Current pharmaceutical design最新文献

Transdermal Drug Delivery (TDD) has emerged as a promising alternative to conventional routes of administration, offering controlled drug release, improved bioavailability, and patient compliance. Recent advancements in formulation strategies, penetration enhancers, and novel carrier systems have significantly enhanced the efficacy of transdermal drug delivery. This review comprehensively discusses the fundamental principles, advantages, and limitations of TDD while exploring innovative approaches, including Microneedles (MN), nanoformulations, and iontophoresis, to overcome skin permeability barriers. Furthermore, we highlight recent advancements in polymeric systems and bioresponsive technologies that have revolutionized transdermal therapeutics. Despite notable progress, challenges such as drug stability, skin irritation, and limited drug permeability persist. Addressing these concerns through interdisciplinary research and technological innovations is crucial for further expanding the scope of TDD. This review provides an in-depth analysis of current trends, challenges, and future perspectives to advance transdermal therapeutic systems for enhanced clinical applications.

Adverse Drug Reactions (ADRs) pose significant challenges to patient safety, healthcare systems, and public health worldwide. As the pharmaceutical landscape expands with complex therapies such as biologics and biosimilars, the need for robust pharmacovigilance systems has become paramount. This review provides a comprehensive overview of ADRs, their classification, underlying mechanisms, and associated clinical and economic impacts. It explores global pharmacovigilance frameworks, including the WHO Programme for International Drug Monitoring, and examines the roles of major regulatory bodies such as the FDA, EMA, CDSCO, and MHRA in ensuring drug safety. Special emphasis is placed on the challenges faced by developing countries, including underreporting and inadequate infrastructure, alongside strategies to overcome these barriers through capacity building and technology integration. The review also highlights advancements in pharmacovigilance methodologies, including the application of artificial intelligence, big data analytics, blockchain, and IoT devices, to enhance ADR detection, reporting, and management. Case studies and regional pharmacovigilance systems are analyzed to illustrate best practices and areas for improvement. Additionally, the role of pharmacovigilance in the context of the COVID-19 pandemic underscores the necessity for adaptive frameworks during global health crises. By addressing current challenges and emerging trends, this review aims to provide actionable insights to improve drug safety monitoring and foster global cooperation in pharmacovigilance practices.

Herpes zoster, also known as shingles, is caused by the reactivation of the Varicella-Zoster Virus (VZV), which remains dormant in the cranial sensory nerve ganglia and spinal dorsal root ganglia after the initial VZV infection is cured in a patient. When it reactivates, it travels down the nerve to the skin, causing a painful rash and blisters. The pathophysiology involves viral replication in nerve cells, inflammation, and subsequent skin lesions. Herpes zoster can have a significant impact on an individual's physical, psychological, and social well-being. While the condition is usually not life-threatening, it can cause painful and debilitating complications. Herpes zoster can cause significant morbidity, primarily due to Postherpetic Neuralgia (PHN), a persistent neuropathic pain condition. While acute pain during the initial HZ rash can be intense, PHN can be debilitating and significantly impact a patient's quality of life. Other complications, though less common, can include vision loss, neurological problems, and secondary bacterial infections. Herpes zoster (HZ), which has a lifelong risk of 20 to 30% that rises with age, is a prevalent disease in the elderly and immunocompromised patients and leads to increased healthcare costs. The primary goals of HZ management are to minimize and prevent Postherpetic Neuralgia (PHN) and Zoster-Associated Pain (ZAP), as well as to promote a speedy recovery from the viral infection. The treatment of infection requires the use of antivirals that combat viral replication. However, only a few antivirals, such as acyclovir, famciclovir, valacyclovir, amenamevir, and brivudine, have clinical licenses for the treatment of HZ. Thankfully, several novel HZ medications have been proposed and studied, including new antivirals that target various Herpesviridae species. Regular immunization with available vaccines has demonstrated a significant impact on lowering the incidence of HZ and PHN in people over 60 years of age. This article reviews the etiology, epidemiology, pathophysiology, clinical features, evaluation, and available treatments and vaccines for the management of HZ infection, using articles and reviews available in public databases to date (PubMed, Scopus, Embase, and manual searches of Google Scholar). In addition, the differences in safety and effectiveness between the antivirals that are currently licensed for the treatment of HZ, the potential use of novel antivirals in the future for treating HZ, and the antivirals' therapeutic or preventive effects on ZAP or PHN are also discussed.

Introduction: Photodynamic therapy (PDT) is increasingly recognized worldwide as a major therapeutic modality for the management of cancer and infectious diseases. The success of PDT largely depends on the design and performance of photosensitizers (PSs) capable of generating reactive oxygen species (ROS) upon light activation. However, traditional PSs face challenges such as poor solubility, limited tissue penetration, non-specific accumulation, and phototoxicity. The objective of this study is to provide an updated synthesis of advancements in this evolving field; therefore, a narrative review was conducted.

