Current pharmaceutical design最新文献

Background: Vascular endothelial dysfunction is the initial factor involved in cardiovascular injury in patients with diabetes. Retinoic acid is involved in improving vascular complications in patients with diabetes, but its protective mechanism is still unclear. This study aimed to evaluate the effect and mechanism of All-Trans Retinoic Acid (ATRA) on endothelial dysfunction induced by diabetes.

Methods: In the present study, streptozotocin (STZ)-induced diabetic rats and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs) were observed, and the effects of ATRA on HG-induced endothelial dysfunction and ferroptosis were evaluated.

Results: ATRA treatment improved impaired vasorelaxation in diabetic aortas in an endothelium-dependent manner, and this effect was accompanied by an increase in the NO concentration and eNOS expression. Ferroptosis, characterized by lipid peroxidation and iron overload induced by HG, was improved by ATRA administration, and a ferroptosis inhibitor (ferrostatin-1, Fer-1) improved endothelial function to a similar extent as ATRA. In addition, the inactivation of phosphoinositol-3-kinase (PI3K)/protein kinases B (AKT) and Yes-Associated Protein (YAP) nuclear localization induced by HG were reversed by ATRA administration. Vascular ring relaxation experiments showed that PI3K/AKT activation and YAP inhibition had similar effects on ferroptosis and endothelial function. However, the vasodilative effect of retinoic acid was affected by PI3K/AKT inhibition, and the inhibitory effects of ATRA on ferroptosis and the improvement of endothelial function were dependent on the retinoic acid receptor.

Conclusion: ATRA could improve vascular endothelial dysfunction by inhibiting PI3K/AKT/YAP-mediated ferroptosis induced by HG, which provides a new idea for the treatment of vascular lesions in diabetes.

Inflammation is a universal response of mammalian tissue to harm, comprising reactions to injuries, pathogens, and foreign particles. Liver inflammation is commonly associated with hepatocyte necrosis and apoptosis. These forms of liver cell injury initiate a sequence of events independent of the etiological basis for the inflammation and can result in hepatic disorders. It is also common for liver cancer. This review fundamentally focuses on the molecular pathways involved in hepatic inflammation. This review aims to explore the molecular pathways involved in hepatic inflammation, focusing on arachidonic acid, NF-κB, MAPK, PI3K/Akt, and JAK/STAT pathways. It investigates active compounds in herbal plants and their pharmacological characteristics. The review proposes a unique therapeutic blueprint for managing hepatic inflammation and diseases by modifying these pathways with herbal remedies.

Drug Delivery Systems (DDS) have been developed to address the challenges associated with traditional drug delivery methods. These DDS aim to improve drug administration, enhance patient compliance, reduce side effects, and optimize target therapy. To achieve these goals, it is crucial to design DDS with optimal performance characteristics. The final properties of a DDS are determined by several factors that go into formulating a pharmaceutical preparation. Thus, optimizing these factors can lead to the ideal DDS formulation. Artificial Neural Networks (ANN) are computational models that mimic the function of biological neurons and neural networks and perform mathematical operations on inputs to generate outputs. ANN is widely used in medical sciences for modeling disease diagnosis and treatment, dose adjustment in combination therapy, medical education, and other fields. In the pharmaceutical sciences, ANN has gained significant attention for designing and optimizing pharmaceutical formulations. This article reviews the use of ANN in the design and optimization of pharmaceutical formulations, specifically DDS. Since DDS is highly diverse, different factors are examined for each type of DDS. These factors are considered independent and dependent parameters for each ANN model, and various examples are provided. By utilizing ANN, it is possible to establish the relationship between the formulation factors and the resulting DDS characteristics, ultimately leading to the development of optimized DDS.

Objectives: The present review aims to discuss various strategies to overcome intracellular and extracellular barriers involved in gene delivery as well as the advantages, challenges, and mechanisms of gene delivery using non-viral vectors. Additionally, patents, clinical studies, and various formulation approaches related to lipid-based carrier systems are discussed.

Methods: Data were searched and collected from Google Scholar, ScienceDirect, Pubmed, and Springer.

Results: In this review, we have investigated the advantages of non-viral vectors over viral vectors. The advantage of using non-viral vectors are that they seek more attention in different fields. They play an important role in delivering the genetic materials. However, few nonviral vector-based carrier systems have been found in clinical settings. Challenges are developing more stable, site-specific gene delivery and conducting thorough safety assessments to minimize the undesired effects.

Conclusion: In comparison to viral vectors, nonviral vector-based lipid nanocarriers have more advantages for gene delivery. Gene therapy research shows promise in addressing health concerns. Lipid-based nanocarriers can overcome intracellular and extracellular barriers, allowing efficient delivery of genetic materials. Non-viral vectors are more attractive due to their biocompatibility, ease of synthesis, and cost-effectiveness. They can deliver various nucleic acids and have improved gene delivery efficacy by avoiding degradation steps. Despite limited clinical use, many patents have been filed for mRNA vaccine delivery using non-viral vectors.

