Current Pharmaceutical Design - Online First

Ursolic acid, a natural pentacyclic triterpenoid compound, has been shown to have significant cardioprotective effects in various preclinical studies. This article reviews the various mechanisms by which ursolic acid achieves its cardioprotective effects, highlighting its potent anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Ursolic acid upregulates anti-oxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx), effectively reducing oxidative stress, thereby decreasing reactive oxygen species (ROS) and improving lipid peroxidation levels. Furthermore, ursolic acid downregulates pro-inflammatory cytokines and inhibits key inflammatory pathways, such as nuclear factor kappa B (NF-κB), which results in its anti-inflammatory effects. These actions help in protecting cardiac tissues from acute and chronic inflammation. Ursolic acid also promotes mitochondrial function and energy metabolism by enhancing mitochondrial biogenesis and reducing dysfunction, which is critical during ischemia-reperfusion (I/R) injury. Additionally, ursolic acid influences multiple molecular pathways, including B-cell leukemia/lymphoma 2 protein (Bcl-2)/Bcl-2 associated x-protein (Bax), miR-21/extracellular signal-regulated kinase (ERK), and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), to reduce cardiomyocyte apoptosis. Collectively, these properties make ursolic acid a promising therapeutic agent for cardiovascular diseases (CVDs), warranting further research and clinical trials to harness its potential fully.

Type 1 Diabetes is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells, leading to hyperglycemia and various complications. Despite insulin replacement therapy, there is a need for therapies targeting the underlying autoimmune response. This review aims to explore the mechanistic insights into T1D pathogenesis and the impact of delivery systems on immunotherapy. Genetic predisposition and environmental factors contribute to T1D development, triggering an immune-mediated attack on β-cells. T cells, particularly CD4⁺ and CD8⁺ T cells, play a central role in β-cell destruction. Antigen-specific immunotherapy is a unique way to modify the immune system by targeting specific antigens (substances that trigger the immune system) for immunotherapy. It aims to restore immune tolerance by targeting autoantigens associated with T1D. Nanoparticle-based delivery systems offer precise antigen delivery, promoting immune tolerance induction. Various studies have demonstrated the efficacy of nanoparticle-mediated delivery of autoantigens and immunomodulatory agents in preclinical models, and several patents have been made in T1D. Combining antigen-specific immunotherapy with β-cell regeneration strategies presents a promising approach for T1D treatment. However, challenges remain in optimizing delivery systems for targeted immune modulation while ensuring safety and efficacy.

Polymer and lipid-based nanocarriers are a state-of-art in nanomedicine and in co-drug delivery of drugs that could merges various diagnostic and treatment modalities such radiotherapy (RT), photodynamic therapy (PDT) and chemotherapy (CT) in cancer therapy. Among various shapes and nanostructures, polymer and lipid-based nanocarriers have the potential to carry two drugs in same time to cells. However, hydrophobic and hydrophilic drug can be loaded in between layers as well as in the core of these nanocarriers, simultaneously. This advantage of NPs can be employed in combination therapy. Radiosensitizer and photosensitizer agents play a critical role in radio-photodynamic therapy (RT-PDT) of cancer. Co-delivery of these agents to cancerous cells is advantageous to cancer therapy but still remain as a challenge of RT-PDT. However, in this review, we have highlighted the challenges of RT-PDT and role of polymer and lipid-based nanocarriers to co-delivery of hydrophobic and hydrophilic agents as radio-photosensitizers. Hence, the different kinds of Poly (lactic-co-glycolic acid) nanoparticles (NPs) have been categorized. Then, the biophysical mechanism of radio-photosensitizer agents with co-loading on polymer and lipid-based nanocarriers in RT-PDT treatment of cancer has been outlined. Finally, attention has been drawn to polymer and lipid-based nanocarriers in co- drugs delivery. Taken together, this work presents the latest updates on this area and highlighted the pros and cons of co-delivery for RT-PDT purposes.

