeodynamics is essential, as disturbances can lead to disorders, contributing to neurotoxicity and inflammation linked with lipid metabolism impairment that might be involved in alterations associated with neurodegenerative disorders, highlighting the hypothesis of their being secondarily a lipid-metabolism-associated disorder.…”

“…After describing ECS and its receptors and cannabinoids as well as the relation between aggregation and microglial dysfunction, the focus will be put on Section 3 , indicating that it can be hypothesized, given the enhancing effects of CBD observed alongside vitamin B12 in the treatment of MS, that a combination of CBD with vitamin B12 might prove beneficial for neurodegeneration improvement. Particularly when this combination is incorporated within a micellar system, as proposed by Yordanov et al (2022) [ 5 ], it aims at increasing the therapeutic potential.…”