Pharmaceutics最新文献

{"title":"Surface-Engineered Phytochemical Nanomedicines for Postmenopausal Osteoporosis: Skeletal Targeting, Imaging-Supported Evaluation, and Therapeutic Performance.","authors":"Hongwei Gao, Shaorong Li, Han Wu, Weijian Wang, Jianshi Song, Jiaqi Li, Xiuqi Shan, Wei Zhang","doi":"10.3390/pharmaceutics18091163","DOIUrl":"10.3390/pharmaceutics18091163","url":null,"abstract":"<p><p>Postmenopausal osteoporosis (PMOP) is a metabolic bone disease driven by estrogen deficiency and a major contributor to fragility fractures, yet long-term use of current antiresorptive and anabolic agents remains constrained by tolerability and adherence. Plant-derived bioactive compounds-including flavonoids, isoflavones, curcuminoids, and stilbenes-show bone-protective activity in ovariectomized (OVX) models but share common delivery barriers: poor aqueous solubility, low oral bioavailability, rapid metabolic clearance, and limited skeletal targeting. Conventional nanonization improves systemic pharmacokinetics but cannot by itself address the spatial heterogeneity of skeletal target sites. This review focuses on surface-engineered phytochemical nanomedicines, in which mineral-affinity, cell-affinity, and pathology-responsive modules are introduced at the carrier interface to enhance bone-associated distribution, local retention, and microenvironment-responsive release. Organized around nanocarrier platforms, it summarizes cross-platform surface/interfacial engineering strategies and discusses how whole-body, ex vivo, and bone-section imaging can be combined with quantitative exposure assessment, micro-computed tomography (micro-CT), bone turnover markers, and histology to characterize carrier- or probe-associated distribution, spatial localization, and therapeutic performance, respectively. It then considers translational issues, including formulation reproducibility, ligand-density effects, model relevance, and long-term safety. The review aims to provide a framework for surface-engineered phytochemical strategies and a reference approach for multimodal, imaging-based evaluation of therapeutic outcomes.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morin-Loaded PLGA-Chitosan Nanoparticles Attenuate PTZ-Induced Seizure-Related Behavioral, Biochemical, and Transcriptional Changes in Male Rats.","authors":"Ashraf Kakoo, Azad Hasan Kheder, Ali A Mohammedsaeed, Trefa Salih Mohamad, Mohammed Awat Ali, Mohammad B Ghayour, Arash Abdolmaleki, Dlzar B Rahman, Shang Ziyad Abdulqadir, Taban Kamal Rasheed, Mohammed Jarjees Hashm, Shukur Wasman Smail","doi":"10.3390/pharmaceutics18091170","DOIUrl":"10.3390/pharmaceutics18091170","url":null,"abstract":"<p><p><b>Aims:</b> Morin is a flavonoid with potential neuroprotective and anti-inflammatory properties. This study evaluated the anticonvulsant and anxiolytic effects of morin-loaded PLGA-chitosan nanoparticles (Morin-PLGA-CS NPs) in male Wistar rats. <b>Methods:</b> Morin-PLGA-CS NPs were synthesized using a modified single emulsion-solvent evaporation method followed by CS coating. NPs were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), and in vitro drug release analysis. Adult male Wistar rats received intraperitoneal injections of free morin (25 mg/kg), Morin-PLGA-CS NPs, diazepam (1 mg/kg), blank NPs, or vehicle. Behavioral assessments included the open-field test (OFT), elevated-plus maze (EPM), novel object recognition (NOR) test, and pentobarbital-induced sleep test. Anticonvulsant activity was evaluated using PTZ-induced seizure latency. Cytokine concentrations in cortical and hippocampal tissue lysates were quantified by ELISA at 12 h post-PTZ. Hippocampal relative mRNA expression of Nrf2, HO-1, GFAP, and Iba1 was quantified by quantitative real-time PCR (qRT-PCR). <b>Results:</b> Morin-PLGA-CS NPs demonstrated a hydrodynamic diameter of 221.6 nm, a zeta potential of +23.3 mV, and an encapsulation efficiency of 81%. FTIR spectroscopy showed spectral changes compatible with morin incorporation and possible hydrogen-bonding interactions. The NPs exhibited approximately 81.4% morin release over 