Scientia Pharmaceutica

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.

Accumulating evidence indicates extensive crosstalk between prostaglandin- and histamine-mediated signaling pathways. Histamine has been shown to induce COX-2 (Cyclooxygenase-2) expression and stimulate prostaglandin synthesis, whereas prostaglandins potentiate the vascular and inflammatory effects of histamine, creating a positive feedback loop that sustains inflammation. Based on these considerations, in silico molecular docking study of interaction of new cytisine and TGIQ (tetrahydroisoquinoline) derivatives with COX-2 and the histamine H₁ receptor was performed. Among the synthesized compounds, compound 1 exhibited the highest binding affinity toward Cyclooxygenase-2 (COX-2). Within the binding pocket of the human H₁ histamine receptor, the binding affinity profile differed markedly from that observed for COX-2, with compound 4 exhibiting the highest therapeutic potential and the strongest binding affinity, surpassing all reference compounds. The high anti-inflammatory efficacy of the studied compounds was confirmed in formalin- and histamine rat models. THIQ derivatives were shown to possess a higher anti-inflammatory index than cytisine derivatives. Comparative evaluation of the anti-inflammatory activity of isoquinoline and quinolizidine derivatives revealed that the isoquinoline derivatives possess marked anti-inflammatory properties combined with low toxicity, making them promising candidates for the development of novel, highly effective and safe anti-inflammatory agents for both oral and topical administration.