Scientia Pharmaceutica

Ionizing radiation induces oxidative and genotoxic stress through reactive oxygen and nitrogen species, resulting in cellular lipid and DNA damage. This study evaluated the radiomodifying activity of an ethanolic pomegranate peel extract (Punica granatum L.) using ex vivo Wistar rat liver homogenates and primary lymphocyte cultures. Liver homogenates were exposed to 1–6 Gy X-rays, and lipid peroxidation was assessed by malondialdehyde (MDA) levels. Lymphocyte cultures were exposed to 10 Gy and evaluated using the cytokinesis-block micronucleus assay. Post-irradiation treatment with 1250 µg/mL extract decreased the median MDA value from 42.3 to 27.1 nmol/g wet tissue, corresponding to a 35.9% reduction relative to the irradiated untreated control (p < 0.05). In irradiated lymphocyte cultures, treatment with 5, 2.5, and 0.1 mg/mL extract yielded median percentages of micronucleated binucleated cells of 32.0%, 38.0%, and 42.0%, respectively, compared with 56.0% in the irradiated untreated control. The significant reduction occurred at 5 mg/mL (42.9%; p < 0.001). No significant increase in this endpoint was observed in non-irradiated extract-treated cultures. These findings highlight the ex vivo models as a useful platform for preliminary screening of botanical extracts, bioactive compounds, and pharmaceutical formulations before in vivo evaluation.

Intranasal dry powder dosage forms have attracted interest in the last decade due to their advantages over liquid nasal dosage forms. These advantages include increased residence time in the nasal cavity, greater chemical stability and improved bioavailability for some drugs. Particle properties (e.g., particle size and morphology) of intranasal dry powder formulations play a vital role in the aerodynamic behaviour and consequently the deposition site of particles in the nasal cavity, which impacts drug delivery efficiency. Furthermore, the device used to administer the intranasal dry powder should be carefully selected, as it can influence particle deposition and ultimately therapeutic outcome. Certain challenges exist when evaluating the pharmacokinetic properties of intranasal dry powder formulations using in vitro and ex vivo models, such as uneven coverage of the epithelial surface and maintenance of membrane integrity. Furthermore, due to anatomical differences, some in vivo animal models may overestimate the drug delivery performance of intranasally administered dry powders (especially nose-to-brain drug delivery) and therefore have limited translational value. Although regulatory criteria for intranasal dry powders are available, specific and harmonised guidance on the formulation and evaluation of these dosage forms is still lacking. This review provides insights into key aspects of intranasal dry powder dosage forms, including formulation aspects, particle engineering strategies, the role of dry powder delivery devices, regulatory aspects and models available for the evaluation of the pharmacokinetic properties of intranasal dry powder dosage forms.

Type 2 diabetes mellitus (T2DM) has been associated with cognitive impairment and an increased risk of dementia in women. This study examined the effects of subchronic metformin treatment on recognition memory and brain pathology in female diabetic mice. T2DM was induced by streptozotocin and nicotinamide injections. Then, the mice received metformin (50, 150, or 250 mg/kg) orally for 28 days. Recognition memory was assessed using the Novel Object Recognition Test (n = 72). Biochemical analyses of whole-brain homogenates evaluated insulin, tau, and insoluble Aβ₄₂ (n = 4). Histological analyses evaluated neuronal damage and amyloid-like deposits in the hippocampal Cornu Ammonis 1 (CA1) region, cerebral cortex, and cerebellum (n = 4). The diabetic mice exhibited hyperglycemia, hyperinsulinemia, dyslipidemia, impaired recognition memory, and neuronal damage. Metformin reduced blood glucose levels and improved recognition memory. Metformin also normalized serum and brain insulin levels and reduced neuronal damage in the CA1 region, cortex, and cerebellum. Metformin reduced cerebellar Congo red-positive amyloid-like deposits and decreased insoluble Aβ₄₂ levels in whole-brain homogenates. However, at 250 mg/kg, metformin increased total and phosphorylated tau levels. These results suggest that metformin mitigates recognition memory deficits, attenuates neuronal damage, and reduces cerebellar amyloid-like deposits in female mice.