72 h in vitro. Compared to free morin, Morin-PLGA-CS NPs increased center-zone exploration in the OFT and open-arm behavior in the EPM, but also reduced total distance traveled in the OFT, indicating that motor suppression or sedation may have contributed to the behavioral profile (<i>p</i> < 0.001). It also improved the discrimination index (DI) in the NOR test and elevated sleep duration in the pentobarbital test (<i>p</i> < 0.001). The NPs also prolonged seizure latency (137.2 s vs. 114.5 s for free morin; <i>p</i> < 0.001) and markedly reduced IL-1β, IL-6, and TNF-α levels in both the cortex and hippocampus. At the molecular level, Morin-PLGA-CS NPs were associated with significantly increased hippocampal Nrf2 and HO-1 mRNA transcript levels and decreased GFAP and Iba1 transcript levels relative to free morin and the PTZ-challenged vehicle control group. <b>Conclusions:</b> Morin-PLGA-CS NPs produced greater behavioral, anticonvulsant, inflammatory, and redox effects than free morin in male rats. Molecular data revealed changes in hippocampal mRNA expression, including increased Nrf2 and HO-1 transcripts and decreased GFAP and Iba1 transcripts. However, these transcript-level findings are preliminary and require protein-level validation.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Spontaneous Urticaria in the Era of Targeted Therapy: From Pathogenic Mechanisms to Precision Medicine.","authors":"Klara Andrzejczak, Wiktor Witkowski, Joanna Górka-Dynysiewicz, Robert Pawłowicz, Agnieszka Kopeć","doi":"10.3390/pharmaceutics18091169","DOIUrl":"10.3390/pharmaceutics18091169","url":null,"abstract":"<p><p>Chronic spontaneous urticaria (CSU) is a common and heterogeneous inflammatory skin disease characterized by recurrent wheals and/or angioedema for more than six weeks. Despite treatment with second-generation antihistamines, many patients remain symptomatic, highlighting the need for therapies targeting underlying pathogenic mechanisms.</p><p><strong>Aim: </strong>This review summarizes current knowledge on CSU immunopathogenesis and targeted therapies, with a focus on personalized medicine.</p><p><strong>Methods: </strong>A literature review was conducted, focusing on recent advances in CSU endotypes and clinical trial data on biologic, small-molecule, and other targeted therapies acting on key immunological pathways.</p><p><strong>Results: </strong>CSU is increasingly recognized as a heterogeneous disease with distinct immunological endotypes, including type I (autoallergic) and type IIb (autoimmune), which may influence treatment response. Omalizumab remains the mainstay of second-line therapy, although many patients do not achieve complete disease control. Emerging therapies, including anti-IL-4Rα monoclonal antibodies (dupilumab), Bruton's tyrosine kinase inhibitors (e.g., remibrutinib), and anti-c-KIT monoclonal antibodies (e.g., barzolvolimab, briquilimab), have demonstrated promising efficacy. Some show a rapid onset of action, although preferential efficacy in specific CSU endotypes remains to be established. Several clinical and laboratory features, including total IgE, anti-TPO antibodies, ASST, basophil reactivity, basopenia, eosinopenia, and atopic comorbidities, have been investigated as potential markers of endotype and treatment response; however, their utility for treatment selection remains insufficiently validated.</p><p><strong>Conclusions: </strong>Advances in understanding CSU pathogenesis have enabled the development of targeted therapies that may improve disease control. Predictive biomarkers and endotypic characterization may support the future development of more personalized therapeutic strategies; however, clinically validated biomarkers for treatment selection remain limited, and prospective validation of biomarker-guided approaches is still needed.