Journal of Pharmaceutical Innovation最新文献

{"title":"Integrated Machine Learning and Structure-Based Computational Discovery of Natural Product Inhibitors Targeting the METTL3 m6A Methyltransferase for Cancer Drug Discovery","authors":"Ziyad Tariq Muhseen,&nbsp;Hussen Hazim Al-Ghanini,&nbsp;Roaa A. Humaidan,&nbsp;Zahraa Yousif Al-Hajjaj,&nbsp;Ola H. Fadhil","doi":"10.1007/s12247-026-11126-4","DOIUrl":"10.1007/s12247-026-11126-4","url":null,"abstract":"<div><h3>Objective </h3><p>To identify novel phytochemical inhibitors of methyltransferase-like 3 (METTL3), a key regulator of N6-methyladenosine (m6A) RNA methylation implicated in cancer development, using an integrated computational drug discovery approach.</p><h3>Methods</h3><p>Five supervised machine learning models were trained using 88 active METTL3 inhibitors and 440 inactive decoy compounds. The best-performing models were used to screen 2,347 phytochemicals from the MPD3 library, followed by consensus-based candidate selection and Lipinski’s Rule of Five filtering. Molecular docking was performed against the METTL3 co-crystal structure (PDB: 9G4S), followed by absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling. Three selected compounds underwent 100 ns all-atom molecular dynamics (MD) simulations, with complex stability assessed using root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), hydrogen-bonding analysis, principal component analysis (PCA), and trajectory snapshots. Molecular mechanics generalized Born surface area (MM-GBSA) calculations were performed to estimate binding free energies.</p><h3>Results</h3><p>Random Forest (area under the receiver operating characteristic curve [AUC] = 0.917) and Gradient Boosting (AUC = 0.911) demonstrated the highest predictive performance. Consensus screening identified 75 high-probability candidates. Molecular docking revealed five top-ranked compounds with scores ranging from −10.0 to −11.3 kcal/mol, demonstrating interactions with key catalytic residues, including Asp395, His512, Asn549, and Gln550. Following ADMET assessment, PubChem637406 and PubChem162892281 were excluded due to predicted AMES mutagenicity. MD simulations indicated that PubChem31553 and PubChem5280704 maintained stable interactions within the METTL3 S-adenosylmethionine (SAM)-binding pocket, whereas PubChem11669392 exhibited unstable interactions and eventually dissociated from the active site. MM-GBSA calculations yielded estimated binding free energies of −28.70 ± 5.91 kcal/mol for PubChem31553 and −27.23 ± 3.26 kcal/mol for PubChem5280704, comparable to the reference inhibitor (−27.93 ± 2.35 kcal/mol). In contrast, PubChem11669392 exhibited a less favorable estimated binding free energy of −13.70 ± 3.19 kcal/mol.</p><h3>Conclusions</h3><p>The integrated computational screening workflow identified PubChem31553 and PubChem5280704 as promising candidate scaffolds for METTL3 inhibition, supported by favorable docking scores, stable MD trajectories, and estimated binding free energies comparable to those of the reference inhibitor. These findings provide a foundation for experimental validation of these compounds and their potential development as leads for m6A-targeted anticancer drug discovery. Further biochemical and cellular studies are required to confirm their inhibitory activity, selectivity, and therapeutic potential.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Development of Separate Sodium Caseinate Nanoparticle Formulations of 5-Fluorouracil and 5-Fluorouracil-1-acetic Acid: Physicochemical, In Vitro, and Ex Vivo Evaluation","authors":"Nisha Agari Bhatt,&nbsp;Ashok Behera,&nbsp;Aman Chaudhary,&nbsp;Jhuma Samanta","doi":"10.1007/s12247-026-11119-3","DOIUrl":"10.1007/s12247-026-11119-3","url":null,"abstract":"<div><h3>Purpose</h3><p>This study aimed to develop and optimize separate sodium caseinate nanoparticles containing 5-fluorouracil (5-FU) and 5-fluorouracil-1-acetic acid (5-FUA), and to evaluate their properties.