Current Pharmaceutical Design[JOURNAL]
Sun
200 papers
Rheumatoid Arthritis: A Comprehensive Review of Etiology, Pathophysiology, and Innovative Therapeutic Advancements.
Karabhari A, Rathee S, Soni S … +1 more , Patil UK
Curr Pharm Des · 2026 May · PMID 42136488 · Publisher ↗
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, cartilage degradation, and bone erosion, ultimately leading to joint deformities and functional impairment. Aff...
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, cartilage degradation, and bone erosion, ultimately leading to joint deformities and functional impairment. Affecting approximately 1% of the global population, RA imposes a significant burden on healthcare systems and patient quality of life. The disease pathogenesis involves a complex interplay between genetic predisposition, environmental triggers, and dysregulated immune responses. While genome-wide association studies (GWAS) have identified multiple susceptibility loci, genetic factors alone do not fully account for disease onset. Environmental influences, such as smoking, obesity, and microbial dysbiosis, contribute to immune tolerance breakdown, leading to aberrant activation of T cells, B cells, and proinflammatory cytokines, including TNF-α and IL-6. Conventional therapies, including disease-modifying antirheumatic drugs (DMARDs) and biologics, have significantly improved disease outcomes but remain limited by non-responsiveness in a subset of patients and long-term safety concerns. Recent advances in nanotechnology, biomimetic drug carriers, and precision medicine offer promising avenues for overcoming these challenges. Innovative therapeutic approaches, such as in situ hydrogels targeting neutrophil extracellular traps (NETs), liposomal drug delivery systems enhancing bioavailability, and nanoparticle-based immune modulation, provide new hope for improving treatment efficacy and reducing systemic side effects. This review comprehensively explores RA's multifactorial etiology, immunopathogenesis, and emerging therapeutic strategies, highlighting novel drug delivery systems and personalized treatment approaches that may revolutionize RA management.
Polypill Therapy is the Key to Improving Treatment Adherence in Comorbid Patients with High Cardiovascular Risk: A Systematic Review and Meta-Analysis.
Garanin A, Aydumova O, Rubanenko A
Curr Pharm Des · 2026 May · PMID 42136487 · Publisher ↗
INTRODUCTION: The creation of a fixed combination ("polypill") primarily reflects the medical community's efforts to increase patient adherence to treatment, which contributes to both individual and population- level ris...
INTRODUCTION: The creation of a fixed combination ("polypill") primarily reflects the medical community's efforts to increase patient adherence to treatment, which contributes to both individual and population- level risk reduction. However, different studies use various methods to assess patient adherence. The results of different studies regarding this topic are controversial. Some studies demonstrate positive effects of "polypill" administration on patient adherence, and other studies show no statistically significant differences compared to standard therapy. The aim of this review was to assess the adherence to treatment in comorbid patients with high cardiovascular risk who used "polypill" therapy compared to standard monocomponent therapy. METHODS: The search was conducted in accordance with PRISMA requirements across the databases PubMed, Google Scholar, and ClinicalTrials.gov. Two independent reviewers conducted the search, and in cases of disagreement, a third reviewer was involved. A total of 1.941 publications were analyzed, of which 358 were found in PubMed, 1.580 were found in Google Scholar, and 3 were found in Clinical Trials. A total of 11 publications were selected for the final analysis of full-text articles. The meta-analysis evaluated the adherence to therapy in patients after myocardial infarction, with dyslipidemia, arterial hypertension, and high cardiovascular risk, who used "polypill" therapy, compared to standard therapy with monocomponent drugs. RESULTS: The meta-analysis of adherence to "polypill" therapy compared to standard therapy included 11 studies involving comorbid patients with high cardiovascular risk. The total number of patients was 39.286. 19.664 patients used "polypill" therapy, and 19.622 patients used standard therapy with monocomponent drugs. According to the results of the meta-analysis, high adherence to treatment is more common in patients using "polypill" compared to standard therapy (relative risk (RR) 1.434 (95% CI 1.26-1.64, p<0.001). DISCUSSION: "Polypill" therapy is generally effective in increasing adherence. Attention should also be paid to other factors that can influence patients' adherence to "polypill" therapy, such as the duration of the follow-up period, the number of patient visits, initial adherence, and patient education. The advantages and limitations of "polypill" therapy are described in this review. Despite certain limitations, "polypill" is considered a promising option for improving patients' adherence in clinical practice, especially when combined with other adherence- enhancing strategies. CONCLUSION: A current systematic review and meta-analysis have shown that the use of fixed-dose combinations ("polypill") in comorbid patients with high cardiovascular risk is associated with greater adherence to treatment compared to standard therapy with monocomponent drugs.
Yinzhilan Formula Ameliorates Healing Delay in Diabetic Ulcer by Inhibiting PARP1 Activation and Regulating Macrophage Polarization.
Feng J, Ni Y, Zhang W … +6 more , Tang M, Wang S, Sun J, Han X, Zhou M, Zhao C
Curr Pharm Des · 2026 May · PMID 42099170 · Publisher ↗
INTRODUCTION: Yinzhilan formula (YZL) is an effective prescription for diabetic ulcers (DU) with clinical efficacy. This study aimed to explore the mechanism of YZL in ameliorating the healing delay of DU through network...