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do We Still Need Chemistry for Water-Soluble Prodrugs? What Biocatalysis Already Does, and What It Does Not.","authors":"Federico Zappaterra, Domenico Meola, Francesco Presini, Lindomar Alberto Lerin, Pier Paolo Giovannini","doi":"10.3390/pharmaceutics18091166","DOIUrl":"10.3390/pharmaceutics18091166","url":null,"abstract":"<p><p>Poor aqueous solubility limits roughly 40% of marketed oral drugs and up to ~90% of development candidates. One established remedy is the prodrug strategy: the covalent attachment of a bioreversible promoiety that regenerates the parent drug in vivo. The same conjugation can move a molecule in either direction along the hydrophilic-lipophilic axis: lipophilization raises membrane and oil solubility for permeation-limited or topical uses, whereas hydrophilization raises aqueous solubility. This review addresses hydrophilization and asks whether enzymatic (biocatalytic) synthesis can replace conventional chemistry in building water-soluble prodrugs. We examine, class by class of hydrophilic promoiety (polyol and sugar esters, glycosides, amino acid esters, poly(ethylene glycol), and ionizable phosphates), the biocatalytic toolbox (lipases, acyltransferases, glycosidases, and glycosyltransferases), the molecular determinants of its selectivity, the pharmacokinetic consequences of hydrophilization, and the translation of these reactions to process, benchmarking each against the corresponding chemical route. A three-part test emerges: enzymes suffice, and frequently surpass chemistry, wherever an accessible hydroxyl or carboxyl must be functionalized regioselectively on a promoiety bearing no competing group and a moderate solubility gain is required. This is the regime of polyols, most sugars, and glycosides, with drug-conjugate aqueous-solubility increases of roughly 4-fold to 5500-fold; chemistry remains necessary for ionizable phosphates, amino acid esters, and PEG carriers. Two gaps limit translation: the field's central 'green' claim is asserted far more often than it is measured (E-factor, PMI, life-cycle assessment), and in vivo pharmacokinetic data for enzymatically synthesized hydrophilizing prodrugs remain almost absent. We provide a decision flowchart that assigns each bond of a synthesis to biocatalysis or to chemistry, and reporting guidelines for the seven quantities that make a published E-factor recoverable.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering of OHet72 Nanocrystals into Nanostructured Microparticles for Pulmonary Delivery of a Novel Antitubercular Drug Candidate.","authors":"Margaret D Bourlon, Alexa Beathard, Lucila Garcia-Contreras","doi":"10.3390/pharmaceutics18091164","DOIUrl":"10.3390/pharmaceutics18091164","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Current treatments for tuberculosis (TB) are complex and associated with severe side effects; thus, drugs with minimal side effects would be desirable as additions to current therapies to combat the global TB epidemic. OHet72 is a novel compound with in vitro activity against <i>Mycobacterium tuberculosis</i> but has poor water solubility. As a first step in assessing its potential for TB treatment, the goal of this study was to formulate OHet72 in a powder form that will increase its solubility compared to the unprocessed drug, and when aerosolized, ensure that most of the inhaled dose would be deposited in the alveoli. <b>Methods</b>: OHet72 was first formulated into nanocrystals (NCs) and then spray-dried to obtain nanostructured microparticles (nsMPs). The resulting formulations were characterized in vitro, and their rate of dissolution was assessed. <b>Results</b>: OHet72 NCs were oblong-shaped with an average width of 145 nm and a length of 255 nm, whereas the resulting nsMPs were spherical, with a geometric diameter of 0.64 μm and a GSD of 1.54. When aerosolized with the Pari LC^® Star nebulizer, a suspension of OHet72 NCs in saline had a mass median aerodynamic diameter (MMAD) of 3.15 ± 0.43 μm and a fine particle fraction (FPF, indicating the fraction that will likely be deposited in the alveoli) of 54.63 ± 5.83%. In contrast, OHet72 nsMPs dispersed from the Plastiape RS01 dry powder inhaler (DPI) had a MMAD of 3.80 ± 0.49 μm and an FPF of 37.16 ± 6.67%. The dissolution rate of OHet72 NCs was faster (34.65 ± 5.43%) than that of the unprocessed drug (0.72 ± 0.34%), but the OHet72 in the nsMPs dissolved significantly faster and to a greater extent (57.55 ± 5.60%) than both the unprocessed drug and the NCs. <b>Conclusions</b>: Based on their MMAD, GSD and FPF, OHet72 NC and nsMPs appear suitable for effective pulmonary delivery, and based on their apparent solubility and dissolution testing, they would dissolve in the lung environment.