MOLECULAR PHARMACEUTICS分子药剂学
MOLECULAR PHARMACEUTICS(英文缩写 MOL PHARMACEUT),ISSN 1543-8384,eISSN 1543-8392,中文译名:分子药剂学 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-27 至 2026-09-27，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 5.364 | Q1 |
| 2022 | 4.900 | Q1 |
| 2023 | 4.500 | Q1 |
| 2024 | 4.500 | Q1 |
| 2025 | 4.900 | Q1 |
MOLECULAR PHARMACEUTICS 最新收录文献
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1. Retraction of "Induced Disorder in Protein-Ligand Complexes as a Drug-Design Strategy".
PMID:日期:2026-09-07该文献暂无摘要。
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2. Pure but Not Simple: Supersaturation from Excipient-Free, Vapor-Generated, Amorphous Griseofulvin Nanoparticles.
PMID:日期:2026-09-07Rapid crystallization of an active pharmaceutical ingredient can suppress its observable supersaturation and negate this potential advantage of the amorphous form. Excipients added to formulations can prolong supersaturation, but reduce drug loading and obscure the intrinsic dissolution behavior of the drug in testing. Here, we describe spring-and-parachute dissolution behavior in fasted-state simulated intestinal fluid of an archetypal poorly soluble and strongly crystallizing drug, griseofulvin (GSF), in the form of excipient-free, pure, amorphous nanopowders generated using a novel, single-step, solvent-free technique of organic vapor jet desublimation. Using experiments and modeling, we establish how initial dissolution rate, peak concentration, and area under the concentration-time curve scale with dose, distinguishing between dose regimes in which supersaturation behavior is monotonic and nonmonotonic. The roles of local surface crystallization, particle aggregation, and nonequilibrium crystallization at high supersaturation are elucidated, providing a framework for attaining excipient-free supersaturation and guiding the development of improved dissolution models.
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3. Insight into the Development of Desirable Dosage Forms and Bioenabling Strategies to Improve the Food Effect of Anticancer Drugs for the Pediatric Population.
PMID:日期:2026-09-07The design and development of suitable dosage forms for pediatric patients face myriad challenges. Compared to other dosage forms, oral dosage forms are widely used and accepted in pediatric patients. However, oral dosage forms have their own challenges, which include the requirement for dose flexibility, limited bioavailability due to the poor solubility of the drug, safety concerns regarding excipients, and drug administration challenges for pediatric patients. The importance of research in drug delivery of anticancer drugs has increased due to poor drug solubility and the limited availability of pharmacokinetic data in pediatric patients. The poor solubility of anticancer drugs necessitates higher doses, leading to increased episodes of adverse effects. Furthermore, administering these drugs in the fed state results in bioavailability variations compared to the fasting state, which becomes more critical for pediatric patients. Therefore, it is essential to screen formulation strategies for these drugs to improve their bioavailability in the early stages of development. This review outlines key concerns of pediatric patients receiving long-term cancer drug therapy, including physiological and pharmacological challenges in the pediatric population, the impact of food on drug efficacy, and potential adverse effects associated with it. It also highlights various formulation strategies aimed at mitigating food-related variability through bioavailability enhancement. Furthermore, the review addresses the safety levels of excipients and development of age-appropriate dosage forms for the pediatric population.
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4. Systematic Investigation on Particle and Pore Size Effects of Mesoporous Silica on Molecular Mobility and Physical Stability of Overloaded Amorphous Acetaminophen.