INTRODUCTION: Yinzhilan formula (YZL) is an effective prescription for diabetic ulcers (DU) with clinical efficacy. This study aimed to explore the mechanism of YZL in ameliorating the healing delay of DU through network pharmacology and experimental validation. METHODS: Network pharmacology integrated with bioinformatics to screen the chemical composition of YZL, as well as its protein targets and disease targets. A mouse model of DU was established, and the efficacy of YZL was evaluated according to ulcer size and histopathological examination. The levels of inflammatory factors were detected by ELISA, and the changes in macrophage polarization were detected by immunofluorescence and flow cytometry. RESULTS: Network pharmacology identified 291 potential targets in YZL, which synergistically targeted PARP1 and STAT3 to exert their role in promoting wound healing. In vivo experiments showed that YZL accelerated wound closure, regulated the levels of inflammatory factors and macrophage polarization, and suppressed the mRNA and protein expression levels of PARP1 and STAT3. DISCUSSION: Bioinformatics studies suggested that HSP90AA1, IL6, PARP1, and STAT3 may be potential targets of YZL in the treatment of DU. Immune infiltration analysis suggested that macrophages may be related to the mechanism of action. CONCLUSION: YZL may accelerate DU healing by inhibiting PARP1 and STAT3 and reprogramming macrophage polarization towards the M2 phenotype.
Artificial Intelligence in Non-Alcoholic Fatty Liver Disease and Fibrosis: A Narrative Review.
Bakhshi A, Akbari M, Maleki F … +7 more , Fiuji H, Fathi A, Gataa IS, Rajabian M, Gharib M, Naderi SH, Avan A
Curr Pharm Des · 2026 Apr · PMID 42083947 · Publisher ↗
Non-Alcoholic Fatty Liver Disease (NAFLD) is a prevalent chronic liver condition that can progress to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. While liver biopsy remains the gold...
Non-Alcoholic Fatty Liver Disease (NAFLD) is a prevalent chronic liver condition that can progress to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. While liver biopsy remains the gold standard for diagnosis, its invasiveness and cost limit its routine use. Recent advances in Artificial Intelligence (AI), particularly machine learning and deep learning, have created opportunities for accurate, non-invasive, and scalable assessment of NAFLD and related fibrosis. This narrative review summarizes recent studies applying image-based AI techniques, including convolutional and recurrent neural networks, as well as multimodal models combining imaging and clinical data. These approaches enhance the detection and grading of hepatic steatosis and fibrosis, improve diagnostic accuracy compared with conventional imaging or scoring systems, and enable standardized, cost-effective workflows using widely available modalities such as ultrasound and magnetic resonance imaging. Challenges remain, including the need for large, well-annotated datasets, interpretability of deep learning models, and mitigation of algorithmic bias. Despite these limitations, AI-assisted imaging holds substantial promise for earlier diagnosis, risk stratification, and personalized patient monitoring for NAFLD. Successful translation into clinical practice will require multidisciplinary collaboration, robust validation across diverse populations, and careful attention to ethical considerations such as data privacy and fairness that ultimately support improved patient outcomes and more efficient management of liver disease.
Revolutionizing Psoriasis Therapy: Cutting-Edge Nanocarrier Systems, Formulation Strategies, and Future Horizons.
Khare S, Vikal A, Maurya R … +5 more , Singh N, Singh C, Patel P, Gupta GD, Kurmi BD
Curr Pharm Des · 2026 Apr · PMID 42083545 · Publisher ↗
Psoriasis is a chronic autoimmune skin disease characterized by hyperproliferation of keratinocytes and excessive inflammation, resulting in erythema, scaling, and thickening of the epidermis. Traditional topical and sys...
Psoriasis is a chronic autoimmune skin disease characterized by hyperproliferation of keratinocytes and excessive inflammation, resulting in erythema, scaling, and thickening of the epidermis. Traditional topical and systemic therapies are limited by inadequate skin penetration, systemic toxicity, and poor drug bioavailability. Over the past decade, nanocarrier-based drug delivery systems, such as liposomes, solid lipid nanoparticles (SLNs), polymeric nanoparticles (PNPs), and ethosomes, have emerged as promising approaches to overcome these challenges. These nanocarriers enhance drug stability, prolong release, and enable targeted delivery to psoriatic lesions, thereby improving therapeutic efficacy while minimizing side effects. This review highlights recent progress in nanocarrier-based formulations for treating psoriasis, with emphasis on their mechanistic advantages, formulation strategies, and therapeutic outcomes. Liposomes and ethosomes promote drug permeation across the skin, whereas SLNs and PNPs offer improved drug retention and controlled release. Recent studies demonstrate that nanocarriers can efficiently encapsulate corticosteroids, immunomodulators, and anti-inflammatory agents, leading to better clinical results. Despite these advancements, challenges, such as low drug-loading capacity, stability issues, and difficulties in large-scale production, remain. Future research should focus on stimulus-responsive nanocarriers, surface-functionalized delivery systems, and AI-based optimization to advance precision medicine strategies. With ongoing innovation, nanotechnology holds significant potential to transform psoriasis management by enabling safer, more effective, and patient-friendly treatments.
Polysaccharide-Based Nanocarriers: Innovative Platforms for Enhanced Vaccine Delivery and Improved Immune Response Stimulation.