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reductant-Responsive Squalene Dual-Prodrug Nanoparticles Co-Delivering Doxorubicin and Exatecan for Synergistic Breast Tumor Therapy.","authors":"Li Wang, Ning Yang, Yina Sa, Zhenghua Li, Yanlong Qiao, Yanxin Yang, Lixue Chen, Xiangyu Liu, Lei Li","doi":"10.3390/pharmaceutics18091155","DOIUrl":"10.3390/pharmaceutics18091155","url":null,"abstract":"<p><p><b>Background</b>: combination chemotherapy employing agents with complementary mechanisms of action can enhance therapeutic efficacy and overcome resistance, but mismatched pharmacokinetics and systemic toxicity limit benefit. <b>Methods</b>: We designed reductant-responsive squalene prodrugs of doxorubicin (DOX) and exatecan (EXA) that co-assemble with DSPE-PEG_2k into approximately 76 nm dual-prodrug nanoparticles (doxorubicin prodrug-exatecan prodrug nanoparticles, DP-EP NPs) at a predefined synergistic ratio 1:2. <b>Results</b>: The minimalist, drug-as-carrier formulation achieved high effective loadings with minimal leakage under normoxia, yet synchronously liberated both drugs in reductive, hypoxia-mimicking media (24 h release: DOX ~65% and EXA ~58% at 1 mM Na₂S₂O₄ vs. ~8-11% at 0 mM Na₂S₂O₄). In MCF-7 and 4T1 cells, the nanoparticles enhanced intracellular accumulation, intensified the disruption of DNA damage repair, as evidenced by increased colocalization of 53BP1 and enhanced γ-H2AX foci, and induced markers of immunogenic cell death, including increased CRT-associated cellular fluorescence and reduced intracellular HMGB1 staining. Furthermore, they partially reversed drug resistance in MCF-7/ADR cells. In rats, the formulation prolonged circulation and increased exposure (DOX t_½ ~9×, AUC ~1.8×; EXA t_½ ~5×, AUC ~14.9×) relative to the free-drug mixture. In 4T1 tumor-bearing mice, the nanoparticles produced the greatest tumor-growth inhibition with improved tolerability, supported by stable body weight and benign histopathology. <b>Conclusions</b>: These findings establish a scalable, excipient-lean platform that aligns pharmacokinetics with microenvironment-triggered pharmacodynamics to deliver synchronized Topo II/I inhibition for synergistic chemotherapy.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrospun Integrated Janus Nanofibers for Asynchronous Delivery of Finasteride and Tibetan Medicine.","authors":"Qilin Wang, Tingyu Chen, Hailong Dou, Deng-Guang Yu","doi":"10.3390/pharmaceutics18091160","DOIUrl":"10.3390/pharmaceutics18091160","url":null,"abstract":"<p><p><b>Background</b>: Simultaneous controlled release of multiple therapeutics from a single dosage form is a major frontier in modern pharmaceutics and a key strategy for modernizing traditional Chinese medicine. <b>Methods</b>: Using finasteride (FIN) and a Jing-Zhu hybrid Tibetan (JZ) herbal medicine as model agents for prostatitis therapy, we developed a modified tri-fluid electrospinning process to fabricate drug-co-loaded Janus medicated nanofibers. Soluble polyvinylpyrrolidone (PVP) and insoluble ethylcellulose (EC) served as carrier matrices for the dual faces of the Janus architecture, encapsulating JZ herbal medicine and FIN, respectively. A custom-designed spinneret-comprising two parallel stainless steel tubes nested within a plastic sheath-was engineered to enable side-by-side fiber formation. <b>Results</b>: Scanning and transmission electron microscopy confirmed linear morphologies with a definitive side-by-side Janus structure. X-ray diffraction and Fourier Transform Infrared Spectroscopy revealed that all active ingredients were dispersed in an amorphous state, reflecting polymer-drug compatibility. Encapsulation efficiencies reached 96.34 ± 