Molecular Pharmaceutics最新文献

{"title":"Auger Electron Therapy Enhanced by Heat-Triggered Release of I-125-Labeled DNA-Targeted Compounds within the Tumor Microenvironment","authors":"Masayuki Munekane,&nbsp;Kazuki Matsunaga,&nbsp;Miki Ozaki,&nbsp;Hiroaki Echigo,&nbsp;Kenji Mishiro,&nbsp;Takeshi Fuchigami,&nbsp;Kazuma Ogawa","doi":"10.1021/acs.molpharmaceut.6c00443","DOIUrl":"10.1021/acs.molpharmaceut.6c00443","url":null,"abstract":"<p>In Auger electron therapy, the effective delivery ofAuger electron-emittingradionuclides to the nuclei of cancer cells is essential for achievinghigh therapeutic efficacy. In this study, we developed a novel strategythat combined thermosensitive liposomes (TSLs) encapsulating ¹²⁵I-labeled DNA-targeted compounds. This approach enabledenhanced tumor accumulation via TSL-mediated delivery and efficientnuclear translocation of radioactivity by releasing an ¹²⁵I-labeled doxorubicin derivative ([¹²⁵I]I-DOX) withinthe tumor microenvironment. [¹²⁵I]I-DOX exhibited highcellular and nuclear uptake, producing potent cytotoxicity throughAuger electrons emitted from ¹²⁵I. [¹²⁵I]I-DOX-loadedTSLs efficiently released [¹²⁵I]I-DOX at 43 °C, enhancingits cellular uptake by Colon-26 cells. Tumor accumulation of radioactivityin the heating group was much higher than in the nonheating group,and the accumulation was maintained for up to 48 h postinjection.Intravenous injection of [¹²⁵I]I-DOX-loaded TSLs (5.0 MBq)and localized tumor heating significantly inhibited tumor growth withoutbody weight loss. The combination of [¹²⁵I]I-DOX-loadedTSLs and hyperthermia represents a promising strategy for Auger electrontherapy targeting the nuclei of cancer cells.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"23 9","pages":"4681–4689"},"PeriodicalIF":4.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the LSER Approach in the Era of Machine Learning: Insights from IAM Chromatography","authors":"Wiktor Nisterenko,&nbsp;Katarzyna Ewa Greber,&nbsp;Magdalena Kierkowicz,&nbsp;Krzesimir Ciura","doi":"10.1021/acs.molpharmaceut.6c00381","DOIUrl":"10.1021/acs.molpharmaceut.6c00381","url":null,"abstract":"<p>The present study demonstrates the integration of thelinear solvationenergy relationship (LSER) concept with machine learning (ML) methodologiesto improve the predictive and interpretative capabilities of chromatographicretention modeling. Immobilized artificial membrane (IAM) chromatographywas employed as a model biochromatographic system, and an in-houselibrary of 993 structurally diverse compounds, with experimentallydetermined chromatographic hydrophobicity index of IAM (CHI_IAM), was used to train LSER-ML models. LSER descriptors were calculatedusing Absolv and extended with ionization-state descriptors to evaluatethe applicability of the LSER framework for realistic in silico virtualscreening scenarios. Several regression algorithms were tested, includinglinear, neighborhood-based, kernel-based, and ensemble tree-basedmodels. Among them, the support vector regression with the radialbasis function kernel (SVR-RBF) demonstrated the most balanced performanceacross all validation metrics of <em>R</em>²_train = 0.884, <em>R</em>²_test = 0.853, and <em>Q</em>²_cv = 0.811,achieving predictive errors (RMSE_train = 5.546, RMSE_test = 4.609, and RMSE_cv = 6.989) close to the analyticaluncertainty. Model interpretability was achieved using SHapley AdditiveexPlanations (SHAP), which confirmed the mechanistic relevance ofthe Abraham descriptors and the dominant contribution of hydrophobicvolume and hydrogen-bonding properties to IAM retention. Applicabilitydomain was verified with a Williams plot (±3 standardized residualsand leverage threshold <em>h*</em>). The results indicatethat the proposed LSER-ML approach provides an interpretable, robust,and generalizable tool for modeling membrane-mimetic chromatographicsystems and can be effectively applied in virtual screening and property-basedmolecular design.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"23 9","pages":"4647–4655"},"PeriodicalIF":4.