Chauhan A, Sharma R, Sharma R … +5 more , Kumar M, Singh TG, Alsaidan OA, Alzarea SI, Awasthi A
Curr Pharm Des · 2026 Apr · PMID 42083544 · Publisher ↗
This review highlights the emerging role of polysaccharide-based nanocarriers in enhancing vaccine delivery and immune responses. It examines how these nanocarriers address key challenges in vaccine development, includin...
This review highlights the emerging role of polysaccharide-based nanocarriers in enhancing vaccine delivery and immune responses. It examines how these nanocarriers address key challenges in vaccine development, including antigen instability and suboptimal immune activation. Polysaccharide nanocarriers offer distinct advantages: improved antigen stability, controlled release, targeted delivery, stimulation of both humoral and cellular immunity, and excellent biocompatibility and biodegradability. Various types are discussed, such as chitosan and its derivatives (carboxylated and quaternized), mannose-based, glucan-based, and inulin-based adjuvants. The review also explores polysaccharides from Chinese medicinal herbs-like lentinan, astragalus, and angelica polysaccharides, for their adjuvant and delivery properties. Case studies demonstrate how these systems enhance immune responses across different vaccines. The authors suggest that polysaccharide nanocarriers could enable next-generation vaccination strategies that are more effective, stable, and safer than current adjuvants. However, they stress the need for further optimization, mechanistic understanding, and clinical validation before widespread adoption. In conclusion, polysaccharide nanocarriers show great promise as innovative platforms for vaccine delivery and immunomodulation, but additional research is essential to fully realize their potential in clinical settings.
From Liposomes to Leapfrogs: The New Era of Anthracycline Nanocarriers.
Tasqeeruddin S, Annamalai DA, Sanghvi G … +6 more , Sinha A, Roopashree R, Shankhyan A, Mishra S, Abosaoda MK, Joshi KK
Curr Pharm Des · 2026 Apr · PMID 42083543 · Publisher ↗
Anthracyclines are potent therapeutic agents widely used in cancer treatment and other medical applications, including infectious diseases and inflammatory disorders. However, their clinical utility is often restricted b...
Anthracyclines are potent therapeutic agents widely used in cancer treatment and other medical applications, including infectious diseases and inflammatory disorders. However, their clinical utility is often restricted by severe systemic toxicity, poor biodistribution, and the emergence of multidrug resistance (MDR). To address these limitations, nanocarrier-based drug delivery systems have been developed to improve therapeutic selectivity and safety. Among them, liposomal formulations have achieved the highest level of clinical translation. FDA-approved liposomal anthracyclines such as Doxil® (doxorubicin), DaunoXome® (daunorubicin), and Vyxeos® (daunorubicin-cytarabine) have demonstrated enhanced pharmacokinetics, reduced cardiotoxicity, and improved therapeutic outcomes compared with conventional formulations. Beyond liposomes, alternative and emerging nanocarriers, including polymeric nanoparticles, micellar systems, dendrimeric carriers, and hybrid lipid-polymer constructs, are being explored to achieve higher drug loading, controlled release, and targeted tissue penetration. These formulations also show promise for antimicrobial and immunomodulatory therapies. Nevertheless, key challenges such as safety concerns, large-scale production, and regulatory barriers continue to impede broad clinical adoption. This review provides a comprehensive overview of liposomal and alternative nanoformulations for anthracyclines, discussing their advantages, limitations, and clinical potential while addressing the key challenges that must be overcome for their successful translation into widespread medical use, while also highlighting emerging biohybrid, extracellular vesicle-based, and stimuli-responsive systems that represent leapfrogging innovations in anthracycline delivery.
Nanomedicine-Based Approaches for Therapeutic Delivery Across the Blood-Brain Barrier in Neurological Disorders.
Garg A, Lavania K, Parhi R … +3 more , Singh GK, Ahmad J, Jain A
Curr Pharm Des · 2026 Apr · PMID 42083542 · Publisher ↗
Therapeutic delivery to the Central Nervous System (CNS) is challenging for formulation scientists due to the transfer of therapeutics across the Blood-Brain Barrier (BBB). The BBB consists of a selective semi-permeable...
Therapeutic delivery to the Central Nervous System (CNS) is challenging for formulation scientists due to the transfer of therapeutics across the Blood-Brain Barrier (BBB). The BBB consists of a selective semi-permeable anatomical structure of the capillary basement membrane, capillary endothelial cells, pericytes, and astrocytes. It restricts the drug transfer from the blood compartment to the brain tissues. Therefore, the desirable effects of various therapeutics in different CNS disorders (like Alzheimer's disease, schizophrenia, Parkinson's disease, etc.) require the transfer of drugs across the BBB. Hence, various approaches have been explored for deeper penetration of CNS-acting drugs across the BBB. Among various formulation approaches, Drug Delivery Systems (DDS) utilizing colloidal carrier systems are one of the most promising strategies to overcome BBB limitations and achieve brain targeting in different CNS disorders. This review provides a comprehensive discussion of drug delivery challenges across the BBB and technology advancements utilized to achieve improved therapeutic efficacy in different CNS disorders.
