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Zinc oxide nanoparticles (ZnONPs) have shown antidiabetic activity in multiple studies and can be produced by different plant-mediated ("green") methods. This study aimed to compare ZnONPs prepared via different "green" approaches (heating at high temperatures (400 °C) vs. low temperature (70 °C)). The low temperature method involved addition of suspending agents (Tween 80 or gum arabic) and pH variations followed by lyophilization. The study evaluated the hypoglycemic potential of ZnONPs with the best properties (quantity of capped agents and stability) compared to the plant extract per se. The ZnONP synthesis involved a mixture of zinc nitrate hexahydrate as the zinc precursor and a plant extract with high antioxidant activity as the capping agent supplier. The results of the studies showed that the procedure using high-temperature heating resulted in almost uncapped nanoparticles with phytocompounds (0.01 % of phenolic compounds) and nanoparticle sizes larger than 300 nm. The low-temperature method produced ZnONPs with high retention of capping agents (92.90 % of phenolic compounds) and a size of approximately 200 nm. The use of Tween 80 with pH adjustment between 9 and 10 resulted in more stable nanoparticles than with gum arabic. These nanoparticles prepared with Tween 80, exhibited a pronounced in vivo antihyperglycemic activity at a much lower dose (10 mg ZnO/kg capped by 0.31 mg phenolic compounds per kg) than the extracts alone (400 mg extract/kg) following an oral glucose tolerance test. These results demonstrated that green-synthesized ZnONPs with a high retention rate of phytochemicals can induce antihyperglycemic effects at a low dose.

Diabetes is a metabolic pathology with chronic high blood glucose levels that occurs when the pancreas does not produce enough insulin or the body does not properly use the insulin it produces. Diabetes management is a puzzle and focuses on a healthy lifestyle, physical exercise, and medication. Thus far, the condition remains incurable; management just helps to control it. Its medical treatment is expensive and is to be followed for the long term, which is why people, especially from low-income countries, resort to herbal medicines. However, many active compounds isolated from plants (phytocompounds) are poorly bioavailable due to their low solubility, low permeability, or rapid elimination. To overcome these impediments and to alleviate the cost burden on disadvantaged populations, plant nanomedicines are being studied. Nanoparticulate formulations containing antidiabetic plant extracts or phytocompounds have shown promising results. We herein aimed to provide an overview of the use of lipid- and inorganic-based nanoparticulate delivery systems with plant extracts or phytocompounds for the treatment of diabetes while highlighting their advantages and limitations for clinical application. The findings from the reviewed works showed that these nanoparticulate formulations resulted in high antidiabetic activity at low doses compared to the corresponding plant extracts or phytocompounds alone. Moreover, it was shown that nanoparticulate systems address the poor bioavailability of herbal medicines, but the lack of enough preclinical and clinical pharmacokinetic and/or pharmacodynamic trials still delays their use in diabetic patients.

Low aqueous solubility and poor oral bioavailability are limiting factors in the oral delivery of voxelotor, an antisickling agent. To overcome these limitations, a voxelotor self-nanoemulsifying drug delivery system was developed. Various oils, surfactants, and cosurfactants were screened for their solubilization potential for the drug. The area of nanoemulsification was identified using a ternary phase diagram. An experimental mixture design and a desirability function were applied to select SNEDDSs that contain a maximum amount of lipids and a minimum amount of surfactant, and that possess optimal emulsification properties (i.e., droplet sizes, polydispersity index (PDI), emulsification time, and transmittance percentage). The optimized SNEDDS formulation was evaluated for the self-emulsifying time (32 s), droplet size (35 nm), and zeta potential (-8 mV). In vitro dissolution studies indicated a 3.1-fold improvement in drug solubility from the optimized SNEDDS over pure drug powder. After 60 min of in vitro lipolysis, 88% of the voxelotor loaded in the SNEDDS remained in the aqueous phase. Cytotoxicity evaluation, using Caco-2 cells, indicated the safety of the formulation at 0.9 mg/mL. The transport of the voxelotor SNEDDS across Caco-2 monolayers was significantly enhanced compared to that of the free drug. Compared to the drug suspension, the developed SNEDDS enhanced the oral bioavailability (1.7-fold) of voxelotor in rats. The results suggest that further development of SNEDDSs for the oral delivery of voxelotor is needed.