0.47% for FIN and 94.15 ± 0.48% for JZ herbal medicine. A newly devised water-droplet assay demonstrated that almost all the nanofibers exhibited the intended side-by-side configuration, as evidenced by the rapid dissolution of the PVP side. In vitro release studies showed an initial pulsatile burst of JZ herbal medicine followed by a sustained FIN release profile, as suggested by the single-drug-loaded Janus nanofibrous controls. <b>Conclusions</b>: The present Janus nanostructure system, fabricated via a facile co-shell solvent electrospinning process, has the potential to enable the concurrent yet asynchronous delivery of FIN and JZ herbal components within a single nano-dosage form. This conceptual advance expands the toolkit for designing combination nanomedicines, allowing independent modulation of release kinetics for individual drugs to maximize prospective joint efficacy.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a Fluorescence-Based High-Throughput Screening Method for Natural Product Fractions to Identify Inhibitors of AR-V7 for Castration-Resistant Prostate Cancer.","authors":"Neha Tyagi, Manish Rathi, Susan Ensel, Christopher C Thornburg, Tanja Grkovic, Barry R O'Keefe, James C Sacchettini, Chendil Damodaran","doi":"10.3390/pharmaceutics18091158","DOIUrl":"10.3390/pharmaceutics18091158","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The progression of prostate cancer to castration-resistant prostate cancer (CRPC) is often driven by constitutively active androgen receptor splice variants, such as AR-V7, which evade conventional androgen-deprivation therapies. This study aimed to develop a high-throughput, mechanism-based screening platform to identify natural-product-derived AR-V7 inhibitors from the NCI Program for Natural Product Discovery (NPNPD) library. <b>Methods:</b> A subset of prefractionated NPNPD samples was screened using a CRISPR-edited 22Rv1 cell line expressing endogenous AR-V7 fused to a HiBiT luminescent tag, enabling quantification of AR-V7 levels. Fractions that reduced the HiBiT signal were further evaluated in 22Rv1 and C4-2B CRPC cells and counter-screened in non-malignant RWPE-1 cells. Compounds demonstrating at least 90% inhibition in CRPC cells with no more than 10% toxicity in RWPE-1 cells underwent dose-response analysis, Western blotting, quantitative PCR, and subfractionation to isolate and characterize active constituents. <b>Results:</b> Of the 704 prefractionated samples, five fractions met stringent activity and selectivity criteria, with three consistently suppressing full-length androgen receptor (AR), AR-V7, and prostate-specific antigen (PSA). Primary screening results in HiBiT-22Rv1 cells were validated by secondary dose-response and Western blot assays, and hits were further prioritized to ensure toxicity remained at or below 10% in RWPE-1 cells. HiBiT-guided screening of 66 subfractions identified seven that robustly downregulated AR signaling, with reduced AR-V7 levels correlating with decreased CRPC cell viability. Chemical characterization revealed two active butanolides, isolitsealiicolide C and isolinderanolide B, which reduced AR and AR-V7 protein and mRNA levels, decreased PSA, downregulated Bcl-2, and induced cleaved PARP, consistent with apoptotic cell death in AR-positive CRPC models. <b>Conclusions:</b> This integrated high-throughput workflow efficiently identifies AR-V7-targeted natural products from complex libraries and highlights isolitsealiicolide C and isolinderanolide B as promising scaffolds for overcoming androgen receptor-driven resistance in CRPC.