Diosgenin Alleviates Inflammation in the Colon and Hippocampus and Partly Attenuates Comorbid Autistic-like Behaviors in Experimental Colitis in Mice.
Arami A, Lorigooini Z, Ghaderi H … +3 more , Noori A, Anjomshoa M, Amini-Khoei H
Curr Pharm Des · 2026 Apr · PMID 42083409 · Publisher ↗
INTRODUCTION: Inflammatory bowel disease (IBD) is comorbid with behavioral disorders like autism spectrum disorder (ASD). Neuroinflammation is involved in the pathophysiology of ASD. Diosgenin has pharmacological propert...
INTRODUCTION: Inflammatory bowel disease (IBD) is comorbid with behavioral disorders like autism spectrum disorder (ASD). Neuroinflammation is involved in the pathophysiology of ASD. Diosgenin has pharmacological properties. We aimed to assess the potential properties of diosgenin in mitigating comorbid autistic-like behaviors with colitis in mice, focusing on its probable effects on the neuroinflammatory response in the hippocampus. METHODS: Colitis was induced using acetic acid. Forty male mice were divided into five groups and treated intraperitoneally for seven continuous days with 0.9% saline containing Tween 20 at a concentration of 2% (10 ml/kg) or diosgenin (25, 50, and 100 mg/ kg). Behavioral tests, including sociability and social preference indexes, passive avoidance memory, and aggressive-like behaviors, were assessed. Then, the colon and hippocampus were dissected out. A microscopic evaluation of the colon was done. RT-PCR measured TLR4, TNF-α, IL-1β, and NLRP3 gene expression in the hippocampus and colon. RESULTS: Colitis is associated with histopathological alterations in the colon and an increase in the gene expression of inflammatory mediators in the colon. Colitis reduced sociability and social preference indexes, impaired passive avoidance memory, and increased aggressive-like behaviors. These behaviors are accompanied by increased gene expression of inflammatory mediators in the hippocampus. Diosgenin mitigated the negative effects of colitis on the hippocampus and colon. DISCUSSION: Diosgenin attenuated inflammatory responses in the colon, autistic-like behaviors, and expression of genes relevant to neuroinflammation in the hippocampus following colitis. CONCLUSION: Diosgenin likely alleviated autistic-like behaviors following colitis, possibly through the reduction of inflammatory gene expressions in the hippocampus.
Recent Advances in 6D Printing and Future Prospects for Biomedical Applications.
Sarkar A, Ranjan R, Chhabra R … +1 more , Pal RR
Curr Pharm Des · 2026 Apr · PMID 42083343 · Publisher ↗
A significant advancement in additive manufacturing, the switch from 3D to 6D printing opens up new avenues for biomedical innovation. Traditional 3D printing makes simple models, but it cannot precisely create very comp...
A significant advancement in additive manufacturing, the switch from 3D to 6D printing opens up new avenues for biomedical innovation. Traditional 3D printing makes simple models, but it cannot precisely create very complicated shapes that are needed for advanced medical devices. Even if later developments, such as 5D printing with multi-axis fabrication and 4D printing with stimulus-responsive materials, have increased structural strength and design flexibility, they are still unable to produce completely autonomous, patient- responsive systems. Multi-axis construction and intelligent, reprogrammable materials that can sense, react, and adjust to physiological stimuli like pH, temperature, enzymes, and mechanical stresses are novelly combined in 6D printing. Owing to its special capabilities, positioned as a game-changing technology for next-generation biomedical devices, enabling dynamic drug delivery platforms, adaptive prosthetics, and selfhealing orthopedic systems that exceed previous manufacturing techniques. With limitations such as a lack of multi-responsive materials, difficulties in producing it on a large scale, and complicated regulations, it is prevented from being widely used. This article explores novel applications of 6D printing, along with its technological merits over 3D-5D methods, and provides insights towards the development of bio-hybrid, effective, and clinically relevant outcomes in the biomedical field, including regenerative medicine and tissue engineering.
Review on the Potential Anti-aging Effects of Gastrodia elata.
Wang R, Xin C, Liu W … +3 more , Cheng Z, Zhu H, Han J
Curr Pharm Des · 2026 Apr · PMID 42059229 · Publisher ↗
Gastrodia elata Blume (G. elata) is a valuable traditional Chinese medicine (TCM) that has been widely used in China. We systematically reviewed tonic and life-extending records in ancient medical literature, as well as...
Gastrodia elata Blume (G. elata) is a valuable traditional Chinese medicine (TCM) that has been widely used in China. We systematically reviewed tonic and life-extending records in ancient medical literature, as well as the life-prolonging and senescence-delaying effects identified in modern pharmacological research, to provide a theoretical basis for the clinical application and product development of G. elata in tonification and anti-aging. Scientific databases, including CNKI (Chinese literature) and PubMed, were searched to gather relevant literature on the anti-aging effects of G. elata. The targets of the main chemical components of G. elata were predicted and collected through a database, and the intersection of compound targets and disease targets was identified. Protein-protein interaction network analysis, Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore the potential mechanisms underlying the anti-aging effects of G. elata. The record of G. elata demonstrates a definitive life-extending effect. Modern pharmacological studies have confirmed that it prolongs the lifespan of short-lived animals and slows the aging processes of the brain, skin, bone, and skeletal muscle in animals. Network pharmacology analysis identified 15 common targets shared between candidate target genes of G. elata and anti-aging target genes. TP53, ESR1, EP300, SIRT1, STAT3, CCND1, HDAC2, MDM2, PPARG, TNF, and HSP90AA1 were identified as core genes in the protein-protein interaction (PPI) network analysis. KEGG enrichment analysis indicated that the anti-aging mechanisms of G. elata may be associated with chemical receptor activation, insulin resistance, the citric acid cycle, the PPAR signaling pathway, the glucagon signaling pathway, and the thyroid hormone signaling pathway. This article summarizes previous studies and modern research on the anti-aging effects of G. elata, suggesting that it holds significant potential for clinical applications in anti-aging.
