Silybin (SLB), an important flavonoid from silymarin, displays significant hepatoprotective, anticancer, antioxidant, and neuroprotective effects. However, its therapeutic efficacy is limited by its low solubility and bioavailability. To address these challenges, we engineered bovine serum albumin (BSA) nanoparticles (NP) loaded with SLB (BSA-NP/SLB) using the coacervation method. BSA-SLB NP exhibited a spherical shape, a mean size of 197 nm, a polydispersity index of 0.275, a zeta potential of −34 mV, and an entrapment efficiency of 67%. X-ray diffraction analysis indicated amorphization of SLB upon encapsulation. Formulation stability was upheld over 180 days. In vitro release assays demonstrated controlled diffusion-erosion release, with approximately 40% SLB released within 0.5 h and 100% over 12 h. Intranasal administration of BSA-NP/SLB in rats improved SLB bioavailability by fourfold compared to free SLB. These findings highlight the promising potential of intranasally administered BSA-NP/SLB as an alternative approach to enhance SLB bioavailability, paving the way for innovative therapeutic applications.

Perillyl alcohol (POH), a bioactive monoterpenoid derived from limonene, shows promise as an antitumor agent for brain tumor treatment. However, its limited oral bioavailability and inadequate brain distribution hinder its efficacy. To address these challenges, this study developed nanostructured lipid carriers (NLCs) loaded with POH to improve its brain biodistribution. The NLCs prepared using hot homogenization exhibited an average diameter of 287 nm and a spherical morphology with a polydispersity index of 0.143. High encapsulation efficiency of 99.68% was achieved. X-ray diffraction analyses confirmed the semicrystalline state of POH-loaded NLCs. In vitro release studies demonstrated a biphasic release profile. Stability studies in simulated gastric and intestinal fluids confirmed their ability to withstand pH variations and digestive enzymes. In vivo pharmacokinetic studies in rats revealed significantly enhanced oral bioavailability of POH when encapsulated in the NLCs. Biodistribution studies showed increased POH concentration in brain tissue with NLCs compared with free POH, which was distributed more in non-target tissues such as the liver, lungs, kidneys, and spleen. These findings underscore the potential of NLCs as effective delivery systems for enhancing oral bioavailability and brain biodistribution of POH, providing a potential therapeutic strategy for brain tumor treatment.

Cannabinoid signaling has attracted increasing interest in diabetes because the endocannabinoid system regulates energy balance, glucose and lipid metabolism, inflammation, and tissue homeostasis. However, its therapeutic relevance remains uncertain. This study combined scientometric mapping with a critical synthesis of mechanistic, pharmacokinetic, and clinical evidence on cannabinoids and diabetes published between 2004 and 2024. A structured search of the Web of Science Core Collection identified 459 original research articles, which were analyzed using Bibliometrix and complementary visualization tools. Scientific production increased markedly after 2016 and became progressively more diversified, with growing prominence of inflammation, oxidative stress, cannabis exposure-related themes, and broader mechanistic and population-level research questions. Mechanistic evidence strongly implicates excessive peripheral CB1 signaling in hepatic lipogenesis, adipose dysfunction, impaired insulin responsiveness, and related metabolic abnormalities, whereas CB2-mediated effects remain context-dependent. Cannabidiol is supported mainly by preclinical evidence of anti-inflammatory, antioxidant, and tissue-protective activity rather than consistent glucose-lowering effects. Clinical translation is further constrained by formulation-dependent oral exposure, extensive first-pass metabolism, food effects, broad tissue distribution, drug-interaction potential, and interindividual variability. Clinical evidence remains limited: brain-penetrant CB1 blockade improved selected metabolic outcomes but was restricted by psychiatric toxicity, while cannabidiol has not demonstrated consistent glycemic efficacy. Overall, cannabinoid research in diabetes shows substantial mechanistic development but limited clinical convergence. Future progress will require compound- and target-specific strategies, peripheral or tissue-selective modulation, standardized formulations, exposure–response characterization, appropriate patient stratification, and clinically meaningful outcome assessment.