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voices in Molecular Pharmaceutics: Meet Dr. Paul Klauser, Who Is Developing the Next Generation of Radiotheranostic Drugs to Improve Cancer Therapy","authors":"Paul C. Klauser","doi":"10.1021/acs.molpharmaceut.6c00657","DOIUrl":"10.1021/acs.molpharmaceut.6c00657","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"23 9","pages":"4390–4391"},"PeriodicalIF":4.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147979747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered Natural Killer Cell Derived-Extracellular Vesicles: An Acellular Immunotherapy with Cytotoxic Effects in SNU-1079 Human Cholangiocarcinoma Cells","authors":"Piyush Gondaliya,&nbsp;Dylan A. Zinn,&nbsp;Adil Ali Sayyed,&nbsp;Julia Driscoll,&nbsp;Irene K. Yan,&nbsp;Nadia Mensali,&nbsp;Sébastien Wälchli,&nbsp;Tushar Patel","doi":"10.1021/acs.molpharmaceut.6c00219","DOIUrl":"10.1021/acs.molpharmaceut.6c00219","url":null,"abstract":"<p>The use of natural killer (NK) cells for the treatmentof solidtumors such as cholangiocarcinoma has been hindered by challengesrelated to cell production, persistence and trafficking, as well asby reduced efficacy within an immunosuppressive tumor microenvironment.Antitumor immunity can be reduced by the interaction of NK cell expressedprogrammed cell death protein 1 (PD1) with ligands on tumor and othercells within the tumor microenvironment. The antitumor effect of NKcells is enhanced in cells engineered to express a truncated PD1 withoutan intracellular domain. The cytolytic potential and therapeutic efficacyof extracellular vesicles (EVs) derived from human NK cells expressingtruncated PD1 was evaluated as a cell-free therapeutic to overcomesome limitations faced by cell therapies. We demonstrate the feasibilityof efficient expansion, production and isolation of therapeutic vesiclesfrom human NK cell lines and from engineered NK92 cells expressingtruncated PD1. The cytotoxic efficacy of these therapeutic vesicleswas validated in both monolayer tumor cell cultures and in multicellulartumor spheroids. Concomitant administration of gemcitabine upregulatedNKG2D ligands on tumor cells and increased susceptibility to NK celland to NK cell derived EV mediated killing. These findings positionengineered NK cell derived-EVs as a scalable and promising cell-freeimmunotherapeutic for cholangiocarcinoma.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"23 9","pages":"4540–4552"},"PeriodicalIF":4.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Density Lipoprotein-Mimetic Nanoparticles Codelivering Self-Activated Cabazitaxel Prodrug and Verteporfin for Tumor Chemophotodynamic Therapy and Immune Activation","authors":"Mingli Wei,&nbsp;Chenxiao Chu,&nbsp;Huaiwei Ding,&nbsp;Jiansong Zhao,&nbsp;Muse Ji,&nbsp;Xinxin Liang,&nbsp;Xiaoshuang Bi,&nbsp;Jiaqi Zhao,&nbsp;Jingxin Gou,&nbsp;Tian Yin,&nbsp;Haibing He,&nbsp;Xing Tang,&nbsp;Yan Zhang,&nbsp;Yu Zhang","doi":"10.1021/acs.molpharmaceut.6c00317","DOIUrl":"10.1021/acs.molpharmaceut.6c00317","url":null,"abstract":"<p>Cabazitaxel (CTX) exhibits potent antineoplastic activityand isdemonstrated to promote antitumor immunity by triggering immunogeniccell death (ICD). This is commonly used in the clinical treatmentof advanced and metastatic triple-negative breast cancer (TNBC). However,the therapeutic index of commercial CTX injections is severely restrictedby their definite systemic toxicity and low tolerability. Herein,we developed biomimetic low-density lipoprotein nanoparticles (CTX₂TK&amp;VP@LDL NPs) by integrating ROS-responsive CTX dimericprodrugs (CTX₂TK) and the photosensitizer verteporfin (VP)into LDL NPs to selectively target tumors and achieve synergisticchemophotodynamic therapy and immunotherapy for TNBC with improvedbiosafety. CTX₂TK&amp;VP@LDL NPs were able to enhance theaccumulation and cellular uptake in 4T1 tumors overexpressing LDLreceptor, improving the targeted codelivery efficiency. When CTX₂TK&amp;VP@LDL NPs were deposited at the tumor sites, localized ¹O₂ was generated upon irradiation for triggeringultrafast CTX release with low premature CTX leakage in the off-targettissue. Additionally, the generated ¹O₂ canfurther synergistically reinforce ICD and elicit robust antitumorimmune activation. The combination treatment with CTX₂TK&amp;VP@LDLNPs and PD-L1 blockade notably inhibited abscopal tumor growth andlung metastasis. Taken together, the biomimetic CTX₂TK&amp;VP@LDLNPs exploit endogenous LDL functionality to enable receptor-mediatedtumor targeting and synergistic chemophotodynamic immune activation,providing an effective and safe therapeutic strategy for TNBC.