A Nanophytomedicine Approach Including Tea Tree Essential Oil for Possible Dental Applications: In vitro and In silico Evaluations.
Budama-Kilinc Y, Cakmakci N, Kecel-Gunduz S … +5 more , Suyabatmaz Ş, Alpay-Karaoglu S, Yilmaz-Atali P, Yapar EA, Kartal M
Curr Pharm Des · 2026 Apr · PMID 42059228 · Publisher ↗
INTRODUCTION: Tea tree essential oil (TTO) incorporated polylactic-co-glycolic acid (PLGA) nanoparticulate powder form was aimed to desined that can be applied with water and is effective against oral pathogens to preven...
INTRODUCTION: Tea tree essential oil (TTO) incorporated polylactic-co-glycolic acid (PLGA) nanoparticulate powder form was aimed to desined that can be applied with water and is effective against oral pathogens to prevent caries, and that is able to provide a long-lasting oral antiseptic effect. METHODS: TTO-PLGA nanoparticles (TTO-NPs) was synthesized by single emulsion technique; average particle size, PdI value and zeta potential was measured by Zetasizer; TTO-PLGA interactions were investigated by FTIR, and morphological analysis was performed by TEM analysis. Phytoactive release and performans tests were carried out with in vitro dissolution and DNA binding-cleavage tests while antimicrobial performance was investigated by Ames-Salmonella assay, susceptibility test, in silico Molecular Docking and Molecular Dynamics studies. RESULTS: TTO-NPs had an average particle size of 221.6 nm, a PdI of 0.103, and a zeta potential of -5.22 mV, 59.25% encapsulation efficiency and 25.65%. loading capacity. At the end of 5 h and 72 h the TTO release was 33.34±2.17% and 97.61±3.91% respectively. TTO-NPs were not mutagenic and were effective on investigated four cariogenic bacteria. The binding interactions of terpinen-4-ol, the main component of TTO, with Streptococcus mutans and Lactobacillus casei were revealed with enzyme-active-site-key residues. DISCUSSION: In vitro and in silico studies confirmed that TTO-NPs were non-mutagenic and exhibited strong antimicrobial activity against dental caries-causing bacteria like Streptococcus mutans and Lactobacillus casei. CONCLUSION: In conclusion, TTO-NPs, which can be used as a mouthwash or powder, represent a promising solution for reducing oral pathogens, meriting further in vivo and clinical evaluations.
Qishen Yiqi Formula Mitigates Heart Failure by Restoring Myocardial Energy Metabolism via AMPK: Insights from Multi-Omics Analysis.
Wang Y, Nie T, Chen X … +6 more , He X, Li L, Wang X, Huang Y, Fan G, Ni J
Curr Pharm Des · 2026 Apr · PMID 42059227 · Publisher ↗
INTRODUCTION: Heart failure (HF), a life-threatening syndrome with complex pathogenesis, is closely linked to myocardial metabolic remodeling, the critical driver of cardiac dysfunction. Optimizing myocardial energy meta...
INTRODUCTION: Heart failure (HF), a life-threatening syndrome with complex pathogenesis, is closely linked to myocardial metabolic remodeling, the critical driver of cardiac dysfunction. Optimizing myocardial energy metabolism represents a promising therapeutic strategy. Qishenyiqi formula (QSYQ), a traditional Chinese herbal compound, demonstrates cardioprotective effects, but its mechanisms in modulating substrate utilization and metabolic remodeling in transverse aortic constriction (TAC)-induced HF remain unclear. OBJECTIVE: This study investigates the therapeutic potential and molecular mechanisms of QSYQ in TACinduced HF. METHODS: TAC-induced HF mice were treated with QSYQ (1170 or 585 mg/kg) or vehicle for four weeks. Cardiac function was assessed through echocardiography, hemodynamic measurements, histopathology, fibrosis analysis, and heart failure biomarkers (ANP and BNP). Mitochondrial ultrastructure was evaluated by transmission electron microscopy, while mitochondrial function was quantified by measuring ATP levels, reactive oxygen species, and membrane potential. Integrated proteomics and metabolomics analyses were performed to identify metabolic pathways, which were subsequently validated by molecular assays. RESULTS: QSYQ attenuated cardiac hypertrophy, fibrosis, and dysfunction in TAC mice, improving ejection fraction and hemodynamics. It restored mitochondrial integrity and function, evidenced by normalized ultrastructure, increased ATP synthesis, reduced ROS, and stabilized membrane potential. Multi-omics integration revealed QSYQ's regulation of myocardial glucose and fatty acid metabolism mediated through AMPK and downstream targets PPARα and PGC-1α. DISCUSSION: These findings position QSYQ as a promising therapeutic candidate that targets core metabolic disturbances in HF. CONCLUSION: QSYQ mitigates TAC-induced HF by improving mitochondrial bioenergetics and metabolic remodeling through the AMPK/PPARα/PGC-1α pathway, supporting its potential as a metabolic therapy for HF.