PMID:日期:2026-09-07Polymeric excipients are generally used for physical stabilization of amorphous drugs. However, a more strategic design of amorphous formulations is needed to reduce the amount of excipients, for which the use of mesoporous materials can be a promising option. In this study, mesoporous silica (MS) with various particle and pore sizes were added to amorphous acetaminophen (AAP) at various mixing ratios to systematically clarify their stabilization mechanisms. In particular, how the presence of MS affects the stability, at mixing ratios where AAP is present in excess relative to the pore volume, was focused. Six types of MS, with pore and particle sizes ranging from 2.5 to 21 nm and from 3 to 9 μm, respectively, were used in the study. Differential scanning calorimetry (DSC) analysis suggested the presence of three molecular fractions of amorphous AAP with different molecular mobilities: free, intermediate, and rigid fractions. The free fraction behaved similarly to pure AAP, whereas the intermediate fraction appeared to be relatively more stable. The rigid fraction had limited molecular mobility and was expected to strongly interact with the MS surface. AAP molecules mainly existed as the free fraction in the presence of 10% MS, regardless of the MS type. The free fraction disappeared to allow domination by the intermediate fraction with 50% MS having 17 or 21 nm pores, whereas a significant amount of the free fraction remained with MS having 2.5 nm pores. Broadband dielectric spectroscopy (BDS) analysis revealed that the addition of MS both increased and decreased the molecular mobility of amorphous AAP. The presence of all types of 10% MS slightly accelerated the γ-relaxation of amorphous AAP without affecting the α-relaxation. The addition of 50% MS with 17 or 21 nm pores slowed down the a-relaxation time of amorphous AAP, whereas the effect was marginal for MS with 2.5 nm pores. Isothermal crystallization of amorphous AAP at 60 °C was accelerated in the presence of MS with 2.5 nm pores at mixing ratios of both 10 and 50%. In contrast, 50% MS with 17 or 21 nm pores exhibited a strong stabilization effect. The accelerated crystallization in the presence of MS with 2.5 nm pores was explained by an increase in local molecular mobility. Mixtures with MS with 17 or 21 nm pores exhibited higher stability, which was explained by the large portion of the intermediate fraction with slower motion relative to that of pure AAP. The intermediate fraction was assumed to move inside and outside the pores, and the ease of molecular exchange was explained by the size of the pores and characteristic length of the cooperatively rearranging region of amorphous AAP. These observations provide guidance for the selection of MS materials for the stabilization of large amounts of pharmaceutical glasses and the scientific significance of the molecular dynamics of glasses in the presence of porous materials.
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5. The Road toward a Trojan Horse Malaria Vaccine: Chemical Augmentation of Live Sporozoites without Affecting Their Viability.
PMID:日期:2026-09-07In our effort to design an effective ultralow-dose attenuated whole sporozoite (SPZ) vaccine, we explored the use of chemical adjuvants to increase the immunogenicity of sporozoites. Critical to the potency of attenuated sporozoites is their ability to migrate to and infect the liver. We thus used an in vivo mouse challenge model to compare the effects of external and internal chemical modifications to sporozoites. We loaded sporozoites with CL307 using two strategies: a supramolecular surface modification adjuvant system (SPZ-SAS(CL307)) and a mitochondrial membrane potential system (SPZ-MMP(CL307)). SPZ-SAS(CL307) contained 200 times more CL307 as compared to SPZ-MMP(CL307). However, SPZ-SAS(CL307) could not establish a liver infection after intravenous injection (25 000 sporozoites), suggesting loss of function of the sporozoites. On the contrary, SPZ-MMP(CL307) could establish an equivalent liver infection to the control already at a dose of 5000 sporozoites. When the immunized mice were challenged, SPZ-MMP(CL307) equaled the protective efficacy of control sporozoites. Our findings indicate that the MMP system can be used to chemically augment live cells, such as sporozoites, with adjuvants without negatively affecting their infectivity and protective efficacy in vivo. For malaria, further testing of different types of adjuvants at different concentrations is needed to ultimately develop vaccines with increased potency. However, in essence, this platform provides a proof-of-concept for a Trojan horse adjuvanting or drug loading concept for any whole-cell vaccine or therapy, within the infectious diseases space or beyond in oncological applications.
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6. Targeted Delivery of Carvacrol via TPGS-Tf-Polydopamine Nanoconjugate Scaffold on TNBC Tumor Xenograft for Understanding In Vivo Tumor Dynamics and 3D Cancer Spheroid Model, Mimicking a Tumor Environment.