Methods: An extensive literature search was conducted using electronic databases including PubMed, Scopus, Web of Science, and Google Scholar up to March 2024. Keywords such as "photodynamic therapy", "photosensitizers", "nanoparticles", "ROS", and "theranostics" were used to identify relevant literature, with emphasis on original research articles, reviews, and clinical studies.

Results: This review highlights the evolution of photosensitizer systems, encompassing both natural and synthetic derivatives, and discusses how nanoparticle (NP)-based strategies such as up-conversion nanoparticles (UCNPs), lipid-based carriers, and polymeric systems have enhanced the therapeutic selectivity, ROS production, and tissue targeting of PDT. Particular attention is given to theranostic applications, combining imaging and therapy within a single platform. Furthermore, emerging clinical trials investigating PDT applications in cutaneous T-cell lymphoma, pancreatic cancer, systemic sclerosis, and head and neck cancers are summarized, illustrating the expanding translational potential of these technologies.

Discussion: These advances show a clear transition from a localized cytotoxic modality in PDT towards a precision nanomedicine modality. Using multifunctional nanocarriers in combination with optimized photosensitizers improves treatment efficacy and reduces off-target damage. Real-time monitoring of treatment and personalization is also made possible by the emergence of theranostic platforms. Collectively, current clinical studies indicate that PDT will be an increasingly flexible and translational approach across diverse disease settings.

Conclusion: This review paper focuses on PDT with different classes of PSs, with a particular emphasis on nano-based applications at both therapeutic and diagnostic levels.

Introduction: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by hormonal imbalances, ovarian dysfunction, and metabolic irregularities. Jiawei Zaoqi Decoction (JWZQD), a Traditional Chinese Medicine (TCM) formulation, has shown potential as a multi-targeted therapeutic intervention for PCOS. However, its underlying mechanisms remain unclear. In this study, we explored the therapeutic effects and molecular mechanisms of JWZQD in managing PCOS.

Methods: We employed a multi-model approach integrating clinical data, animal models, and mechanistic assays. Clinical efficacy was evaluated in a cohort of PCOS patients, while a letrozole- induced rat model combined with a high-fat diet was used to assess reproductive and metabolic outcomes. Network pharmacology, Gene Ontology, KEGG enrichment, and protein-protein interaction analyses were applied to identify key targets and pathways. Granulosa-cell experiments under oxidative stress and insulin stimulation were performed for functional validation.

Results: JWZQD administration significantly decreased serum luteinizing hormone and testosterone levels, improved insulin, and restored estrous cyclicity in PCOS patients and rats. Histology and ultrasound revealed reduced cystic follicles and normalized ovarian stroma. Bioinformatic analyses identified cellular senescence and AGE-RAGE signaling as core pathways, with quercetin and fisetin emerging as critical bioactive compounds. In vitro, quercetin and fisetin suppressed senescence markers (p21, p53, γH2AX) and rescued granulosa-cell proliferative capacity, confirming the network predictions.

Discussion: These findings provide mechanistic insight into how JWZQD ameliorates PCOS, highlighting its multi-targeted regulation of endocrine, metabolic, and ovarian functions. Importantly, our results suggest that targeting granulosa-cell senescence may represent a novel therapeutic strategy.

Conclusion: JWZQD mitigates PCOS by modulating AGE-RAGE-mediated granulosa-cell senescence through its active compounds quercetin and fisetin. This study supports the clinical potential of JWZQD as an alternative or complementary therapy for PCOS.

Introduction: Delayed-onset diarrhea, a common adverse reaction to irinotecan, affects both the effectiveness of chemotherapy and the quality of life of cancer patients. This type of diarrhea has been effectively treated with Shengjiang Xiexin decoction (SXD), a staple in traditional Chinese medicine (TCM). This study sought to clarify the pharmacological mechanism by which SXD alleviates irinotecan-induced diarrhea.

Methods: Irinotecan-triggered delayed-onset diarrhea was modeled in rats, and effectiveness was investigated by evaluating body weight, diarrhea score, and intestinal mucosal pathology. The research investigated tight junction protein expressions in intestinal epithelial cells (IECs), especially Zonula occludens-1 (ZO-1) and occludin, by immunofluorescence (IF) labeling. Furthermore, intestinal permeability was evaluated utilizing the fluorescence-labeled isothiocyanate (FITC) glucan technique. Intestinal short-chain fatty acids (SCFAs) were quantified by use of ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), and colorimetric analysis was utilized to assess β-glucuronidase activity in the gut. Finally, the mRNA expressions of TLR4-Myd88-JNK/NF-κB and Muc2 in the gut were quantified by use of reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR).

Results: SXD had considerable protective benefits in rats, alleviating body weight loss, decreasing diarrhea scores, and diminishing intestinal mucosal damage and permeability. The therapy increased the expression of ZO-1 and occludin proteins, therefore preserving the integrity of the intestinal mucosal barrier. Moreover, SXD significantly elevated SCFA levels in the gut while reducing β-glucuronidase activity. SXD reduced the mRNA levels of JNK, NF-κB, Myd88, and TLR4, while increasing those of Muc2 in rat jejunum tissues.