</p><h3>Methods</h3><p>Nanoparticles were prepared using calcium-ion-induced crosslinking. Separate three-factor, three-level Box–Behnken designs were used to optimize CAS-5FU and CAS-5FUA nanoparticles using entrapment efficiency and drug loading as responses. Formulations were characterized for particle size, polydispersity index, zeta potential, drug release, serum stability, antioxidant activity, hemocompatibility, ex vivo intestinal permeation, and HeLa-cell cytotoxicity.</p><h3>Results</h3><p>The optimized CAS-5FU and CAS-5FUA nanoparticles showed entrapment efficiencies of 94.70% and 28.46%, respectively, and drug-loading values of 57.00% and 15.65%, respectively. Mean particle sizes were 210 ± 12 and 195 ± 10 nm, with PDIs of 0.26 ± 0.03 and 0.24 ± 0.02, respectively. CAS-5FU nanoparticles produced a 1.42-fold higher cumulative permeated amount per unit intestinal surface area than free 5-FU (14.52 versus 10.25 µg/cm²) under these conditions. CAS-5FUA nanoparticles did not enhance permeation compared with free 5-FUA (12.5 versus 13.5 µg/cm²). Both formulations exhibited prolonged, pH-dependent release, short-term serum physicochemical stability, and less than 5% hemolysis. CAS-5FU showed greater chemical radical-scavenging activity than CAS-5FUA. Both formulations produced concentration-dependent reductions in HeLa-cell viability, with estimated IC₅₀ values of approximately 250 and 240 µM, respectively.</p><h3>Conclusion</h3><p>CAS-5FU nanoparticles showed higher entrapment efficiency, drug loading, cumulative ex vivo permeation, and chemical radical-scavenging activity than CAS-5FUA nanoparticles. The results confirm their potential as nanocarriers, but more comparative and in vivo studies are needed.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VEGF-binding V7t1 Aptamer Conjugate for Dual Modulation of Angiogenesis and MMP-2 in CRC","authors":"Ashwin Ravichandran,&nbsp;Aishwarya Reddy,&nbsp;Sai Varshini Magham,&nbsp;Avinash Kumar,&nbsp;Pravallika P","doi":"10.1007/s12247-026-11115-7","DOIUrl":"10.1007/s12247-026-11115-7","url":null,"abstract":"<div><h3>Background</h3><p>Colorectal cancer (CRC) ranks among the leading causes of cancer-related mortality worldwide, with lifestyle factors such as poor diet, high red meat consumption, and physical inactivity contributing to its incidence. Conventional chemotherapeutic agents, including 5-fluorouracil, irinotecan, and oxaliplatin, have limitations associated with non-targeted action and systemic adverse effects. Consequently, precision medicine approaches targeting molecular pathways involved in tumor growth and metastasis have gained considerable attention. Matrix metalloproteinase-2 (MMP-2) plays a pivotal role in tumor invasion and angiogenesis and is markedly overexpressed in CRC.</p><h3>Objective</h3><p>This review discusses the potential of targeting MMP-2 using doxycycline and the application of the V7t1 DNA aptamer as a VEGF-targeting ligand for developing a targeted therapeutic strategy against CRC.</p><h3>Methods</h3><p>Published literature concerning MMP-2 in CRC, the MMP-inhibitory activity of doxycycline, V7t1 DNA aptamer-mediated targeting, VEGF, angiogenesis, metastasis, and targeted drug delivery was reviewed and critically evaluated. Available in silico and preclinical findings relevant to the proposed therapeutic approach were also considered.</p><h3>Results</h3><p>Doxycycline, a tetracycline antibiotic with reported MMP-inhibitory activity, represents a potential drug-repurposing strategy rather than an approved anticancer indication. Its MMP-modulating activity may involve metal-ion chelation as well as effects on MMP expression and pro-MMP activation. The V7t1 DNA aptamer has demonstrated specificity toward VEGF, particularly VEGF121 and VEGF165, and may facilitate targeted delivery. Published in silico studies have reported favorable interactions between V7t1 and VEGF, while preclinical studies have indicated selective inhibition of cancer cell proliferation and angiogenesis with comparatively limited effects on normal cells. The proposed therapeutic system, designated DH–V7t1, is a direct aptamer conjugate in which V7t1 serves as the VEGF-targeting ligand and doxycycline hyclate provides MMP-inhibitory activity. These mechanisms are distinct but potentially complementary and may improve therapeutic selectivity and efficacy.