Current pharmaceutical design最新文献

Integrating the most advanced technologies in drug formulation and delivery systems is revolutionizing modern healthcare, leading to improved treatment efficacy and patient outcomes. This study explains how new technologies are transforming the way drugs are manufactured and delivered. They include the use of advanced materials, nanotechnology, and biotechnology. Nanotechnology has also enabled the fabrication of targeted drug-delivery particles. Such particles would guarantee that drugs reach a specific tissue or cell, with notable minimization of side effects. The precise targeting of drugs is found to significantly enhance the effectiveness of treatment in fields, such as oncology and personalized medicine, among others. Breakthroughs can also be observed in the design of biologics, gene therapies, and monoclonal antibodies, resulting in highly targeted treatments for a wide range of diseases. Besides novel drug formulations, smart delivery devices have also been designed that not only control the location and rate of drug release, but also the timing of drug release. These include implantable pumps, which ensure more controlled and sustained drug release, bio-responsive hydrogels, medication-eluting stents, which ensure controlled and sustained drug release, and many more devices. This reduces the number of readjustments and increases the likelihood of patient compliance with the treatment plan. This study also discusses the role of digital technologies, such as wearables and AI-driven drug delivery systems, which continue to track patient responses and dosages to improve the outcomes of therapy. Such developments have marked a significant paradigm shift in pharmaceutical research, bringing highly personalized, secure, and effective treatment options to patients worldwide.

Parkinson's disease (PD) is one of the severe neurodegenerative disorders characterized by a deficiency of dopamine in the substantia nigra. The implicated factors for this include mitochondrial dysfunction, gut dysbiosis, and alteration in the signaling pathways. Overall, these events lead to the generation and aggregation of misfolding proteins, i.e., Lewy bodies. These aggregates contribute to the production of oxidative stress, inflammation, and neurotransmission imbalance. Hence, impaired cognition and body movements in the PD patients. There are several conventional treatments, such as synthetic drugs and herbal drugs, used to mitigate PD. Despite having enormous potential, their use is limited due to their low permeability, low solubility, and complexation in standardization. However, with the advancement in technology, different NDDS (Novel drug delivery systems) such as vesicular drug delivery systems, SNEDDS (Self-Nanoemulsifying Drug Delivery System), NPs (Nanoparticles), NLCs (Nano-structure lipid carrier), SLN (Solid lipid nanoparticles), quantum dots, and dendrimers have been explored to overcome the limitations of conventional treatments. Hence, the present review emphasizes a brief introduction to PD, pathogenesis of PD, signaling pathways, biomarkers, conventional treatments, need for NDDS, and Applications of NDDS in PD. Additionally, patents, clinical trials, and ongoing clinical trials are also covered in the present manuscript.

Introduction: Jiaotai Pill (JTP) is a Traditional Chinese Medicine (TCM) prescription that has demonstrated therapeutic effects against Type 2 Diabetes Mellitus (T2DM). However, its active antidiabetic components and underlying mechanism of action remain unclear. This study aimed to identify the bioactive components in JTP and elucidate their molecular targets and therapeutic pathways in T2DM.

Methods: Chemical components of JTP were identified using ultra-high performance liquid chromatography coupled with Q-Exactive Orbitrap high-resolution mass spectrometer (UHPLC-Q-Exactive Orbitrap-HRMS) in both positive and negative ion modes. Data were processed with Compound Discoverer 3.2 (CD 3.2) data software and validated using literature sources. Network pharmacology analysis was performed via multiple databases, including the Traditional Chinese Medicine Systems Pharmacology Database, Uniport, PubChem, GenCards, String, and Cytoscape, to predict potential bioactive compounds and therapeutic targets. Key interactions were validated using molecular docking and molecular dynamics simulations.

Results: A total of 104 compounds were identified in JTP. Network pharmacology analysis revealed 5 key antidiabetic components and 5 core targets. These targets are involved in biological processes including apoptosis regulation, cell proliferation, and protein phosphorylation, and are enriched in pathways such as neuroactive ligand-receptor interaction, PI3K-AKT signaling, and AGE-RAGE signaling. Molecular docking indicated strong binding affinity between dihydrochelerythrine and AKT1(-9.0 kcal/mol) and TNF-α (-6.7 kcal/mol). Molecular dynamics simulation demonstrated stable and sustained hydrogen bonding between dihydrochelerythrine and AKT1.

