In silico exploration of venlafaxine, a potential non-tricyclic antidepressant in a liposomal formulation for nose-to-brain drug delivery.

OBJECTIVE: Non-tricyclic antidepressants (non-TCAs) work by preventing the intake of norepinephrine and serotonin. Therefore, the aim of this study was to identify a potent non-TCAs and to develop liposomal formulation, characterize and to determine the drug release study across model of dialysis membrane via in vitro and in silico techniques. METHODS: The in silico docking analysis identified venlafaxine (VLF) as the best non-TCAs with the depressant targets (PDB ID: 3PBL and 4BVN). VLF-loaded liposomal formulation was prepared by the thin-film hydration technique and characterized by physicochemical properties, including entrapment efficacy, in vitro drug release, particle size analysis, and FTIR. Moreover, this article also compares VLF and VLF-loaded with liposome carriers (LPs) based on nose-to-brain drug delivery approaches to treating depression. RESULTS: Drug release profiles of the optimal liposomal formulation of VLF-LPs were examined in the high entrapment efficiency 94.13 ± 1.20% was attained at 224 nm, composed of spherical particles having a mean particle size of 191 ± 2.0 nm, a polydispersity index of 0.281 ± 0.06 and zeta potential of -20.3 mV. The best formulation of VLF-LPs was more effective than oral VLF treatment, as shown by the in vitro drug release data. CONCLUSION: The results show that the VLF-LPs formulation is a promising potential platform for application in nose-to-brain drug delivery. Thus, highlighting the robustness of the intranasal drug delivery system with enhanced pharmaceutical properties, efficacy, and bioavailability for the anti-depression effect.

Optimization of Nasal Liposome Formulation of Venlafaxine Hydrochloride using a Box-Behnken Experimental Design.

Background: Intranasal administration is among the most effective alternatives to deliver drugs directly to the brain and prevent first-pass metabolism. Venlafaxine-loaded liposomes are biocompatible carriers that enhance transport qualities over the nasal mucosa. Objective: This research aimed to develop, formulate, characterize, and observe the prepared formulation. Methods: The formulation was developed using the thin-film hydration technique. The response surface plot interrelationship between three independent variables are lipid, cholesterol and polymer and four dependent variables such as particle size, percentage entrapment efficiency, and percentage drug release were ascertained using the Box-Behnken design. Results: The drug-release chitosan-coated liposomes were reported to have a particle size distribution, entanglement efficiency, and 84%, respectively, of 191 ± 34.71 nm, 94 ± 2.71% and 94 ± 2.71%. According to in vitro investigations, liposomes as a delivery system for the nasal route provided a more sustained drug release than the oral dosing form. Conclusions: The intranasal administration of venlafaxine liposomal vesicles effectively enhanced the absolute bioavailability, retention time, and brain delivery of venlafaxine.

Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies.

The pathetic malignant mesothelioma (MM) is a extremely uncommon and confrontational tumor that evolves in the mesothelium layer of the pleural cavities (inner lining- visceral pleura and outer lining- parietal pleura), peritoneum, pericardium, and tunica vaginalis and is highly resistant to standard treatments. In mesothelioma, the predominant pattern of lesions is a loss of genes that limit tumour growth. Despite the worldwide ban on the manufacture and supply of asbestos, the prevalence of mesothelioma continues to increase. Mesothelioma presents and behaves in a variety of ways, making diagnosis challenging. Most treatments available today for MM are ineffective, and the median life expectancy is between 10 and 12 months. However, in recent years, considerable progress has already been made in understanding the genetics and molecular pathophysiology of mesothelioma by addressing hippo signaling pathway. The development and progression of MM are related to many important genetic alterations. This is related to NF2 and/or LATS2 mutations that activate the transcriptional coactivator YAP. The X-rays, CT scans, MRIs, and PET scans are used to diagnose the MM. The MM are treated with surgery, chemotherapy, first-line combination chemotherapy, second-line treatment, radiation therapy, adoptive T-cell treatment, targeted therapy, and cancer vaccines. Recent clinical trials investigating the function of surgery have led to the development of innovative approaches to the treatment of associated pleural effusions as well as the introduction of targeted medications. An interdisciplinary collaborative approach is needed for the effective care of persons who have mesothelioma because of the rising intricacy of mesothelioma treatment. This article highlights the key findings in the molecular pathogenesis of mesothelioma, diagnosis with special emphasis on the management of mesothelioma.