Evaluation of Anti-GRP78 Nanobody Effect on the Treatment of Dry Eye Syndrome in Mice Model.
Farnoosh G, Taheri RA, Aghamollaei H
Curr Pharm Des · 2026 Apr · PMID 42059226 · Publisher ↗
INTRODUCTION: This investigation was designed to assess the therapeutic efficacy of a novel anti- GRP78 nanobody in the treatment of dry eye syndrome (DES) in a murine model. The focus was on the nanobody's anti-inflamma...
INTRODUCTION: This investigation was designed to assess the therapeutic efficacy of a novel anti- GRP78 nanobody in the treatment of dry eye syndrome (DES) in a murine model. The focus was on the nanobody's anti-inflammatory properties and its ability to increase tear production. METHODS: Topical atropine sulfate was implemented to induce DES in BALB/c rodents. Subsequently, mice were administered betamethasone (as a positive control), the purified anti-GRP78 nanobody, or a vehicle. The Schirmer tear test, ELISA, and qRT-PCR were implemented to quantify corneal inflammatory cytokines (TNF-α, IL-1α, IL-1β, IL-6), as well as a histopathological examination. RESULTS: Treatment with the anti-GRP78 nanobody meaningfully improved tear production and reduced levels of key inflammatory cytokines in corneal tissues. Histopathological analysis demonstrated noticeably reduced corneal epithelial damage and inflammatory cell infiltration, with efficacy comparable to betamethasone. DISCUSSION: The findings proposed that targeting GRP78 effectively mitigates DES pathology, presumably by preventing the inflammatory cascade. The nanobody's effectiveness, comparable to a conventional corticosteroid, combined with its potential for enhanced tissue penetration and minimal immunogenicity, underscores its potential as an innovative biologic therapy. CONCLUSION: The anti-GRP78 nanobody shows a lot of promise as a treatment for DES because it increases tear production and lowers corneal inflammation. In this term, more research is needed to see how it can be used in the clinic.
Advances in Cell Membrane Biomimetic Nano-Delivery Systems for Brain Tumor Therapy.
Zhou W, Liu R, Dai W … +2 more , Guo L, Yu Y
Curr Pharm Des · 2026 Apr · PMID 42003190 · Publisher ↗
Based on the concept of "imitating nature," biomimetic nano-delivery systems (BNDS) for brain tumor therapy are designed to simulate or utilize endogenous biological materials as delivery carriers, such as hybrids of eng...
Based on the concept of "imitating nature," biomimetic nano-delivery systems (BNDS) for brain tumor therapy are designed to simulate or utilize endogenous biological materials as delivery carriers, such as hybrids of engineered cell membranes and exogenous nanocarriers. These systems not only retain the physical and chemical properties of nanomaterials-enabling responses to photothermal stimuli, enzymes, and pH- but also inherit the advantages of their source cells, including physiological barrier-transport capabilities, specific targeting of focal tissues, and immunomodulatory effects. This enables the delivery of small-molecule drugs, nucleic acids, or therapeutic proteins across the blood-brain barrier (BBB) or the blood-tumor barrier (BTB) to tumor tissue. This article provides a comprehensive review of the construction, targeting mechanisms, and research progress of cell membrane-based nano-delivery systems derived from erythrocytes, immune cells, tumor cells, stem cells, and platelet membranes, with particular emphasis on their potential applications in brain tumor therapy.
Unleashing the Potential of 6-Mercaptopurine: Microemulsion Innovations for Enhanced Oral Bioavailability and Therapeutic Impact.
Singh P
Curr Pharm Des · 2026 Apr · PMID 42003189 · Publisher ↗
INTRODUCTION: 6-Mercaptopurine (6-MP) is an anticancer agent that disrupts cancer cell growth, ultimately causing cell death. It is classified as a BCS Class II drug, indicating poor aqueous solubility and limited oral b...
INTRODUCTION: 6-Mercaptopurine (6-MP) is an anticancer agent that disrupts cancer cell growth, ultimately causing cell death. It is classified as a BCS Class II drug, indicating poor aqueous solubility and limited oral bioavailability. To reduce these problems, nanocarriers have been prepared, which are non-toxic, biodegradable, and biocompatible. METHODS: The 6-MP loaded microemulsion has been formulated and characterized for physicochemical characterization, morphology, drug content, and release study. The cell line studies were implemented on the MDA-MB-231 cell line for cell viability and cellular uptake analysis. RESULTS: The optimized formulation (ME4) exhibited a droplet size of 115.47 ± 1.53 nm, entrapment efficiency of >90%, and a stable physicochemical profile. It demonstrated sustained drug release and significantly higher cellular uptake with an IC50 value of 2.17 ± 0.21 μM, compared to 3.87 ± 0.11 μM for free 6-MP. Ex-vivo permeation studies showed 80% drug permeation within 120 minutes versus 42% for pure 6-MP. Invivo pharmacokinetics revealed a 1.79-fold increase in oral bioavailability compared to the marketed tablet. XO inhibition studies confirmed ME4's role in reducing presystemic metabolism, with 59.60 ± 2.25% inhibition at 200 μg/mL, comparable to the standard inhibitor allopurinol (73.42 ± 2.34%). DISCUSSION: The developed microemulsion successfully addresses the dual challenge of poor solubility and extensive first-pass metabolism of 6-MP, resulting in significantly enhanced bioavailability and anticancer activity. These findings highlight its potential for future clinical development as a novel oral delivery platform for cancer therapy. CONCLUSION: The results demonstrate the future potential of 6-MP as a successful nanotherapeutic agent for cancer treatment that is more effective and safer.