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"23 9","pages":"4579–4595"},"PeriodicalIF":4.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing Nanoscale Features of Electrospun Amorphous Solid Dispersions Using Advanced Biophysical Analysis","authors":"Luyao Wang,&nbsp;Abhishek Rajbanshi,&nbsp;Najet Mahmoudi,&nbsp;Evangelia Tsolaki,&nbsp;Thomas Zillhardt,&nbsp;Eleanor Hilton,&nbsp;Michael T. Cook,&nbsp;Gareth R. Williams","doi":"10.1021/acs.molpharmaceut.6c00342","DOIUrl":"10.1021/acs.molpharmaceut.6c00342","url":null,"abstract":"<p>Amorphous solid dispersions(ASDs) can significantly enhance thesolubility of poorly soluble active pharmaceutical ingredients (APIs).However, the typical thermodynamic instability of ASDs is a significantbarrier to commercial success, and understanding API recrystallizationbehavior is crucial for enhancing stability. While most techniquesdo not allow the effective exploration of early-stage crystallization,small-angle neutron scattering (SANS) has shown promise in the studyof nanoscale drug domains in polymer–drug composite materials.In this study, aspirin was incorporated in electrospun polycaprolactone(PCL) fibers at loadings from 10–30% w/w. Electron microscopyrevealed the fibers to have smooth surfaces and diameters of 2–3μm. X-ray diffraction and differential scanning calorimetryrevealed the presence of crystalline drug at 20 and 30% loadings.Infrared spectroscopy indicated the presence of intermolecular interactionsbetween the drug and the polymer; however, these interactions wereinsufficient to completely inhibit drug crystallization when the drugwas supersaturated. SANS revealed heterogeneous nanoscale structureswithin the fibers, characterized by concentration-dependent drug-richdomains in the polymeric matrix. Their precise solid-state nature(amorphous versus crystalline) could not be determined by SANS, thoughX-ray diffraction indicated the presence of crystalline material athigher drug loadings. The SANS data also indicated the growth of drugaggregates after exposure to water. In vitro drug release tests suggestedthat the size of the drug domains could influence drug release behavior.Overall, this study provides a number of new insights into the crystallizationof APIs in electrospun ASDs, which can be used to help guide the futuredevelopment of more effective medicines.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"23 9","pages":"4596–4610"},"PeriodicalIF":4.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organic Anion/Cation Transporters: From Molecular Insights to Clinical Impact and Nanotechnology Innovation","authors":"Qi Guo,&nbsp;Xingru Long,&nbsp;Dawei Jiang,&nbsp;Huanhuan Liu","doi":"10.1021/acs.molpharmaceut.6c00480","DOIUrl":"10.1021/acs.molpharmaceut.6c00480","url":null,"abstract":"<p>Organic anion and cation transporters (OATs and OCTs),membersof the solute carriers (SLC)22 family, are critically involved inthe transport of endogenous metabolites and xenobiotics across keybarriers in the kidney, liver, and choroid plexus. While their rolein small-molecule drug pharmacokinetics, drug–drug interactions,and clinical issues is well established, their potential interactionwith nanomaterials remains a largely unexplored frontier. This isparticularly significant given that the long-term retention of nanomaterialsin vivo poses a major challenge to their clinical translation. Wehypothesize that OATs and OCTs recognize specific nanomaterials assubstrates, thereby mediating a novel and active elimination pathwaythat transcends conventional size-dependent filtration. This reviewsystematically delineates the structural and functional basis of majorOAT/OCT subtypes (e.g., OAT1–3, URAT1, OCT1–3) to establisha conceptual framework and then integrates this with current clinicalapplications and a brief discussion on the primary biological eliminationroutes of nanomaterials. By bridging these fields, this review aimsto prompt a paradigm shift in nanomedicine design, advocating forthe rational engineering of nanomaterial properties (e.g., size, charge,surface, shape) to engage with these transport systems. Ultimately,leveraging OAT/OCT pathways may unlock novel strategies to preciselycontrol nanomedicine distribution and enhance clearance, thereby acceleratingsafe and effective clinical translation.