Dual drug-loaded polymeric mixed micelles for ovarian cancer: Approach to enhanced therapeutic efficacy of albendazole and paclitaxel.

Chemotherapy resistance remains a significant challenge in treating ovarian cancer effectively. This study addresses this issue by utilizing a dual drug-loaded nanomicelle system comprising albendazole (ABZ) and paclitaxel (PTX), encapsulated in a novel carrier matrix of D-tocopheryl polyethylene glycol 1000 succinate vitamin E (TPGS), soluplus and folic acid. Our objective was to develop and optimize this nanoparticulate delivery system using solvent evaporation techniques to enhance the therapeutic efficacy against ovarian cancer. The formulation process involved pre-formulation, formulation, optimization, and comprehensive characterization of the micelles. Optimization was conducted through a 32 factorial design, focusing on the effects of polymer ratios on particle size, zeta potential, polydispersity index (PDI) and entrapment efficiency (%EE). The optimal formulation demonstrated improved dilution stability, as indicated by a critical micelle concentration (CMC) of 0.0015 mg/mL for the TPGS-folic acid conjugate (TPGS-FOL). Extensive characterization included differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FTIR). The release profile exhibited an initial burst followed by sustained release over 90 h. The cytotoxic potential of the formulated micelles was superior to that of the drugs alone, as assessed by MTT assays on SKOV3 ovarian cell lines. Additionally, in vivo studies confirmed the presence of both drugs in plasma and tumour tissues, suggesting effective targeting and penetration. In conclusion, the developed TPGS-Fol-based nanomicelles for co-delivering ABZ and PTX show promising results in overcoming drug resistance, enhancing solubility, sustaining drug release, and improving therapeutic outcomes in ovarian cancer treatment.

Wheat ergot fungus-derived and modified drug for inhibition of intracranial aneurysm rupture due to dysfunction of TLR-4 receptor in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a form of dementia that strikes elderly people more frequently than it does younger people. The cognitive skills and memory of Alzheimer's sufferers continue to deteriorate over time. Recent studies have shown that patients with AD have greater amounts of inflammatory markers in their bodies, which suggests that inflammation occurs early on in the progression of the disease. There is a possibility that Aß oligomers and fibrils can be recognised by TLRs, in addition to the microglial receptors CD14, CD36, and CD47. When Aß binds to either CD36 or TLR4, it sets off a chain reaction of inflammatory chemokines and cytokines that ultimately results in neurodegeneration. Diabetes and Alzheimer's disease have both been recently related to TLR4. The activation of TLR4 has been connected to a variety of clinical difficulties that are associated with diabetes, in addition to the internal environment of the body and the microenvironment of the brain. TLR4 inhibitors have been shown in clinical investigations to not only lessen the likelihood of getting sick but also to increase the average longevity. RESULT: In this work we used molecular docking and molecular dynamics modelling to investigate the effectiveness of FDA-approved antidiabetic plant derived drugs in combating the TLR4 receptor. Molecular docking experiments were used to make a prediction regarding the most important interactions involving 2-Bromoergocryptine Mesylate. With a binding affinity of -8.26 kcal/mol, it stood out from the other candidates as the one with the greatest potential. To verify the interaction pattern that takes place between 2-Bromoergocryptine Mesylate and the TLR4 receptor, a molecular dynamic simulation was run at a time scale of 150 nanoseconds. Because of this, 2-Bromoergocryptine Mesylate was able to make substantial contact with the active site, which led to increased structural stability during the process of the complex's dynamic development. CONCLUSION: As a result of this, the results of our research may be relevant for future research into the efficacy of 2-bromoergocryptine mesylate as a potential lead treatment for TLR4 receptors in intracranial aneurysm rupture in AD.