Interplay between ADP-Ribosylation and Androgen Receptor Function in Prostate Cancer.
Reddy GSVSR, Samanta K, Kar P
Curr Pharm Des · 2026 Apr · PMID 42003188 · Publisher ↗
Androgen receptor (AR) signalling is central to both normal prostate physiology and prostate cancer (PCa) progression. Its activity is tightly regulated by localization, transcriptional control, and post-translational mo...
Androgen receptor (AR) signalling is central to both normal prostate physiology and prostate cancer (PCa) progression. Its activity is tightly regulated by localization, transcriptional control, and post-translational modifications. Among these, poly (ADP-ribose) polymerase (PARP) mediated ADP-ribosylation has emerged as a key regulator. Multisite cysteine mono-ADP-ribosylation of AR by PARP7 modulates its function. Molecular recognition of ADP-ribosyl-cysteine by PARP9/DTX3L influences AR-driven gene expression. Importantly, defects in homologous recombination repair (HRR) genes have made PARP inhibitors (PARPi) an effective treatment for BRCA (Breast cancer susceptibility genes 1 and 2)-mutated metastatic castration-resistant prostate cancer (mCRPC). Clinical trials such as TALAPRO-2 show that combining PARPi with AR signalling inhibitors can be effective; however, their benefit in tumours without HRR mutations remains unclear. PARP enzymes regulate AR via MARylation and PARylation, with inhibitors such as Olaparib, which disrupts AR-PARP crosstalk. In this review, we present current knowledge on the interplay between ADP-ribosylation and AR signalling in prostate cancer, emphasizing the roles of distinct PARP enzymes in shaping AR activity and therapeutic response. Herein, we focus on the combined contributions of MARylation and PARylation to prostate tumorigenesis. We also discuss how this complex regulatory network may contribute to the development of advanced prostate cancer therapies in the future. This could improve PARP inhibitor and AR signalling inhibitor combinations and allow more patients to benefit from them.
Cubosomes as Versatile Multifunctional Lipid-Based Nanocarriers for Drug Delivery: A Comprehensive Review.
Tekade A, Shewale A, Shivakumar HN … +2 more , Shinde R, Nimbalkar J
Curr Pharm Des · 2026 Apr · PMID 42003187 · Publisher ↗
Cubosomes (QBS) are self-assembled, nanostructured lipid carriers characterized by a bicontinuous cubic liquid crystalline architecture with a three-dimensional honeycomb-like morphology. Their unique internal structure...
Cubosomes (QBS) are self-assembled, nanostructured lipid carriers characterized by a bicontinuous cubic liquid crystalline architecture with a three-dimensional honeycomb-like morphology. Their unique internal structure allows simultaneous encapsulation of hydrophilic, lipophilic, and amphiphilic compounds, enabling sustained, site-specific, and targeted drug delivery through various routes, including oral, ocular, nasal, transdermal, and vaginal administration. Composed primarily of amphiphilic lipids such as Glyceryl Monooleate (GMO) and stabilized with surfactants like Pluronic F-127, QBS exhibits superior biocompatibility, structural integrity, and long-term colloidal stability. QBS are typically fabricated using either top-down or bottom-up strategies. Top-down approaches such as high-pressure homogenization, probe sonication, and spray drying fragment bulk cubic phases into nanosized dispersions, ensuring scalability and uniformity. Conversely, bottom-up methods, including the hydrotrope technique, vortex dispersion, and solvent evaporation, enable spontaneous QBS formation under mild conditions ideal for thermolabile actives. Physicochemical properties depend on lipid-to-stabilizer ratios, solvent composition, and processing parameters. Characterization techniques such as Dynamic Light Scattering (DLS), Small-Angle X-ray Scattering (SAXS), Transmission Electron Microscopy (TEM), and Confocal Laser Scanning Microscopy (CLSM) confirm particle size, morphology, and internal nanostructure. Zeta potential and MTT assays evaluate stability and cytocompatibility, while in vitro and ex vivo studies assess drug entrapment, release, and permeation behaviour. QBS represent an advanced class of lyotropic liquid-crystalline nanocarriers with high drug-loading potential, excellent biocompatibility, and controlled-release performance. Their multifunctional versatility underscores their promise as next-generation platforms for targeted and sustained drug delivery applications.
Emerging Diagnostic Tools and Therapeutic Approaches for Liver Cirrhosis Management.
