Tadalafil

Dhiman P, et al. Life Sciences, 2024, 123325.

This study highlights the neuroprotective potential of tadalafil in mitigating neurological impairments caused by hyperammonemia (HA). The investigation utilized a zebrafish larval model to evaluate tadalafil's effects on cognitive and locomotor deficits induced by HA.
HA was induced in zebrafish larvae via ammonium acetate exposure, while tadalafil treatment was administered to assess its therapeutic effects. Behavioral analyses demonstrated that tadalafil reversed HA-induced cognitive and locomotor impairments. Biochemical assays revealed normalized levels of gamma-aminobutyric acid (GABA), glutamate, and dopamine in the larval head, reflecting restored neurotransmitter homeostasis.
Gene expression studies further confirmed tadalafil's impact, with upregulation of neuroprotective genes (bcl2a, bdnf, grin1a, gria2b, drd1b, and drd2b) and downregulation of apoptotic (baxa) and GABA receptor-related genes (gabrz, gabrd, gabrg2). At the protein level, tadalafil treatment enhanced neuronal nitric oxide synthase (nNOS) activation and increased phosphorylation of CREB at Ser133, critical for neurogenesis and synaptic plasticity. These findings suggest that tadalafil indirectly modulates the nitric oxide pathway to attenuate HA-induced neurotoxicity. Its effects on neurotransmitter balance, apoptotic pathways, and neuronal signaling underscore its potential as a novel therapeutic agent for managing neurological deficits associated with HA.

Adeneye AA, et al. Toxicology Reports, 2024, 13, 101737.

This study investigates the protective role of tadalafil (TAD), a selective phosphodiesterase-5 inhibitor, against DOX-induced oxidative stress and inflammation in Wistar rats.
TAD pretreatment was administered orally to rats prior to intraperitoneal injections of DOX (2.5 mg/kg) over 12 days. DOX-induced hepatorenal toxicity was evidenced by significant biochemical disruptions, including increased serum levels of potassium, urea, and creatinine, alongside reduced bicarbonate and total calcium levels. Additionally, oxidative stress markers such as malondialdehyde (MDA) were elevated, while antioxidant enzyme activities, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), were significantly diminished. TAD pretreatment effectively ameliorated these toxic effects by restoring antioxidant enzyme activity, reducing oxidative stress, and modulating inflammatory cytokine levels. Histopathological analysis confirmed reduced tissue damage in the liver and kidneys. These findings highlight tadalafil's potential as a chemoprophylactic agent for mitigating DOX-induced hepatorenal toxicity.

Darweesh RS, et al. PHARMACIA, 2024, 71, 1-15.

The preparation of tadalafil (TDA) nanocrystals (NCs) offers a promising approach to improve its solubility and bioavailability for intranasal delivery. This study employs the sonoprecipitation technique to produce TDA NCs, optimizing their physicochemical properties through the use of cryoprotectants and stabilizers.
The organic phase, consisting of TDA dissolved in dimethyl sulfoxide (DMSO) at 20 mg/mL, was combined with an aqueous antisolvent phase containing cryoprotectants such as glucose or trehalose. Stabilizers including Tween, polyvinyl alcohol (PVA), and Pluronic F68 were tested at varying ratios to the drug. The organic solution was added dropwise to the aqueous phase under controlled stirring and ultrasonication, promoting the formation of nanosized crystals.
Nanosuspensions were purified through centrifugation and lyophilized into stable dry powders. The control formulation, lacking stabilizers or cryoprotectants, demonstrated inferior stability and dispersibility compared to stabilized formulations. PVA-stabilized TDA NCs, prepared at an elevated temperature, exhibited enhanced particle size uniformity and stability.