Discussion: Dihydrochelerythrine, as an active ingredient in JTP, may exert its antidiabetic mechanism by binding with AKT1, but it needs to be verified by subsequent animal or cell experiments.

Conclusion: Dihydrochelerythrine, a key active component of JTP, may exert antidiabetic effects in T2DM through stable interaction with AKT1, highlighting a potential therapeutic mechanism.

Background: The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the urgent need for effective antiviral and anti-inflammatory therapies. Spiropyridine derivatives containing a chalcone moiety have shown potential in targeting key enzymes involved in viral replication and inflammation.

Objective: To evaluate the inhibitory effects of synthesized spiropyridine derivatives on SARS-CoV-2 main protease (Mpro), secreted phospholipase A2 (sPLA2), and cytosolic phospholipase A2 (cPLA2), and to assess their impact on inflammatory and oxidative stress markers in LPS-treated lung cells.

Aim: To develop novel therapeutic agents that can effectively manage COVID-19 and related inflammatory conditions.

Methods: The synthesized compounds (1-3) were tested for their inhibitory activity against SARS-CoV-2 Mpro, sPLA2, and cPLA2 using in vitro assays to determine IC50 values. Inflammatory markers (COX-2, IL- 2, IL-4, TGF-1β, TNF-α) and oxidative stress markers (GSH, SOD, GR, MDA) were measured in LPS-treated lung cells. Gene expression levels of sPLA2 and cPLA2 were also assessed. Molecular docking studies were conducted to analyze the binding affinities and interactions of the compounds with the target enzymes.

Results: Compounds 1-3 showed significant inhibitory activity against SARS-CoV-2 Mpro with IC50 values of 19.85 μM, 7.31 μM, and 3.73 μM, respectively. For comparison, baicalein's IC50 value was 13.63 μM. Additionally, these compounds inhibited sPLA2 with IC50 values of 8.36 μM, 7.31 μM, and 3.73 μM, and cPLA2 with IC50 values of 20.44 μM, 6.02 μM, and 4.61 μM, respectively. Baicalein's IC50 values for sPLA2 and cPLA2 were 11.73 μM and 5.89 μM, respectively. In LPS-treated lung cells, compounds 1-3 significantly reduced COX-2 by up to 90.12%, IL-2 by 74.19%, IL-4 by 79.51%, TGF-1β by 44.57%, and TNF-α by 68.49%. They enhanced GSH by up to 194%, SOD by 357.19%, and GR by 445.87%, while reducing MDA by 77.90%. Gene expression of sPLA2 and cPLA2 was significantly downregulated by up to 82.31% and 64.59%, respectively. Molecular docking studies revealed binding affinities of -28.20, -28.20, and -28.07 kcal/mol for SARS-CoV-2 Mpro; -16.72, -17.21, and -15.89 kcal/mol for sPLA2; and -65.66, -66.95, and - 79.24 kcal/mol for cPLA2, respectively.

Conclusion: The synthesized spiropyridine derivatives containing a chalcone moiety exhibit potent antiviral, anti-inflammatory, and antioxidant properties. These findings suggest that these compounds could be promising therapeutic agents for managing COVID-19 and related inflammatory conditions. Future studies should focus on in vivo experiments, clinical trials, and structural optimization to further develop these compounds for clinical use.

Introduction: Managing Type II Diabetes Mellitus (T2DM) can be extremely difficult, especially in diverse populations where patient outcomes may be impacted by gender differences. Understanding patients' knowledge, attitudes, and practices (KAP) is essential for creating focused interventions. This study aims to evaluate the KAP of T2DM patients attending outpatient clinics in Moga, Punjab, India, with a focus on gender disparities.

Methods: A cross-sectional study was conducted among 500 T2DM patients (197 females and 303 males). Inclusion criteria were T2DM patients aged above 18 years, while pregnant and breastfeeding women were excluded. Data were analyzed using SPSS version 25, applying the Mann-Whitney U, Kruskal-Wallis, Chisquare, and Spearman's correlation tests.

Results: Poor knowledge and attitude scores were observed in 32.8% and 37.4% of patients, respectively, while 51.7% displayed fair practice scores. A gender-wise analysis revealed that males had higher proportions of good knowledge (33.7%) and attitude scores (50.2%) compared to females (20.8% and 36.0%, respectively). In terms of practice, both genders reported similar poor scores (31%).