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Therapeutic Drug Monitoring to Model-Informed Precision Dosing: A Review of Busulfan Dosing Optimization in Pediatric Hematopoietic Stem Cell Transplantation.","authors":"Xiao-Ying Zhang, Yue Li, Jing Xu, Yong-Jun Fang, Xuan-Sheng Ding, Feng Chen","doi":"10.3390/pharmaceutics18091154","DOIUrl":"10.3390/pharmaceutics18091154","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Busulfan is a cornerstone conditioning agent for pediatric hematopoietic stem cell transplantation (HSCT), yet its narrow therapeutic index and substantial pharmacokinetic (PK) variability complicate dosing. This review synthesizes current evidence on pediatric busulfan PK, exposure-guided dosing, and the transition from conventional therapeutic drug monitoring (TDM) to model-informed precision dosing (MIPD). <b>Methods</b>: We conducted a focused narrative search of PubMed, Web of Science, and ScienceDirect from database inception to August 2026 and synthesized relevant literature on pediatric busulfan PK, exposure-response relationships, TDM, population PK modeling, Bayesian methods, and emerging quantitative approaches. <b>Results</b>: Body size is the primary determinant of busulfan clearance in children, while maturation, underlying disease, concomitant medications, and pharmacogenetic variation may contribute additional variability, although their effects are inconsistent across populations. Busulfan exposure is associated with HSCT outcomes and toxicity; however, reported targets differ by dosing regimen, conditioning intensity, disease category, and exposure metric. Reliable exposure estimation requires accurate sampling records and validated bioanalysis, while limited sampling strategies may improve clinical feasibility. Integrating population PK models with Bayesian estimation enables individualized dose adjustment, although routine implementation requires external validation and compatibility with local workflows. Emerging approaches, including physiologically based PK, PK/PD, and machine learning models, show promise but lack sufficient clinical validation for routine use. <b>Conclusions</b>: TDM remains the foundation of pediatric busulfan precision dosing, while MIPD provides a framework for integrating patient characteristics, measured concentrations, and validated models. Standardized workflows, population-appropriate exposure targets, prospective validation, and evidence of improved clinical outcomes are essential for broader implementation.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-Mediated Silver Nanoparticle Formulations for Wound Healing: A Process-Property-Performance Perspective.","authors":"Mohammad Moein Sadeghi, Souha Idoudi, Helena M Kelly, Nashiru Billa","doi":"10.3390/pharmaceutics18091161","DOIUrl":"10.3390/pharmaceutics18091161","url":null,"abstract":"<p><p>Biomaterials intended for wound healing are expected to reduce microbial load while supporting tissue repair in complex wound environments. Plant-mediated synthesis of silver nanoparticles (AgNPs) has attracted interest because plant extracts can provide phytochemicals that mediate nanoparticle reduction, capping, and stabilization. This review critically evaluates recent studies on plant-mediated AgNPs for wound-healing applications, focusing on botanical and extraction variables, synthesis conditions, physicochemical properties, formulation strategies, administered exposure, safety, and biological outcomes. Across the 34 included publications, 14 directly assessed a process-to-property relationship and only two assessed a process-to-performance relationship; none directly assessed a property-to-performance relationship or established a complete process-to-property-to-performance chain. The reviewed studies suggest that plant-mediated AgNPs may reduce microbial burden, modulate inflammation, mitigate oxidative stress, and promote cell migration, re-epithelialization, collagen remodeling, and angiogenesis. However, batch-to-batch variability, incomplete reporting of experimental details, over-reliance on ultraviolet-visible (UV-Vis) spectroscopy for optimization, inadequate evaluation of formulation stability, inconsistent dose reporting, and limited molecular validation of proposed mechanisms remain major factors limiting translation. By evaluating plant-mediated AgNP-based wound-healing systems through a process-property-performance framework, this review summarizes recent advances and highlights key considerations for improving reproducibility, comparability, and translational relevance.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}