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"23 9","pages":"4416–4440"},"PeriodicalIF":4.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Serum Albumin Binding with Cotarnine Derivatives and Its Hemostatic, Wound-Healing, and Antibacterial Activities: Experimental and Molecular Docking Studies","authors":"Laxmipriya Prusty,&nbsp;Smrutimayee Panda,&nbsp;Seekha Naik,&nbsp;Samadrita Roy,&nbsp;Pradyota Kumar Behera,&nbsp;Laxmidhar Rout,&nbsp;Devendra Verma,&nbsp;Monalisa Mishra,&nbsp;Harekrushna Sahoo","doi":"10.1021/acs.molpharmaceut.6c00186","DOIUrl":"10.1021/acs.molpharmaceut.6c00186","url":null,"abstract":"<p>Human serum albumin (HSA) plays a key role in regulatingthe transportand bioavailability of therapeutic molecules, making protein–ligandinteraction studies essential for assessing biomedical compatibility.In this work, the interaction of cotarnine and its derivatives withHSA was systematically investigated using spectroscopic, thermodynamic,and molecular docking approaches, along with evaluation of antibacterial,wound healing, and hemostatic activities. Spectroscopic analyses confirmedefficient binding of the derivatives to HSA without disrupting itsnative secondary structure, while thermodynamic studies revealed spontaneous,enthalpy-driven interactions dominated by noncovalent forces. Dockingstudies identified favorable binding orientations within HSA bindingpockets, complementing the experimental results. All derivatives ofcotarnine show greater binding and biological activity, such as woundhealing and hemostatic, than cotarnine. Among the derivatives, L2exhibited the strongest binding affinity and superior biological performance,which can be attributed to enhanced hydrophobic interactions arisingfrom its chloro-substituted aromatic moiety. Overall, the combinedbiophysical, computational, and biological findings highlight cotarninederivatives, particularly L2, as promising multifunctional candidatesfor wound-healing and related biomedical applications.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"23 9","pages":"4524–4539"},"PeriodicalIF":4.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unnatural Amino Acid Substitutions to Improve In Vivo GRPR-Targeting Capability of [68Ga]Ga-SP01011 for Cancer Imaging","authors":"Sheetal Pathania,&nbsp;Chao-Cheng Chen,&nbsp;Pauline Ng,&nbsp;Helen Merkens,&nbsp;Wing Sum Lau,&nbsp;Joseph Lau,&nbsp;François Bénard,&nbsp;Kuo-Shyan Lin","doi":"10.1021/acs.molpharmaceut.6c00854","DOIUrl":"10.1021/acs.molpharmaceut.6c00854","url":null,"abstract":"&lt;p&gt;Gastrin-releasing peptide receptor (GRPR) shows elevatedexpressionin several malignancies and represents an attractive target in cancerimaging and radioligand therapy. However, improving in vivo stabilitywithout compromising high tumor uptake and low pancreatic uptake remainsa key challenge for the development of GRPR-targeted radiopharmaceuticals.In the present study, we investigated whether incorporating unnaturalamino acid substitutions at potential cleavage sites of the previouslyreported GRPR-targeted agonist [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-SP01011 (Ga-DOTA-Pip-&lt;span&gt;d&lt;/span&gt;-Phe-Gln&lt;sup&gt;7&lt;/sup&gt;-Trp&lt;sup&gt;8&lt;/sup&gt;-Ala&lt;sup&gt;9&lt;/sup&gt;-Val&lt;sup&gt;10&lt;/sup&gt;-Gly&lt;sup&gt;11&lt;/sup&gt;-His&lt;sup&gt;12&lt;/sup&gt;-Leu&lt;sup&gt;13&lt;/sup&gt;-Ac6c&lt;sup&gt;14&lt;/sup&gt;-NH&lt;sub&gt;2&lt;/sub&gt;; Ac6c: 1-amino-1-cyclohexanecarboxylic acid)could enhance in vivo stability without compromising tumor-targetingcapability. SP01012, SP01013, and SP01019 incorporating NMe-His&lt;sup&gt;12&lt;/sup&gt;, Ala(&lt;em&gt;t&lt;/em&gt;Bu)&lt;sup&gt;13&lt;/sup&gt; and Tle&lt;sup&gt;10&lt;/sup&gt;/NMe-His&lt;sup&gt;12&lt;/sup&gt; substitutions, respectively, were synthesizedby Fmoc solid-phase peptide synthesis and obtained in 22–60%yield. Their corresponding nonradioactive Ga complexes were obtainedin 58–89% yield by reacting the DOTA-conjugated precursorswith excess