</p><h3>Conclusion</h3><p>The DH–V7t1 system represents a proposed preclinical therapeutic concept for combining VEGF-targeted delivery with MMP inhibition in CRC. However, its conjugation efficiency, structural integrity, release behavior, targeting ability, pharmacokinetics, biodistribution, safety, and therapeutic efficacy require experimental validation before its translational potential can be established.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>Proposed mechanism of action of the DH–V7t1 aptamer conjugate in CRC</p></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manufacturing Readiness and Route Reconfiguration in Therapeutic Radiopharmaceutical Development: A Multiple-Case Process Study","authors":"Soon Kyu Jung,&nbsp;Sang-Won Lee","doi":"10.1007/s12247-026-11129-1","DOIUrl":"10.1007/s12247-026-11129-1","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;p&gt;Therapeutic radiopharmaceuticals require isotope procurement, radiolabeling, quality control, transport, and patient administration to be coordinated within time windows constrained by radioactive decay. This study examines how manufacturing readiness develops as manufacturing routes are established and reconfigured across clinical development and commercialization, distinguishing access to a manufacturing route from product-specific preparation and documented product-level use.&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;A multiple-case process study analyzed 14 therapeutic radiopharmaceutical product cases and 51 documented events identified through August 1, 2026. Thirty-six events were directly linked to a specific product. Twelve cases with at least two product-related events formed the core comparative sample. Within-case timelines, cross-case comparison, and sequence and interval analysis were used to examine manufacturing access, product-specific readiness, actual production/supply, route addition, and supply-status changes.&lt;/p&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Four cases showed product-related manufacturing or supply events 89–683 days before entry into clinical development. In four cases, company-level facilities were used for actual production/supply 62–1,348 days after they were secured. Nine cases recorded 14 manufacturing or supply changes 174–3,977 days after entry into clinical development. In-house, regional, and external routes were added in different sequences, including among products using the same radionuclide. Post-approval observations also distinguished site approval, production interruption, restart, and shortage resolution as separate events.&lt;/p&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;Manufacturing readiness in therapeutic radiopharmaceutical development is better understood as a product–route process than as a binary firm-level capability. A contract or facility creates manufacturing access, but product-specific preparation and documented use may occur later, and the process may recur when routes are added during development or commercialization.&lt;/p&gt;&lt;h3&gt;Summary&lt;/h3&gt;&lt;p&gt;This study reconstructs how therapeutic radiopharmaceutical manufacturing routes were established, connected to product-level use, and expanded across development. Fourteen cases and 51 documented events show that facility or contract access did not automatically coincide with product-level use. In four cases, securing a company-level facility and actual production/supply at that facility were separated by 62–1,348 days, while manufacturing changes continued years after entry into clinical development. The findings support a product–route view of manufacturing readiness and distinguish structural route availability from operational usability.