Miconazole nitrate (MIC) is an antifungal drug used for treatment of superficial fungal infections. However, it has low skin permeability. Hence, the objective of this study was to prepare miconazole nitrate using Transfersomes to overcome the barrier function of the skin. MIC Transfersomes were prepared using a thin lipid film hydration technique. The prepared Transfersomes were evaluated with respect to entrapment efficiency (EE%), particle size, and quantity of in vitro drug released to obtain an optimized formulation. The optimized formulation of MIC Transfersomes was incorporated into a Carbapol 934 gel base which was evaluated in comparison with a marketed product (Daktarin® cream 2%) for drug content, pH, spreadability, viscosity, in vitro permeation, and in vitro and in vivo antifungal activity. The prepared MIC Transfersomes had a high EE% ranging from (67.98 ± 0.66%) to (91.47 ± 1.85%), with small particle sizes ranging from (63.5 ± 0.604 nm) to (84.5 ± 0.684 nm). The in vitro release study suggested that there was an inverse relationship between EE% and in vitro release. The kinetic analysis of all release profiles was found to follow Higuchi’s diffusion model. All independent variables had a significant effect on the dependent variables (p-values < 0.05). The prepared MIC transfersomal gel showed higher antifungal activity than Daktarin® cream 2%. Therefore, miconazole nitrate in the form of Transfersomes has the ability to penetrate the skin, overcoming the stratum corneum barrier.

Hyperemia in response to neural activity is essential for brain health. A hyperemic response delivers O₂ and nutrients, clears metabolic waste, and concomitantly exposes cerebrovascular endothelial cells to hemodynamic forces. While neurovascular research has primarily centered on the front end of hyperemia—neuronal activity-to-vascular response—the mechanical consequences of hyperemia have gone largely unexplored. Piezo1 is an endothelial mechanosensor that senses hyperemia-associated forces. Using genetic mouse models and pharmacologic approaches to manipulate endothelial Piezo1 function, we evaluated its role in blood flow control and whether it impacts cognition. We provide evidence of a built-in brake system that sculpts hyperemia, and specifically show that Piezo1 activation triggers a mechano-feedback system that promotes blood flow recovery to baseline. Further, genetic Piezo1 modification led to deficits in complementary memory tasks. Collectively, our findings establish a role for endothelial Piezo1 in cerebral blood flow regulation and a role in its behavioral sequelae.

Despite considerable advances in cancer treatment, chemotherapy remains a cornerstone in breast cancer therapy. Therefore, reducing chemoresistance and adverse effects of chemotherapy is a priority. In this regard, Baicalin (BA) is the dominant natural flavonoid extracted from the roots of Scutellaria baicalensis showed fascinating antitumor activity in many types of cancers, including breast cancer. The present study aimed to explore the chemopreventive and antitumor action of baicalin alone and in combination with 5-FU in addition to its ability to enhance the antitumor effect of 5-FU on breast cancer using the Ehrlich solid tumor-mice model. A total of 70 female mice were divided into seven groups (1st group, saline group; 2nd group, DMSO group; 3rd group, BA+EST group; 4th group, EST group; 5th group, EST+5-FU; 6th group, EST+BA group; 7th group, EST+5-FU+BA).tumors were assessed by weight and histopathological examination. Inflammation, angiogenesis, and apoptosis were examined by ELISA, qRT-PCR, and immunohistochemical examinations. showed that pre-treatment with baicalin and treatment with baicalin and/or 5-FU significantly reduced inflammation and angiogenesis indicated by suppression of NF-kB/ IL-1β and VEGF amplification loop with marked elevation in apoptosis indicated by up-regulation of apoptotic caspase-3, pro-apoptotic p53, Bax and downregulation of anti-apoptotic Bcl-2. BA is a promising preventive or adjuvant therapy in breast cancer treatment with 5-FU mainly via cooperative inhibition of inflammation, angiogenesis, and triggering apoptotic cell death.

Objectives: The study aimed to prepare carbamazepine in solid lipid nanoparticle form (CBZ-SLN) in order to enhance its anticonvulsant effect. Method: Eight formulations of CBZ-SLNs were prepared by homogenization and ultra-sonication techniques. Results: The prepared CBZ-SLN showed a high entrapment efficiency% (39.66 ± 2.42%–71.91 ± 1.21%), a small particle size (45.11 ± 6.72–760.7 ± 5.25 nm), and a negative zeta potential (from −21.5 ± 1.02 to −38.4 ± 1.32 mv). The in vitro release study showed the slow release of CBZ from SLNs compared to CBZ aqueous dispersion (p < 0.05). The infrared spectroscopy and the thermal analysis revealed the compatibility of the drug with other ingredients and the presence of drug in the more soluble amorphous estate, respectively. The in vivo study on mice revealed that the CBZ-SLN had a higher anticonvulsant efficacy than CBZ aqueous dispersion after a lethal and chronic dose of pentylenetetrazole (PTZ) (p < 0.05). The histopathological examination of the hippocampus revealed a decrease in the percentage of degeneration in mice treated with the CBZ-SLN compared to the PTZ and CBZ groups. Conclusion: CBZ can be formulated as SLN with higher anticonvulsant activity than free CBZ aqueous dispersion.

Local renin-angiotensin systems exist in various malignant tumor tissues; this suggests that the main effector peptide, angiotensin II, could act as a key factor in tumor growth. The underlying mechanisms for the anti-angiogenic effect of angiotensin II type 1 receptor blockers need to be further evaluated. The present study was carried out to investigate the anti-angiogenic effect of olmesartan alone or in combination with sorafenib, an angiotensin (1–7) agonist or an angiotensin (1–7) antagonist in Ehrlich's ascites carcinoma-bearing mice. The tumor was induced by intradermal injection of Ehrlich's ascites carcinoma cells into mice. Tumor discs were used to evaluate the microvessel density; the serum levels of vascular endothelial growth factor (VEGF) and serum insulin-like growth factor I (IGF-I); and their intratumoral receptors, VEGF receptor-2 and IGF-I receptor, respectively. All parameters were determined following the treatment course, which lasted for 21 days post-inoculation. Monotherapy with olmesartan and its combination with sorafenib resulted in a significant reduction in microvessel density and serum levels of VEGF and IGF-I, as well as their intratumoral receptors. In addition, the combination of olmesartan (30 mg/kg) with an angiotensin (1–7) agonist reduced the microvessel density, IGF-I serum levels and the levels of its intratumoral receptor. In conclusion, olmesartan reduced the levels of the angiogenesis markers IGF-I and VEGF and down-regulated the intratumoral expression of their receptors in a dose-dependent manner, and these effects were dependent on the angiotensin (1–7) receptor. These results suggest that olmesartan is a promising adjuvant to sorafenib in the treatment of cancer.