Discussion: SXD ameliorates irinotecan-induced diarrhea via a multi-mechanism approach, including inhibition of bacterial β-glucuronidase, restoration of beneficial short-chain fatty acids, enhancement of intestinal barrier integrity, and suppression of the TLR4/MyD88/NF-κB inflammatory pathway.

Conclusion: This study provides a foundation for further investigation of SXD as a complementary strategy to improve the safety of irinotecan chemotherapy.

Tenoxicam is a non-steroidal anti-inflammatory drug. Official compendia report Tenoxicam analysis by titration, while the literature reports analyses by High Performance Liquid Chromatography and Ultraviolet- Visible Spectrophotometry. Each method has its own characteristics, as do each active ingredient, and the analysis objective is also important, as is the matrix in which it is used. The combination of these factors and analytical awareness can result in a harmful, time-consuming, and costly process or a green, fast, and economical one. This work aims to evaluate the greenness of analytical methods for the analysis of Tenoxicam in a pharmaceutical matrix, using the National Environmental Methods Index, Eco-Scale Assessment, Green Analytical Procedure Index, and Blue Applicability Grade Index. The articles and monographs were selected from 2016 to 2025 from the main databases PubMed and ScienceDirect, as well as the British Pharmacopoeia. An overview of the analytical methods of the last 10 years for quantitative evaluation of Tenoxicam in pharmaceutical matrices showed that High Performance Liquid Chromatography is the most used method, methanol is the most used solvent, approximately 70% of the analyzes use toxic, hazardous and bioaccumulative reagents, average Eco-Scale Assessment of 82%, predominantly yellow Green Analytical Procedure Index and average Blue Applicability Grade Index of 66.7. There is still room to develop more environmentally friendly analytical conditions, and the combined use of green tools can guide choices and decision- making.

Background: Environmental exposure to volatile organic compounds (VOCs) may adversely affect liver function, particularly in adolescents; however, the evidence remains scarce.

Objective: This study aimed to evaluate the individual and combined effects of VOCs exposure on liver function in adolescents, as well as the potential mediating role of lactate dehydrogenase (LDH) and possible intervention strategies.

Methods: In total, 1,280 adolescents aged 12-19 years from the National Health and Nutrition Examination Survey were studied to examine the associations between 15 VOC metabolites and 4 liver function indicators. Four statistical models were employed to assess the associations, including weighted linear regression, restricted cubic splines, weighted quantile sum (WQS), and Bayesian kernel machine regression (BKMR). Mediation analysis was performed to evaluate whether LDH mediated or partially explained these associations.

Results: Among the 15 individual VOC metabolites, 8 were observed to have a significant association with specific liver function indicators. The WQS and BKMR models consistently identified significant associations between VOC mixtures and elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Additionally, AMCC [parent VOC (pVOC): N, N-dimethylformamide] and HMPMA (pVOC: crotonaldehyde) were identified as major contributors to the combined effect. Mediation analysis showed the potential mediation effect of serum LDH on these associations. Moreover, the adverse effect of VOC exposure on adolescent liver function was significantly mitigated with adequate vitamin D intake.

Discussion: The results indicate that VOC exposure is positively associated with elevated liver function indicators in adolescents, with AMCC and HMPMA as main contributors. The mediating role of LDH suggests that oxidative stress may serve as a key mechanistic pathway underlying VOC-induced liver injury. Additionally, adequate vitamin D intake appears to mitigate these adverse effects.

Conclusion: Our findings revealed a positive association between exposure to VOC and liver function in adolescents, and suggest that LDH may be a potential mechanism for VOC-induced liver injury. Supplementing with vitamin D may help protect adolescent liver function from the effects of VOC exposure.

Researchers are in a continual quest for advanced nanotechnology-based delivery systems to revolutionize the field of brain targeting. Nanotechnology has special significance for drug candidates failing therapeutically due to their low solubility, permeability, and stability in different physiological environments. They provide the right platform for the enhancement of the bioavailability of drug molecules via controlled release and proper targeting. Recently, quantum dots, the nanoparticles composed of fluorescent semiconducting materials, are gaining much popularity among researchers because of their promising multipronged approach due to numerous unique characteristics such as high surface area owing to their nanosize, fluorescence intensity, photoluminescence, optical and electrical properties, targeting capabilities, high quantum yield, high drug encapsulation efficiencies, high biological membrane permeability capacities, and photostability. Quantum dots possess immense potential for targeting drugs and diagnostic molecules to the site of interest by permeating the blood-brain barrier (BBB), which is the main obstacle for brain delivery. Furthermore, the effectiveness of this nanosystem increases manyfold as compared to its existing counterparts due to its multifunctional approaches of maximizing drug targeting, imaging, and diagnosis to fulfill the purpose of BBB permeation, visualizing brain structures, and monitoring drug delivery patterns for effective treatment of brain disorders. This review focuses on the discussion of the blood-brain barrier as a major obstacle, quantum dots as emerging tools for imaging and targeting, and their recent developments with a special emphasis on toxicity aspects, their biodistribution, challenges, and future prospects.