&lt;/p&gt;&lt;h3&gt;Teaser&lt;/h3&gt;&lt;p&gt;Manufacturing access does not ensure product-level readiness: therapeutic radiopharmaceutical routes become operational through product-specific preparation, documented use, and route reconfiguration across clinical developmen","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation and Evaluation of Oral Anti-IL-1β IgY-Loaded Nanoliposomes in DSS-Induced Colitis","authors":"Guiying Dai,&nbsp;Wenjing Xu,&nbsp;Youdan Sun,&nbsp;Xiaoyan Zheng,&nbsp;Changsheng Chen,&nbsp;Fang Gan,&nbsp;Yunhuan Liu,&nbsp;Xinyi Xu,&nbsp;Sichao Mao,&nbsp;Xingxiang Chen","doi":"10.1007/s12247-026-11127-3","DOIUrl":"10.1007/s12247-026-11127-3","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;p&gt;To develop an oral nanoliposomal formulation of anti-interleukin-1β (IL-1β) immunoglobulin Y (IgY) and evaluate its physicochemical properties, gastric stability, and activity in dextran sulfate sodium (DSS)-induced colitis.&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Recombinant canine IL-1β was expressed and used to immunize hens. Purified IgY was loaded into 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol nanoliposomes by thin-film hydration. Encapsulation efficiency, particle characteristics, morphology, and residual IgY antigen-binding activity in simulated gastric fluid were assessed. Male Institute of Cancer Research (ICR) mice with DSS-induced colitis received free IgY, empty liposomes, or IgY-loaded nanoliposomes. Disease activity, organ indices, colonic cytokines, histopathology, and Occludin and ZO-1 expression were evaluated.&lt;/p&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;The IgY showed a maximum endpoint titer of 1:409,600, recognized recombinant canine IL-1β, and showed detectable cross-reactivity with recombinant murine IL-1β by Western blotting. Nanoliposomes achieved approximately 56% encapsulation efficiency, a polydispersity index of approximately 0.35, negative ζ-potential, and intact vesicular morphology. At 150 min in simulated gastric fluid, two parallel samples from the same liposomal preparation retained 43.96% and 35.98% antigen-binding activity, respectively. In DSS-treated mice, the formulation was associated with improved clinical indices, lower colonic IL-1β, IL-6, and TNF-α levels, less histopathological injury, and recovery of barrier-protein staining.&lt;/p&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;Nanoliposomal encapsulation improved the in vitro gastric stability of anti-IL-1β IgY and was associated with anti-inflammatory and barrier-protective effects in DSS-induced experimental colitis. Western blotting demonstrated detectable cross-reactivity of the anti-canine IL-1β IgY with recombinant murine IL-1β; however, functional neutralization of murine IL-1β was not directly assessed.&lt;/p&gt;&lt;h3&gt;~ 100 Word Summary Anti-IL-1β IgY &lt;/h3&gt;&lt;p&gt;is a potential oral antibody strategy for intestinal inflammation, but gastric instability limits its use. In this study, IgY raised against recombinant canine IL-1β was incorporated into DSPC/cholesterol nanoliposomes and evaluated for physicochemical properties, simulated gastric stability, and activity in DSS-induced colitis. The formulation achieved approximately 56% encapsulation efficiency and retained substantially more IgY antigen-binding activity than free IgY during gastric exposure. In mice, IgY-loaded nanoliposomes were associated with improved disease indices, reduced colonic cytokines, less histopathological injury, and recovery of Occludin and ZO-1 staining. These findings support nanoliposomal protection of IgY during oral delivery, and detectable cross-reactivity with recombinant murine IL-1β was further confirmed by Western blotting.&lt;/p&gt;&lt;h3&gt;25–30 Word Teaser &lt;/h3&gt;&lt;p&gt;Nanoliposomal encapsulation improve","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-Dimensional SiHa Tumor Spheroids for Evaluating Berberis aquifolium-Loaded Chitosan Nanoparticles in Cervical Cancer","authors":"Aadipoojya Jain,&nbsp;Deepika Sharma,&nbsp;Areena Turk,&nbsp;Tejveer Singh","doi":"10.1007/s12247-026-11110-y","DOIUrl":"10.1007/s12247-026-11110-y","url":null,"abstract":"<div><h3>Objective</h3><p>The present study aims to develop a chitosan nanoparticle-based delivery system encapsulating <i>Berberis aquifolium</i> (BA) extract to evaluate its anticancer activity against cervical cancer cells using conventional two-dimensional (2D) cultures and three-dimensional (3D) tumor spheroids models.