PMID:日期:2026-09-07The high expression of transferrin receptors on the surface of cancer cells makes them a potential target for drug internalization, which has become a golden opportunity in targeted cancer therapy. Carvacrol, a naturally occurring phenolic compound present in essential oils, has attracted considerable attention for its pronounced anticancer activity against diverse human malignancies. Nevertheless, its therapeutic application in vivo is constrained by intrinsic physicochemical and pharmacokinetic limitations, including poor water solubility, suboptimal bioavailability, and rapid systemic elimination. To address these challenges, the present study highlights the fabrication of transferrin-targeted TPGS-conjugated carvacrol (CVC)-loaded polydopamine nanoparticles (CVC-PDA-TPGS-Tf NPs), with exploration of the antitumor efficacy of nanocarrier-mediated carvacrol, deploying a murine triple-negative breast cancer (TNBC) tumor xenograft model and a human TNBC three-dimensional (3D) spheroid model, as 3D cell culture technologies more thoroughly bear a resemblance to in vivo cell environments to accommodate improved precision in drug discovery. This work demonstrates the successful creation of nanoconjugate CVC-PDA-TPGS-Tf NPs (∼112 nm in size) and their thorough physicochemical characterization after synthesis. Intraperitoneal administration of CVC-PDA-TPGS-Tf NPs substantially inhibited tumor growth in the 4T1 xenograft model. Carvacrol effectively disintegrates MDA-MB-231 spheroids, illustrating a proportionately higher uptake of carvacrol nanoconjugates by these spheroids. The molecular docking studies also pinpointed the interaction of potential cancer biotargets with carvacrol in estrogen- and progesterone-receptor-positive breast cancer cells, in addition to its mentioned therapeutic efficiency against TNBC. In conclusion, these findings support CVC-PDA-TPGS-Tf as a promising platform for TNBC and potentially hormone receptor-positive breast cancers, warranting further mechanistic and translational studies.
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7. Evaluation of 18F-FPPA as a Positron Emission Tomography Radioligand for Imaging CSF1R in LPS-Induced Rat Model of Neuroinflammation.
PMID:日期:2026-09-07Noninvasive detection of microglia is crucial for monitoring their spatiotemporal dynamics and facilitating early medical intervention during the prodromal stages of these neuroinflammatory diseases. Colony-stimulating factor 1 receptor (CSF1R) is a promising imaging biomarker for microglia in neuroinflammation. However, currently developed CSF1R-targeted probes lack [18F]-labeled variants, and their stability, sensitivity, and specificity are all suboptimal to some extent. In our study, based on pyrrolopyrimidines(a distinct structure of CSF1R inhibitors), we developed the [18F]-labeled CSF1R-targeted probe-18F-FPPA (6-(4-(2-(2-(2-(fluoro-18F)ethoxy)ethoxy)ethoxy)phenyl)-N-methyl-N-(3-methylbenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine).18F-FPPA was synthesized with a radiochemical yield of 4-7%, molar activity of 30-70 GBq/μmol, and radiochemical purity exceeding 99%, which possesses excellent physicochemical properties, rapid blood pharmacokinetics (T1/2α = 2.50 min, T1/2β = 32.4 min), favorable invitro and in vivo stability, and a clear metabolic pathway via dual hepatobiliary and renal excretion. A marked uptake of 18F-FPPA was observed at the LPS injection site in the LPS group at 30-40 min postinjection. A decreased uptake also was observed in cold 19F-FPPA, BLZ945, and PLX3397 blocking groups (P < 0.05), and no obvious increase in the group of intraperitoneal injection of cyclosporine A (P > 0.05). The in vivo imaging and immunohistochemical results confirmed the specific uptake of 18F-FPPA by targeting CSF1R on microglia in inflamed tissues. Overall, our findings demonstrated that 18F-FPPA had great potential as a promising tracer for the imaging of neuroinflammatory diseases, while its unique binding profile also provides insights into CSF1R-targeted ligand development.
