Current Drug Targets - Online First

Aging is a complex biological process marked by progressive cellular and tissue decline, leading to an increased risk of age-related diseases. Plant-based natural compounds, including polyphenols, flavonoids, carotenoids, alkaloids, and terpenoids, have gained attention for their potential in mitigating aging-related damage through antioxidant, anti-inflammatory, and cellular repair mechanisms. The review identified that plant-derived bioactive compounds target key pathways involved in aging, including Sirtuins (SIRT1), AMP-activated protein kinase (AMPK), and Nuclear Factor-kappa B (NF-κB). These compounds address key hallmarks of aging, such as oxidative stress, mitochondrial dysfunction, cellular senescence, and chronic inflammation. Evidence suggests their potential in preventing or delaying age-related disorders, including neurodegenerative diseases, cardiovascular conditions, and skin aging. Plant-derived compounds offer a promising alternative to synthetic anti-aging interventions due to their efficacy, safety, and sustainability. However, challenges such as low bioavailability and limited clinical validation must be addressed. Advances in drug delivery systems and comprehensive clinical trials are critical to realizing their full therapeutic potential. Plant-based bioactive compounds represent a significant opportunity for developing safer and more sustainable anti-aging therapies. Continued research is essential to overcome existing limitations and facilitate the integration of these approaches into mainstream healthcare practices.

Digital twin technology has emerged as a breakthrough development in healthcare, providing personalised transdermal drug delivery systems for chronic pain treatment. Digital twins provide accurate, customised therapy to enhance therapeutic outcomes and reduce risks by combining patient-specific computational models. This article aims to explore the applicability of digital twin technology in improving the transdermal delivery of drugs for successful chronic pain management. It is enabling personalised treatment through patient-specific simulations. By integrating physiological data with computational models, digital twins optimise drug absorption, patch application, and dosage adjustments in real-time, enhancing therapeutic outcomes while minimising side effects. Recent advancements highlight improvements in fentanyl patch optimisation, site-specific drug delivery, and thermally controlled systems. However, challenges such as ethical concerns, data security, and standardisation need to be addressed. Future research should focus on integrating AI and IoT to refine digital twin applications in precision medicine. It can be concluded from the findings of various studies that digital twin technology offers a promising future for precise and individualised transdermal drug delivery in chronic pain, paving the way for safer and more effective therapeutic interventions.

Lung cancer, particularly non-small cell lung cancer, is a leading cause of global mortality, with many cases diagnosed at advanced stages. The Toll-Like Receptor (TLR) signaling pathway plays a crucial role in linking inflammation to lung cancer progression, with both pro-tumor and anti-tumor effects. This perspective delves into the complex functions of TLR proteins in lung cancers, elucidating their involvement in tumor growth, angiogenesis, and metastasis. In addition, we highlight the therapeutic potentials of TLR agonists and antagonists, emphasizing their interplay with immune checkpoint inhibitors like PD-1/PD-L1 blockers to overcome immunosuppressive barriers. Nevertheless, the paradoxical effects of TLR activation, balancing immune stimulation and suppression, demand precise targeting strategies. Collectively, our study synthesizes the current understanding of TLR signaling pathways in lung cancers, offering insights into their potential for advancing lung cancer therapies.