The escalating prevalence of type 2 diabetes (T2DM) has emerged as a global public health dilemma. This ailment is associated with insulin resistance and heightened blood glucose concentrations. Despite the rapid advancements in modern medicine, where a regimen of medications is employed to manage blood glucose effectively, certain treatments manifest significant adverse reactions. Recent studies have elucidated the pivotal role of gallotannins in mitigating inflammation and obesity, potentially reducing the prevalence of obesity-linked T2DM. Gallotannins, defined by their glycosidic cores and galloyl groups, are ubiquitously present in plants, playing diverse biological functions and constituting a significant segment of water-soluble polyphenolic compounds within the heterogeneous tannins group. The structural attributes of gallotannins are instrumental in dictating their myriad biological activities. Owing to their abundance of hydroxyl groups (-OH) and complex macromolecular structure, gallotannins exhibit an array of pro-physiological properties, including antioxidant, anti-inflammatory, antidiabetic, protein-precipitating, and antibacterial effects. Extensive research demonstrates that gallotannins specifically obstruct α-amylase and pancreatic lipase, enhance insulin sensitivity, modulate short-chain fatty acid production, alleviate oxidative stress, exhibit anti-inflammatory properties, and influence the gut microbiota, collectively contributing to their antidiabetic efficacy. This review aims to consolidate and scrutinize the extant literature on gallotannins to furnish essential insights for their potential application in diabetes management.

Nanoparticles, defined as particles ranging from 1 to 100 nanometers in size, are revolutionizing the approach to combating bacterial infections amid a backdrop of escalating antibiotic resistance. Bacterial infections remain a formidable global health challenge, causing millions of deaths annually and encompassing a spectrum from common illnesses like Strep throat to severe diseases such as tuberculosis and pneumonia. The misuse of antibiotics has precipitated the rise of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Mycobacterium tuberculosis (MDR-TB), and carbapenem-resistant Enterobacteriaceae (CRE), underscoring the critical need for innovative therapeutic strategies. Nanotechnology offers a promising avenue in this crisis. Nanoparticles possess unique physical and chemical properties that distinguish them from traditional antibiotics. Their high surface area to volume ratio, ability to be functionalized with various molecules, and distinctive optical, electronic, and magnetic characteristics enable them to exert potent antibacterial effects. Mechanisms include physical disruption of bacterial membranes, generation of Reactive Oxygen Species (ROS), and release of metal ions that disrupt bacterial metabolism. Moreover, nanoparticles penetrate biofilms and bacterial cell walls more effectively than conventional antibiotics and can be precisely targeted to minimize off-target effects. Crucially, nanoparticles mitigate the development of bacterial resistance by leveraging multiple simultaneous mechanisms of action, which make it challenging for bacteria to adapt through single genetic mutations. As research advances, nanotechnology holds immense promise in transforming antibacterial treatments, offering effective solutions that address current infections and combat antibiotic resistance globally. This review provides a comprehensive overview of nanoparticle applications in antibacterial therapies, highlighting their mechanisms, advantages over antibiotics, and future directions in healthcare innovation.

In recent years, immunotherapy, namely immune checkpoint inhibitor therapy, has significantly transformed the approach to treating various forms of cancer. Simultaneously, the adoption of clinical oncology has been sluggish due to the exorbitant expense of therapy, the adverse effects experienced by patients, and the inconsistency in treatment response among individuals. As a reaction, individualized methods utilizing predictive biomarkers have arisen as novel strategies for categorizing patients to achieve successful immunotherapy. Recently, the identification and examination of circulating tumor cells (CTCs) have gained attention as predictive indicators for the treatment of cancer patients undergoing chemotherapy and for personalized targeted therapy. CTCs have been found to exhibit immunological checkpoints in several types of solid tumors, which has contributed to our understanding of managing cancer immunotherapy. Circulating tumor cells (CTCs) present in the bloodstream have a crucial function in the formation of metastases. Nevertheless, the practical usefulness of existing CTC tests is mostly restricted by methodological limitations.