Enhanced Metabolic Syndrome Management Through Cannabidiol-Loaded PLGA Nanoparticles: Development and In Vitro Evaluation
- PMID: 40277882
- DOI: 10.1002/jbm.a.37916
Abstract
Cannabidiol (CBD) holds promise for managing metabolic diseases, yet enhancing its oral bioavailability and efficacy remains challenging. To address this, we developed polymeric nanoparticles (NPs), using poly(lactic-co-glycolic acid) (PLGA), encapsulating CBD using nanoprecipitation, aiming to create an effective CBD-nanoformulation for metabolic disorder treatment. These NPs (135-265 nm) demonstrated high encapsulation efficiency (EE% ≈ 100%) and sustained release kinetics. Their therapeutic potential was evaluated in an in vitro metabolic syndrome model employing sodium palmitate-induced HepG2 cells. Key assessment parameters included cell viability (MTT assay), glucose uptake, lipid accumulation (Oil Red O staining), triglycerides, cholesterol, HDL-c levels, and gene expression of metabolic regulators. Results showed an IC50 of 9.85 μg/mL for free CBD and 11.26 μg/mL for CBD-loaded NPs. CBD-loaded NPs significantly enhanced glucose uptake, reduced lipid content, lowered triglycerides and total cholesterol, and increased HDL-c levels compared to free CBD. Gene analysis indicated reduced gluconeogenesis via downregulation of PPARγ, FOXO-1, PEPCK, and G6Pase and enhanced fatty acid oxidation through CPT-1 upregulation. These findings suggest that CBD-loaded NPs may serve as a novel therapeutic strategy for the management of metabolic disorders, warranting further in vivo studies.
Keywords: antipsychotics, cannabidiol, diabetes, lipid metabolism, metabolic disorders, nanomedicine
© 2025 Wiley Periodicals LLC.
References
-
- D. C. Henderson, B. Vincenzi, N. V. Andrea, M. Ulloa, and P. M. Copeland, “Pathophysiological Mechanisms of Increased Cardiometabolic Risk in People With Schizophrenia and Other Severe Mental Illnesses,” Lancet Psychiatry 2, no. 5 (2015): 452–464, https://doi.org/10.1016/S2215‐0366(15)00115‐7.
-
- J. Vazquez‐Bourgon, J. Mayoral‐van Son, M. Gomez‐Revuelta, et al., “Treatment Discontinuation Impact on Long‐Term (10‐Year) Weight Gain and Lipid Metabolism in First‐Episode Psychosis: Results From the PAFIP‐10 Cohort,” International Journal of Neuropsychopharmacology 24, no. 1 (2021): 1–7, https://doi.org/10.1093/ijnp/pyaa066.
-
- A. M. Flores, N. Hosseini‐Nassab, K. U. Jarr, et al., “Pro‐Efferocytic Nanoparticles Are Specifically Taken Up by Lesional Macrophages and Prevent Atherosclerosis,” Nature Nanotechnology 15, no. 2 (2020): 154–161, https://doi.org/10.1038/s41565‐019‐0619‐3.
-
- M. Di Forti, D. Quattrone, T. P. Freeman, et al., “The Contribution of Cannabis Use to Variation in the Incidence of Psychotic Disorder Across Europe (EU‐GEI): A Multicentre Case‐Control Study,” Lancet Psychiatry 6, no. 5 (2019): 427–436, https://doi.org/10.1016/S2215‐0366(19)30048‐3.
-
- E. Setien‐Suero, O. Martinez‐Garcia, V. O. de la Foz, et al., “Age of Onset of Cannabis Use and Cognitive Function in First‐Episode Non‐Affective Psychosis Patients: Outcome at Three‐Year Follow‐Up,” Schizophrenia Research 201 (2018): 159–166, https://doi.org/10.1016/j.schres.2018.05.036.
MeSH terms
Substances
Grants and funding
- The authors especially thank the financial support from the Instituto de Investigación Sanitaria Valdecilla (IDIVAL; INNVAL18/30; INT22/00029) and Plan Estatal 2021-2023, Ministerio de Ciencia e Innovación (PID2021-122714OB-I00). J. V-B also acknowledges funding support from IDIVAL (INT/A21/10, INT/A20/04) and Plan Nacional sobre Drogas (Ministerio de Sanidad, Gobierno de España; 2021I079). L. M-N is particularly grateful to the Ministerio de Ciencia e Innovación for pre-doctoral funding (PRE2022-101521). Author
- INNVAL18/30/Instituto de Investigación Sanitaria Valdecilla
- INT22/00029/Instituto de Investigación Sanitaria Valdecilla
- INT/A21/10/Instituto de Investigación Sanitaria Valdecilla
- INT/A20/04/Instituto de Investigación Sanitaria Valdecilla
These promising results highlight the innovative potential of cannabinoid science in addressing metabolic health challenges. By enhancing CBD’s bioavailability through nanoparticle delivery, this research opens new doors for safer, more effective natural therapies. As exploration continues into the powerful relationship between cannabinoids and human physiology, studies like this offer hope for more accessible, plant-based solutions to support long-term metabolic wellness.