</p><h3>Methods</h3><p><i>Berberis aquifolium</i>-loaded chitosan nanoparticles (BCNPs) were prepared using ionic gelation with sodium tripolyphosphate and characterized for hydrodynamic particle size, polydispersity index (PDI), zeta potential, and morphology. extract was encapsulated in chitosan nanoparticles using an appropriate nanoformulation technique. The anticancer activity of the BCNPs was evaluated in SiHa cervical cancer cells using the MTT assay. A 3D SiHa spheroid model was established and used to assess treatment-associated changes in spheroids morphology and structural integrity.AO/EtBr staining was used for qualitative assessment of cell viability and morphological changes. The response of primary goat hepatocytes and testicular cells to the formulation was also evaluated as an initial assessment of its effects on non-cancerous cells.</p><h3>Results</h3><p>BCNPs showed an average hydrodynamic diameter of 399.9 nm, PDI of 0.20, and zeta potential of -41.1 mV, compared with 413.2 nm, 0.30, and − 17.0 mV, respectively, for blank chitosan nanoparticles. The nanoparticles exhibited predominantly spherical morphology. BCNPs treatment produced a concentration-dependent reduction in SiHa cell viability, with an IC50 of 350 µg/mL. In the 3D spheroid model, BCNPs treatment progressively disrupted spheroid structure, with complete spheroid disintegration observed at 750 µg/mL. AO/EtBr staining showed loss of cell viability and morphological features suggestive of apoptosis.</p><h3>Conclusions</h3><p>The study demonstrated the successful development of BCNPs with anticancer activity against SiHa cervical cancer cells in both 2D and 3D models. The 3D spheroid model provided complementary information on treatment-associated changes in tumor-like spheroid structure and viability, supporting its utility for evaluating the anticancer activity of BCNPs. Further mechanistic and in vivo studies are required to establish their therapeutic potential.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning-Guided Discovery of Potential Natural KRAS-G12D Inhibitors for Pancreatic Carcinoma","authors":"Ali Alquraini,&nbsp;Mohammed Alahmari,&nbsp;Faisal K Alkholifi,&nbsp;Yahia Alghazwani,&nbsp;Marwa Qadri,&nbsp;Fadhel A. Alomar,&nbsp;Daniyah A. Almarghalani,&nbsp;Mohd Imran","doi":"10.1007/s12247-026-11123-7","DOIUrl":"10.1007/s12247-026-11123-7","url":null,"abstract":"<div><h3>Background</h3><p>The mutation KRAS-G12D found in pancreatic cancer is one of the biggest barriers to developing targeted therapy against pancreatic cancer. This research work tries to discover the potential KRAS-G12D inhibitors through natural products guided by machine learning approaches.</p><h3>Methods</h3><p>The screening process involved a library of 3,634 natural compounds sourced from the SelleckChem database, which were then filtered using the established QSAR model. Among these compounds, 176 potential compounds with appropriate predicted activities (pIC50) were chosen for subsequent testing. The 176 compounds were then docked against the switch-II pocket of the KRAS-G12D mutant protein. Compounds exhibiting docking scores equal to or lower than that of the reference inhibitor MRTX1133 (− 8.9 kcal/mol) were selected for subsequent ADMET and molecular dynamics analyses. The potential candidates were analyzed for their ADMET properties and binding interactions in silico. Further validation of the selected compounds was done by performing a molecular dynamics simulation for 300 ns along with a reference compound.</p><h3>Results</h3><p>KR1 and KR2 compounds were observed to have stable binding to the KRAS-G12D protein with RMSD values between 0.18 nm and 0.25 nm. MM-GBSA binding free energy calculations revealed a favorable interaction with energy levels of -13.57 kcal/mol and − 20.48 kcal/mol, respectively. The DFT analysis revealed that KR1 is more chemically stable due to high HOMO-LUMO gap values (4.669 eV) and low electrophilicity values (0.92 eV). However, KR2 was found to have balanced reactivity properties, with a relatively high electronegativity value (3.537 eV) and ionization potential value (4.828 eV).