Development and optimization of curcumin-loaded solid lipid nanoparticles using Box-Behnken design and evaluation of its efficacy in modulating morphine-induced conditioned place preference: in vivo and in silico studies

Drug addiction, particularly to opioids like morphine, remains a pressing global health issue. Curcumin, a natural flavonoid, holds promise for treating neurological disorders, yet faces challenges, such as poor solubility and limited bioavailability across the blood-brain barrier. Solid lipid nanoparticles offer a solution, facilitating drug delivery to the brain. Using the Box-Behnken design, nanoparticles were optimised, yielding particles sized 152 nm, with a polydispersity index of 0.254, and an encapsulation efficiency of 70.74%. These nanoparticles enhance curcumin concentration and retention in brain tissue. Behavioural experiments using the conditioned place preference (CPP) test confirmed curcumin's impact on morphine addiction and its modulation of c-Fos gene expression. Pharmacological network analysis identified potential mechanisms of action, highlighting common targets in calcium and serotonin pathways. Docking simulations showed curcumin's affinity for proteins like 5HT1A, MAO-A, and TRPV1, relevant to addiction pathways. This research underscores the potential of curcumin-loaded solid lipid nanoparticles as a therapeutic approach for combating opioid addiction and neurological disorders.