GaCl&lt;sub&gt;3&lt;/sub&gt; in acetate buffer, and the products weresubsequently purified by HPLC. In vitro competition binding assaysdemonstrated that the K&lt;sub&gt;i&lt;/sub&gt; values of Ga-SP01012, Ga-SP01013and Ga-SP01019 were 1.36 ± 0.12, 11.5 ± 0.89 and 2.29 ±0.77 nM, respectively. All three ligands retained agonistic characteristicsas confirmed by the calcium release assay. Their &lt;sup&gt;68&lt;/sup&gt;Ga-labeledanalogs were obtained by reacting the precursors with [&lt;sup&gt;68&lt;/sup&gt;Ga]GaCl&lt;sub&gt;3&lt;/sub&gt; in HEPES buffer with microwave heating (100 °C,1 min). Following HPLC purification, &lt;sup&gt;68&lt;/sup&gt;Ga-labeled tracerswere obtained in 33–47% decay-corrected radiochemical yieldwith radiochemical purities &gt;95%. PET/CT imaging together withexvivo biodistribution analyses conducted at 1 h postinjection in PC-3tumor-bearing mice demonstrated clear tumor visualization and predominantlyrenal excretion for all three tracers. Among them, [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-SP01012containing the NMe-His&lt;sup&gt;12&lt;/sup&gt; substitution alone, had the mostfavorable profile, with the highest tumor uptake (15.8 ± 0.65%ID/g), low pancreas uptake (1.27 ± 0.32% ID/g), and improvedin vivo plasma stability (78.1 ± 0.83% intact tracer at 15 minpostinjection compared to 63.5 ± 6.24% for [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-SP01011).In contrast, [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-SP01019, containing both Tle&lt;sup&gt;10&lt;/sup&gt; and NMe-His&lt;sup&gt;12&lt;/sup&gt; substitutions, showed the highestplasma stability (88.3 ± 2.90% intact tracer at 15 min postinjection),but this was accompanied by lower tumor uptake (12.4 ± 1.54%ID/g) and markedly increased pancreas uptake (23.7 ± 3.47% ID/g).[&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-SP01013, containing the Ala(&lt;em&gt;t&lt;/em&gt;Bu)&lt;sup&gt;13&lt;/sup&gt; substitution, showed reduced GRPR binding affinityand lower tumor uptake (8.33 ± 1.41% ID/g)","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"23 9","pages":"4770–4781"},"PeriodicalIF":4.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insight into the Development of Desirable Dosage Forms and Bioenabling Strategies to Improve the Food Effect of Anticancer Drugs for the Pediatric Population","authors":"Abhijeet Upadhye,&nbsp;Murali Monohar Pandey","doi":"10.1021/acs.molpharmaceut.5c00642","DOIUrl":"10.1021/acs.molpharmaceut.5c00642","url":null,"abstract":"<p>The design and development of suitable dosage forms forpediatricpatients face myriad challenges. Compared to other dosage forms, oraldosage forms are widely used and accepted in pediatric patients. However,oral dosage forms have their own challenges, which include the requirementfor dose flexibility, limited bioavailability due to the poor solubilityof the drug, safety concerns regarding excipients, and drug administrationchallenges for pediatric patients. The importance of research in drugdelivery of anticancer drugs has increased due to poor drug solubilityand the limited availability of pharmacokinetic data in pediatricpatients. The poor solubility of anticancer drugs necessitates higherdoses, leading to increased episodes of adverse effects. Furthermore,administering these drugs in the fed state results in bioavailabilityvariations compared to the fasting state, which becomes more criticalfor pediatric patients. Therefore, it is essential to screen formulationstrategies for these drugs to improve their bioavailability in theearly stages of development. This review outlines key concerns ofpediatric patients receiving long-term cancer drug therapy, includingphysiological and pharmacological challenges in the pediatric population,the impact of food on drug efficacy, and potential adverse effectsassociated with it. It also highlights various formulation strategiesaimed at mitigating food-related variability through bioavailabilityenhancement. Furthermore, the review addresses the safety levels ofexcipients and development of age-appropriate dosage forms for thepediatric population.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"23 9","pages":"4394–4415"},"PeriodicalIF":4.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}