</p><h3>Conclusion</h3><p>Overall, these computations support the potential of KR1 and KR2 as valuable potential lead compounds of KRAS-G12D. Clearly, these results provide a robust basis for subsequent experimentation to validate their biological effects and therapeutic potential.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemical Profiling and Bioactive Potential of Lagochilus seravschanicus: Antioxidant, Anti-Diabetic, Anti-Hemolytic, Cytotoxicity, Phytotoxicity and Antimicrobial Activities","authors":"Sanam Ashraf,&nbsp;Zubaria Tul Ain,&nbsp;Sampath Chinnam,&nbsp;Javed Iqbal,&nbsp;Banzeer Ahsan Abbasi,&nbsp;Sobia Kanwal,&nbsp;Ghulam Murtaza,&nbsp;Mohsin Kazi,&nbsp;Tariq Mahmood","doi":"10.1007/s12247-026-10741-5","DOIUrl":"10.1007/s12247-026-10741-5","url":null,"abstract":"<div><p>Scientists are researching the therapeutic potential of herbal plants, which frequently leads to the identification of novel plants and bioactive chemicals that can be used in the development of new drugs. Natural phytochemicals are non-toxic, and their medicinal properties keep them in demand as alternative treatments for a variety of ailments. This motivated many researchers to explore plants in order to find bioactive compounds with significant pharmacological activities. Therefore, this research was performed to compare phytochemical profiling and biological activity of chloroform and methanolic extracts of roots, leaves, and flowers of the <i>Lagochilus seravschanicus</i> plant growing in Gilgit-Baltistan, Pakistan. Phytochemical screening showed the existence of 21 secondary metabolites and over fourteen functional groups of the FT-IR spectroscopy in all extracts of the plant. The quantitative analysis exhibited the maximum phenolic (76.24 ± 0.01 GAE mg/g) and flavonoid (74.53 ± 0.01 GAE mg/g) content in methanolic leaf extracts. Methanolic flower extract (LSFM) displayed the antioxidant capacity of (83.32 ± 0.50 mg AAE/g), followed by leaf methanolic extract (LSLM) that displayed moderate cytotoxicity against HeLa cells with an IC₅₀ value of 278 µg/mL. The leaf methanolic extract (LSLM) also exhibited significant anti-diabetic capacity (51.94%) by α-amylase inhibition and the high anti-hemolytic capacity of (90.24 ± 0.58%) on the human red blood cells. Moderate phytotoxicity was observed in leaf extracts (15%), lowering the germination of radish seeds. The findings showed that <i>L. seravschanicus</i> extracts displayed resistance against every bacterial and fungal strain. The maximum inhibitory zone was displayed by LSLM (18 ± 0.5 mm) against <i>E. faecalis</i>,<i> B. subtilis</i>,<i> B. atrophaeus</i>,<i> and S. aureus.</i> For antifungal activity, the highest ZOI exhibited by chloroform leaf extract (LSLC) against <i>A. fumigatus</i> and <i>A. niger</i> (17 ± 0.5 mm ZOI). These results suggest that <i>L. seravschanicus</i> has bioactive compounds possessing antioxidant, anticancer, antimicrobial, and enzyme-inhibitory potential and can serve as a source of pharmacological agents in the future.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Injectable and Photocrosslinked Methacrylate Gelatin/ Pluronic F127 Diacrylate Hydrogel Enhanced Articular Cartilage Regeneration in Osteoarthritis","authors":"Zhen-wei Li,&nbsp;Guan-sheng Han,&nbsp;Chen Shao,&nbsp;De-gui Xu,&nbsp;Tian-chen Yao,&nbsp;Zheng-lin Hu","doi":"10.1007/s12247-026-11063-2","DOIUrl":"10.1007/s12247-026-11063-2","url":null,"abstract":"<div><p>Osteoarthritis (OA) is a degenerative condition marked by the deterioration of articular cartilage, usually linked to mechanical joint damage. MMPs play a crucial role in the cartilage degradation observed in OA patients. This study developed an injectable hydrogel (IHG) composed of a mechanically resilient, reverse-thermo-sensitive F127DA (FD) and an MMP-responsive, thermo-sensitive gelatin methacryloyl (GM). The IHG was engineered to deliver TGF-β and KG with precise control via temperature manipulation. The hydrophobic properties of FD and hydrophilic properties of GM provide effective intra-articular distribution of various drugs, thereby enhancing their therapeutic efficacy. In situ photocrosslinking of the IHG occludes cartilage damage and inhibits deterioration. The overexpression of MMP in the OA milieu induces TGF-β release, attracting bone marrow mesenchymal stromal cells (BMDSCs), and mechanical stress from the joint actions liberates KG, alleviating inflammation and facilitating chondrogenic differentiation. The proposed IHG, responsive to mechanical stress and the osteoarthritic micromilieu, can improve OA cartilage regeneration. This methodology exhibits considerable promise for progressing osteoarthritic cartilage engineering.