Discussion: Males had significantly higher knowledge and attitude scores, with better awareness of T2DM risk factors, complications, and management strategies, likely due to higher educational attainment and greater access to healthcare resources, but both genders faced challenges in translating knowledge into self-care practices. Correlation analysis revealed a positive association between KAP scores and clinical parameters.

Conclusion: The study underscores the need for tailored educational programs that incorporate socio-cultural considerations and improved access to healthcare resources, which are crucial for bridging gender gaps in diabetes self-management.

Introduction: Wound healing is a complex and dynamic biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. Conventional wound dressings provide only passive protection and fail to maintain an optimal healing microenvironment. Synthetic polymers, such as polyvinyl alcohol (PVA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), and polyethylene glycol (PEG), have emerged as promising materials in advanced wound care due to their tunable physicochemical properties, biocompatibility, and enhanced therapeutic functionality.

Aim: This review aims to evaluate the potential of synthetic polymers in wound healing applications, focusing on their structural and functional advantages, challenges, and opportunities in the development of nextgeneration wound dressings.

Methodology: A comprehensive literature review was conducted on recent developments in polymer-based wound dressings. In this review, we conducted a systematic literature search across Google Scholar, ScienceDirect, Scopus, Web of Science, and PubMed for publications between 2015 and 2025. The search strategy employed keywords, such as "wound healing", "polyvinyl alcohol", "polycaprolactone", "poly(lactic-coglycolic acid)", "polyethylene alcohol", "physicochemical characteristics", "drug delivery capabilities", and " clinical trial" to capture the research landscape.

Results: Synthetic polymers demonstrated significant potential in overcoming limitations of natural biomaterials, such as poor mechanical strength and rapid degradation. PEG-based hydrogels exhibited excellent hydrophilicity and sustained drug release. PCL scaffolds offered mechanical durability and supported tissue regeneration. PLGA allowed controlled therapeutic release through tunable degradation, while PVA ensured prolonged wound protection due to its structural stability. Polymer modifications, including crosslinking and blending, further enhanced wound healing efficacy.

Conclusion: Synthetic polymers provide versatile platforms for designing multifunctional wound dressings with improved healing outcomes. Future research should emphasize biodegradable, patient-specific, and smart wound dressings integrating controlled drug delivery, infection prevention, and angiogenic stimulation, thereby revolutionizing wound management practices.

In recent years, green tea (Camellia sinensis) has garnered significant attention for its potential health benefits, including its benefits for oral hygiene. Green tea contains several bioactive components, including catechins, polyphenols, and fluoride, which contribute to its antibacterial, anti-inflammatory, and antioxidant properties. This review examines the bioactive components of green tea, specifically catechins, polyphenols, and fluoride, which possess numerous biological effects, including oral health benefits. As a result of its ability to neutralize volatile sulfur compounds, green tea inhibits the growth of cariogenic bacteria, such as Streptococcus mutans, reduces plaque development, and inhibits the development of halitosis. Recent evidence suggests that epigallocatechin-3-gallate (EGCG) has significant potential for oral health benefits. Furthermore, its anti-inflammatory effects help reduce gingival inflammation and oxidative stress, thereby easing the symptoms of periodontal disease. Numerous studies have shown that EGCG inhibits the growth of oral squamous cell carcinoma through mechanisms that include the induction of oxidative stress and apoptosis in cancer cells, as well as the inhibition of tumor invasion. This review discusses the potential mechanisms by which green tea promotes oral health and its therapeutic applications in dentistry. The literature review suggests that green tea may have potential as an adjunctive therapy for preventing and managing dental complications. However, more comprehensive pre-clinical and clinical studies are necessary to validate its efficacy. Furthermore, factors such as individual variability, patients' oral health conditions, long-term outcomes, and alterations in the oral microbiome require thorough investigation.

Introduction: Millions of people have died from zoonotic illnesses, like COVID-19 and Nipah virus infection (NiV), throughout history. Fruit bats (Pteropus sp.) are the main reservoir host for NiV, an RNA virus belonging to the Henipavirus group, which causes extremely infectious illnesses, such as COVID- 19. NiV outbreaks have posed significant public health concerns, especially in South and Southeast Asia. The Nipah virus (NiV) infection is caused by a virus that belongs to the Paramyxoviridae family's Henipavirus genus. It is the source of zoonosis, which causes respiratory and neurological symptoms.