Amylin is a thirty-seven amino acid peptide hormone that is secreted from the pancreas with insulin. The peptide hormone amylin activates its receptors in the brain to regulate blood glucose and food appetite. Interestingly, the amylin receptor is the heterodimer of the calcitonin receptor (which is the receptor for the peptide hormone calcitonin) and an accessory protein called receptor activity-modifying protein. Amylin receptor activation has emerged as a promising drug target for the treatment of diabetes and obesity. Recent pharmaceutical efforts with amylin receptor activators have focused on developing drugs for the treatment of obesity. Multiple amylin analogs have been tested in pre-clinical settings, and some are currently being tested in clinical trials. For this review, recent research publications and available information regarding drug development targeting amylin receptors were collected. This review summarizes the amylin receptor activators currently being tested in clinical trials for the treatment of obesity. In addition, recent research achievements were demonstrated, such as the introduction of mutations that enhanced receptor affinity/potency and the development of a method for measuring selective amylin receptor activation. Potential issues along with peptide drug development were described, including lipidation to achieve a long-acting property. The combination of an amylin analog and other anti-obesity peptide drugs has demonstrated higher clinical efficacy in reducing body weight than monotherapy. The combination therapy is likely to be the first drug therapy where an amylin analog is used for obesity treatment. In addition, amylin receptor activators may have an adverse effect profile more favorable than that of GLP-1 receptor activators, which could be a potential benefit of amylin receptor activators.

Numerous bladder-related diseases, including urinary blockages, interstitial cystitis, overactive bladder syndrome, cancer, and infections of the urinary tract, can affect bladder function. The human urinary bladder's distinct anatomy successfully prevents any hazardous material from entering circulation. The pathogenesis was assessed according to the extent of invasion in the bladder wall tissue obtained through Transurethral Resection of Bladder Tumor (TURBT) and classified as Muscle-Invasive and Non-Muscle Invasive Bladder Cancer (MBIC and NMIBC). Intravesical Drug Delivery (IDD) has recently gained attention for treating bladder disorders. IDD refers to the insertion of a drug directly into the bladder using a catheter. Intravesical administration of immunotherapy or chemotherapy has been demonstrated to reduce recurrence rates and inhibit disease progression. In addition, several other systems, including recombinant BCG, gene therapy, vectors, and Antibody-Drug Conjugates (ADCs), are now used. Moreover, the novel intravesical formulations of distinct chemotherapeutic agents, including gemcitabine, Doxorubicin (DOX), and Mitomycin C (MMC), are used in bladder-related problems. Novel intravesical drugs, polymeric hydrogels, dendrimers, hydrogels, mucoadhesives, nanocarriers, and intravesical devices have been discussed. Aside from chemotherapy and immunotherapy, devices such as GemRIS, device-assisted hyperthermic intravesical chemotherapy, and photodynamic therapy are utilized.

Poor solubility remains a significant obstacle in drug administration, adversely affecting the bioavailability and therapeutic efficacy of many drugs. It is also recognized as a primary factor contributing to issues with bioavailability, such as poor, inconsistent, limited, and highly variable bioavailability of marketed products. It is estimated that 40% of marketed drugs face bioavailability challenges primarily due to poor water solubility, and about 90% of pharmacological compounds exhibit poor water solubility in their early development stages. Addressing this issue is crucial for improving drug performance, efficacy, and patient outcomes. This review provides an overview of the challenges associated with poorly soluble drugs, including low bioavailability, limited dissolution rates, inconsistent absorption, decreased patient compliance, formulation difficulties, and associated costs and time constraints. Numerous strategies have been now investigated to tackle the issue of poor solubility. This review offers an updated overview of commonly used macro and nano drug delivery systems, including micelles, nanoemulsions, dendrimers, liposomes, lipid-based delivery systems, microemulsions, cosolvents, polymeric micelle preparation, drug nanocrystals, solid dispersion methods, crystal engineering techniques, and microneedle-based systems. Additionally, the review examines advanced techniques like cyclodextrin-based delivery systems, co-solvency and co-crystallization approaches, polymeric micelles, spray drying, co-precipitation, and amorphous solid dispersion. The role of computational modeling and formulation prediction is also addressed. Recent advancements in protein-based approaches, 3D printing, mesoporous silica nanoparticles, supramolecular delivery systems, magnetic nanoparticles, nanostructured lipid carriers, and lipid-based nanoparticles are highlighted as novel solutions for enhancing the solubility of poorly soluble drugs. The review concludes with predictions for the future, emphasizing the potential for further innovation in drug delivery methods to overcome the challenges associated with poorly soluble drugs.