Mukherjee S, Kumar M, Das S … +5 more , Shafi S, Srivastava S, Mishra MK, Singh AK, Pal RR
Curr Pharm Des · 2026 Apr · PMID 42003186 · Publisher ↗
Liver cirrhosis, a chronic liver disease identified by the formation of regenerative nodules along with fibrous bands, poses significant challenges in diagnosis and treatment. In the world, the most common factors of cir...
Liver cirrhosis, a chronic liver disease identified by the formation of regenerative nodules along with fibrous bands, poses significant challenges in diagnosis and treatment. In the world, the most common factors of cirrhosis are Hepatitis C Virus (HCV), alcoholic liver disease, and Non-Alcoholic Steatohepatitis (NASH). The disease develops from a presymptomatic phase to a symptomatic phase, which often results in hospitalization, poor quality of life, and high mortality. The treatment of liver cirrhosis is centred on the treatment of the causes and complications, and liver transplantation is required in some cases. This mini-review explores innovative strategies in liver cirrhosis detection and intervention, highlighting recent advancements and future directions. Current diagnostic methods include physical examination and serologic tests detecting secondary indicators of liver dysfunction and fibrosis. Diagnostic tools encompass established biomarkers such as serum albumin, prothrombin time, bile acid levels, and platelet count, as well as AI-assisted diagnostic tools that use digital imaging and pathology data. Novel therapeutic approaches like antifibrotic agents, targeted therapies for specific etiologies, endoscopic interventions, and innovative stem cell-based therapies, particularly mesenchymal stem cells, offer promising approaches for liver regeneration and fibrosis reduction through their multidirectional differentiation potential and secretion of cytokines, growth factors, and matrix metalloproteinases. However, additional studies are required to enhance the effectiveness of these interventions. Future directions emphasize primary prevention, early fibrosis screening using non-invasive testing, and active targeting of fibrogenesis pathways. More clinical studies are essential to treat cirrhosis and improve patient outcomes.
Chebulinic Acid Exerts Anti-rotavirus Effects through the p38MAPK/ERK1/2 Signaling Pathway.
Yu J, Zhang D, Qian Y … +9 more , Ruan Y, Zhou Y, Jiang X, Liu F, Zhou J, Rong Z, He Z, Song L, Zhao W
Curr Pharm Des · 2026 Apr · PMID 42003185 · Publisher ↗
INTRODUCTION: Rotavirus (RV) is a leading cause of diarrhea in infants and young children. Drugs effective against RV infection are not yet available in clinical practice. To investigate the anti-RV activity of chebulini...
INTRODUCTION: Rotavirus (RV) is a leading cause of diarrhea in infants and young children. Drugs effective against RV infection are not yet available in clinical practice. To investigate the anti-RV activity of chebulinic acid (CA) and its potential mechanism against RV. METHODS: The anti-RV activity of CA in vitro was evaluated by CCK8 assay, and the effects of CA on VP6 expression for RV RNA synthesis and protein expression were assessed using qRT-PCR、western blotting, and immunofluorescence, respectively. Before mechanistic validation, an in silico network pharmacology screen was performed to build a CA-host target-interaction map; DAVID enrichment flagged the p38/ERK axis as a top hit. Additionally, immunofluorescence and DCFH-DA ROS fluorescent probe were used to assess CA's effects against RV-induced ROS production and its direct ROS-scavenging activity, respectively, and western blotting was employed to evaluate whether CA exerts anti-RV activity by inhibiting the p38MAPK/ERK1/2 signaling pathway. Furthermore, we also evaluated the anti-viral effect of CA in RVinfected 4 days post-fertilization (4dpf) zebrafish model. RESULTS: Our results indicated that 4-10 μmol/L of CA has the ability to hinder VP6 expression, and it also decreased mitochondrial ROS production. Network pharmacology screening had previously identified 38 CA- RV intersection targets and ranked the p38 MAPK axis as the top-enriched pathway. Further research confirmed that CA downregulated p38MAPK/ERK1/2 phosphorylation levels in response to viral infection. In the RV-infected zebrafish model, CA greatly improved the survival rate. In addition, RV infection resulted in abnormal behavior in zebrafish, and CA was found to substantially decrease the incidence of convulsive behavior. The intestinal tract of zebrafish treated with CA led to the restoration of intestinal morphology and exhibited fewer inflammatory cell infiltrates, with a significantly reduced degree of inflammation compared to the viral group. DISCUSSION: This study comprehensively evaluated the anti-RV activity of CA using two RV strains, RV-WA and SA-11, an infected-cell model in vitro, as well as the RV-WA-infected zebrafish model in vivo. As we know, CA, belonging to polyphenolic compounds, possesses notable antioxidant and anti-inflammatory potential; therefore, we investigated how RV-induced oxidative stress affected the host cell apoptosis and mitochondrial membrane potential, and how it activated the p38MAPK/ERK1/2 kinase signaling pathway. Our findings demonstrate that CA can reverse these pathological alterations and thereby exert anti-RV effects, offering a new therapeutic strategy against RV infection. CONCLUSION: This study first demonstrated that CA possessed anti-RV properties by inhibiting mitochondrial oxidation-induced apoptosis via the p38MAPK/ERK1/2 kinase signaling pathway. These findings provided a basis for the clinical application of CA as an anti-RV therapy.</p>.
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