Methods: This study has reviewed the epidemiology, pathophysiology, genetic diversity, and phylogenetics of NiV. It has explored NiV's clinical features, cellular monitoring, infection factors, and the virus' reservoir host.

Results: Phylogenetic analysis has identified two circulating NiV lineages. Additionally, the study has examined the role of phytochemicals in combating viral infections. Despite the absence of a focused therapy for COVID-19, phytochemicals have been investigated for their potential antiviral properties. Evidence suggests that plants and their components may possess resistance against NiV by modulating the immune system and inhibiting viral replication.

Discussion: The investigation into plant-derived compounds has offered a novel direction for NiV treatment, potentially enhancing viral resistance through immune modulation. Continued research on natural antivirals could bridge current gaps in therapeutic options for emerging zoonotic diseases.

Conclusion: The study has highlighted the transmission risk, detection challenges, and the potential of phytochemicals in managing NiV infections. The therapeutic potential of plants and their antiviral properties offer promising insights into future treatments for serious viral diseases, like NiV.

A complicated anatomy comprising genetic, environmental, and lifestyle variables, cancer continues to be one of the top causes of death globally. Thanks to developments in molecular biology, the genetic mutations and epigenetic changes responsible for the onset and spread of cancer have been identified. Although our understanding of cancer biology has advanced significantly, therapy problems arise from the disease's heterogeneity. Surgery, chemotherapy, radiation, and targeted medicines are examples of modern therapeutic approaches that have increased survival rates but frequently have serious side effects and resistance problems. The complicated pathophysiology and essential location of brain cancer provide substantial hurdles. It encompasses both primary brain tumors and metastatic lesions. Gliomas, meningiomas, and medulloblastomas are examples of primary brain tumors that originate from distinct cell types within the brain, which differ in their aggressiveness and responsiveness to treatment. The most prevalent and aggressive type, known as glioblastoma multiforme (GBM), grows rapidly and is resistant to standard therapies. The diagnosis of brain cancer is now more accurate thanks to developments in neuroimaging and molecular diagnostics, which also allow for more precise tumor subtype identification and individualized treatment plans. Conventional therapies consist of radiation therapy, chemotherapy, and surgical resection; newer techniques, including immunotherapy and targeted therapies, are frequently added. In this review article, the pathophysiology of brain cancer, its diagnosis, and treatments using novel technology will be discussed. Moreover, it highlights FDAapproved drugs used in treating brain cancer, along with previous, ongoing, and future aspects in which modifications are made to enhance the efficacy of these drugs. This has been made possible due to advancements in nano-formulation techniques, which have enabled the development of novel drug delivery systems.

Introduction: This research aimed to reveal the role of antioxidants and DNMT1 gene expression in behavioral disorders after exposure to stress.

Methods: Forty-eight male and female mice (weight 25-35 grams) were used. Their pups (weight 18-22 grams) were divided into 6 groups (n=20), Control, Social isolation stress (SIS), and SIS + N-acetylcysteine (NAC) 150 mg/kg intraperitoneally for male and 3 similar groups for female subjects, eight mice from each group were used for the first-generation experiments and another for mating and producing the second generation. The second-generation pups were designated into 9 groups A to I. After conducting behavioral tests of the Morris water maze (MWM) and shuttle box, they were anesthetized, decapitated, and their brains were removed. The neuronal counts of CA1 and CA3 were performed. DNMT1 gene expression, total antioxidant capacity (TAC), and malondialdehyde (MDA) of the brain were measured.

Results: Spatial memory, passive avoidance, and TAC decreased in the SIS groups. MDA and DNMT1 gene expression of the SIS groups increased (p<0.001). Dead neurons in the CA1 and CA3 regions increased in the SIS group (p<0.001).

Discussion: According to the results of this study, N-acetylcysteine enhanced learning and memory while reducing neuronal death by decreasing oxidative stress. Additionally, it lowered the expression of the DNMT1 gene, which plays a crucial role in DNA methylation.

Conclusion: After studying the human population, N-acetylcysteine may be introduced as an adjunct therapy to help mitigate the effects of stress.