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetic Nanoparticles for Theranostic Nanomedicine: A Novel Barrier-Route-Stimulus Design Framework, Complexity-Translatability Heuristic and Translational Evidence in Seven Disease Contexts","authors":"Rupak Sarkar,&nbsp;Kundan Singh Bora,&nbsp;Hitesh Kumar Dewangan","doi":"10.1007/s12247-026-11073-0","DOIUrl":"10.1007/s12247-026-11073-0","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Magnetic Nanoparticles (MNPs), of which Superparamagnetic iron oxide nanoparticles (SPIONs) are the most clinically mature subclass, represent a class of cutting-edge theranostic platforms in that they simultaneously integrate drug delivery and AMF-hyperthermia alongside live MR imaging. Although SPIONs (magnetite/maghemite) are used as the base focus here, the performance of cobalt ferrites, permalloy alloys, and gadolinium-doped variants in context as the defining boundaries between material-specific design rules is presented here. Non-selective biodistribution and systemic toxicity plagued traditional pharmacotherapy, which SPIONs fundamentally countered through their favourable but context-dependent biocompatibility that requires careful evaluation of lysosomal iron release, ferroptotic risk, and route-dependent toxicity, tunable surface chemistry, and magnetically guided precision.Magnetic Nanoparticles (MNPs), of which Superparamagnetic iron oxide nanoparticles (SPIONs) are the most clinically mature subclass, represent a class of cutting-edge theranostic platforms in that they simultaneously integrate drug delivery and AMF-hyperthermia alongside live MR imaging. Although SPIONs (magnetite/maghemite) are used as the base focus here, the performance of cobalt ferrites, permalloy alloys, and gadolinium-doped variants in context as the defining boundaries between material-specific design rules is presented here. Non-selective biodistribution and systemic toxicity plagued traditional pharmacotherapy, which SPIONs fundamentally countered through their favourable but context-dependent biocompatibility that requires careful evaluation of lysosomal iron release, ferroptotic risk, and route-dependent toxicity, tunable surface chemistry, and magnetically guided precision.&lt;/p&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;p&gt;This review strongly determines the translational landscape and mechanistics of nanomagnetic formulations across seven important disease areas such as oncology (lung, breast, prostate, and glioblastoma), Neurodegenerative (Alzheimer's disease, Parkinson's disease), pulmonary arterial hypertension, diabetes mellitus, tuberculosis, and asthma by using passive (EPR-mediated) and active targeting strategies, stimulus-responsive drug release paradigms, blood–brain barrier penetration mechanisms.&lt;/p&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;p&gt;This narrative review summarizes exemplary preclinical formulation candidates and registered clinical trials conducted for the proposed seven areas for the purpose of creating conceptual designs that include the CE-marked EU medical device NanoTherm® for glioblastoma thermotherapy.&lt;/p&gt;&lt;h3&gt;Result&lt;/h3&gt;&lt;p&gt;A novel unified magnetic nanoformulation design logic tree is demonstrated, providing ideas related to formulation selection around an anatomical barrier–route–stimulus triad, and it argues for a conceptual complexity-translatability heuristic: where clinically successful systems seem to be ones with simpler formulations. AMF-b","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}