The risk of illnesses is increasing in the modern era due to unhealthy and modern lifestyles. Research has shown that the most frequent acid-induced abrasion, which often occurs in the stomach and proximal duodenum, is gastric and Peptic Ulcer Disease (PUD), which is a primary worldwide health concern. The deformity is characterized by denuded mucosa and spreads into the submucosa. Non-steroidal antiinflammatory drugs (NSAIDs) and H. pylori infections are two common offenders. In the past, it has been thought that dietary variables, stress, and an acidic hypersecretory state encourage mucosal disruption in peptic acid disease patients. Peptic ulcers continue to be a significant health issue because of their potential for substantial consequences, including bleeding, blockage, and perforation, even with advancements in detection and treatment. This review discusses current screening methods for peptic ulcers and the challenges in diagnosis and treatment, emphasizing the need for precise diagnosis and more effective therapies.

Introduction: The incidence of Central Nervous System (CNS) disorders, including Parkinson's disease, Alzheimer's disease, stroke, and malignancies, has risen significantly in recent decades, contributing to millions of deaths annually. Efficacious treatment of these disorders requires medicines targeting the brain. The Blood-Brain Barrier (BBB) poses a formidable challenge to effective drug delivery to the brain, hindering progress in CNS therapeutics. This review explores the latest developments in nanoparticulate carriers, highlighting their potential to overcome BBB limitations.

Objective: This study aimed to evaluate and summarise the critical factors and pathways in the nanoparticle- based central nervous system's targeted drug delivery.

Methods: An extensive literature search was conducted, comprising the initial development of nanoparticle- based central nervous system-targeted drug delivery approaches to the latest advancements using various online search tools.

Results: The properties of nanoparticles, such as type of nanoparticles, size, shape, surface charge, hydrophobicity, and surface functionalisation, along with properties of the blood-brain barrier during normal and pathological conditions and their impact on the delivery of nanoparticles across the BBB, are identified and discussed here.

Conclusion: Important properties and pathways that determine the penetration of nanoparticles across the central nervous system are reviewed in this article, along with recent advances in the field.

With the development of microfluidics technology, it is now possible in medical biotechnology to examine clinical and rapid diagnostic operations involving pathogens, like bacteria and viruses. The method of separating bacteria from complicated homogeneous and heterogeneous samples is one of the most important steps in the diagnostic process. The microfluidic technology for bacterial separation offers a better and more promising platform by combining several physical properties and characteristics of bacteria. In contrast, the conventional method is time-consuming, limited to a few cell properties, and necessitates the completion of several challenging steps and processes involving skilled manpower. The microfluidics platform also has a number of advantages, including small-scale size, low cost, high efficiency, and simultaneous detection and execution of further steps. This enables cell separation, analysis, and experimental processing on a single chip. In this paper, we have analysed the mechanism of the bacterial separation process depending on phenocharacteristics along with their benefits, constraints, and applications. In addition, the performance metrics needed for the separation of the devices along with the challenges and future possibilities of developed devices, which are described in the literature, are discussed in detail. Thus, this review offers a holistic analysis of the separation of bacteria using microfluidic technology.

Introduction: Atherosclerosis refers to the thickening and hardening of artery walls. In our latest experiment, we utilized environmentally friendly techniques to produce multifunctional iron oxide nanoparticles (FeONPs) aimed at reducing inflammation in rats with atherosclerosis.

Method: The formulation was synthesized using curcumin (as the potent bioactive molecule) and was characterized. We assessed the in vitro antioxidant capability of the formulation against DPPH free radicals. Additionally, we quantified the mRNA levels of eNOS, PI3K, and AKT using Real Time-Polymerase Chain Reaction (RT-PCR). We tested the therapeutic impact of the bioactive formulation on a Triton X-100-induced atherosclerosis mouse model.

Results: The crystallinity and magnetic behavior confirmed the magnetic properties of the FeONPs. The DPPH assay exhibited the dose-dependent radical scavenging characteristics of FeONPs. In the animal experiments, significant upregulation of the studied genes was noticed in treated groups 2 and 3 compared to treated group 1. Moreover, the expression of PI3K/eNOS/Akt was greater in treated group 3 than in treated group 2. These results indicate a dose-dependent elevation in target gene expression.

Conclusion: Nevertheless, the variation in gene expression between the negative control and the untreated control was not statistically significant (p > 0.05) across all genes.

Introduction: Glyburide is a drug for the treatment of diabetes mellitus and has a potential effect on Alzheimer's disease. It is also a BCS Class 2 drug with low solubility and low permeability. Developing a nanosuspension formulation and increasing the solubility and dissolution rate of glyburide is required to overcome this challenge.

Methods: Thus, the goal of this work was to create glyburide nanosuspensions by ball milling and homogenizing glyburide to increase its solubility and rate of dissolution. To achieve this, the nanosuspension formulation was optimized using a central composite design. Zeta potential, particle size distribution and solubility were selected by way of dependent variables, and ball milling time, homogenization cycles, and Pluronic F-127/glyburide ratio were chosen as independent variables. Glyburide nanosuspensions were obtained with a particle size of 244.6 ± 2.685 nm. In vitro release and solubility studies were conducted following optimization.

Results: The saturation solubility of glyburide was nearly doubled as a result of the nanocrystal formation. Xray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FT-IR) were used to assess the nanosuspension. SEM images confirmed that the nanocrystal formation process was successful. Glyburide and the excipients have no incompatibilities, their physical states have not changed, and the preparation method has not affected the stability of glyburide, according to DCS, XRD, and FT-IR analyses.

Conclusion: These studies indicated that a combination of ball milling and homogenization techniques significantly enhanced the solubility of glyburide and its release from the formulation. Consequently, this approach can be applied to formulations characterized by low absorption and limited bioavailability.