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8. Engineered Natural Killer Cell Derived-Extracellular Vesicles: An Acellular Immunotherapy with Cytotoxic Effects in SNU-1079 Human Cholangiocarcinoma Cells.
8. 工程化自然杀伤细胞衍生的细胞外囊泡：一种在SNU-1079人胆管癌细胞中具有细胞毒性作用的脱细胞免疫疗法PMID:日期:2026-09-07The use of natural killer (NK) cells for the treatment of solid tumors such as cholangiocarcinoma has been hindered by challenges related to cell production, persistence and trafficking, as well as by reduced efficacy within an immunosuppressive tumor microenvironment. Antitumor immunity can be reduced by the interaction of NK cell expressed programmed cell death protein 1 (PD1) with ligands on tumor and other cells within the tumor microenvironment. The antitumor effect of NK cells is enhanced in cells engineered to express a truncated PD1 without an intracellular domain. The cytolytic potential and therapeutic efficacy of extracellular vesicles (EVs) derived from human NK cells expressing truncated PD1 was evaluated as a cell-free therapeutic to overcome some limitations faced by cell therapies. We demonstrate the feasibility of efficient expansion, production and isolation of therapeutic vesicles from human NK cell lines and from engineered NK92 cells expressing truncated PD1. The cytotoxic efficacy of these therapeutic vesicles was validated in both monolayer tumor cell cultures and in multicellular tumor spheroids. Concomitant administration of gemcitabine upregulated NKG2D ligands on tumor cells and increased susceptibility to NK cell and to NK cell derived EV mediated killing. These findings position engineered NK cell derived-EVs as a scalable and promising cell-free immunotherapeutic for cholangiocarcinoma.
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9. Payload-Free [89Zr]Zr-DFO*-sq-Enfortumab ImmunoPET for Imaging Nectin-4 Expression in Bladder Cancer.
9. 无载荷[89Zr]Zr-DFO*-sq-Enfortumab免疫PET用于膀胱癌Nectin-4表达成像PMID:日期:2026-09-07Nectin-4-targeted imaging has emerged as a promising strategy for patient stratification in urothelial carcinoma, yet currently available radiotracers remain limited by rapid renal clearance, urinary background activity, or potential pharmacologic confounding associated with antibody-drug conjugate (ADC)-based constructs. To overcome some of these limitations, we developed a payload-free immunoPET radiotracer based on the native enfortumab antibody conjugated with the bifunctional chelator DFO*-sq and radiolabeled with zirconium-89 (89Zr). The resulting [89Zr]Zr-DFO*-sq-Enfortumab preserved Nectin-4-specific targeting while demonstrating high radiochemical stability in human serum (>99% through Day 12). In vitro studies showed efficient antigen-specific cellular internalization (80-85%), prolonged intracellular retention, and evidence consistent with partial recycling of antibody-associated species. In vivo, [89Zr]Zr-DFO*-sq-Enfortumab exhibited sustained tumor uptake reaching 17.4 ± 2.8% ID/g in high Nectin-4-expressing xenografts and correlated with differential Nectin-4 expression across multiple bladder cancer models. Importantly, the full-length antibody platform enabled high-contrast visualization of pulmonary metastatic lesions and orthotopic bladder tumors despite some urinary background activity. Together, these findings demonstrate that payload-free [89Zr]Zr-DFO*-sq-Enfortumab provides a biologically relevant immunoPET platform for noninvasive assessment of variable Nectin-4 expression and support its further evaluation as a companion imaging strategy for Enfortumab Vedotin-based therapies.
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10. Effect of Functional Groups Introduced into Radioiodinated Asymmetric Cyanine Dyes on Their In Vivo Behavior.
PMID:日期:2026-09-07After intravenous administration, some heptamethine cyanine dyes bind to serum albumin and accumulate in tumors via the enhanced permeability and retention effect. Additionally, asymmetric cyanine dyes have two indole moieties which allow conjugation of a low-molecular-weight anticancer agent to one of the N-substituent side chains. Therefore, asymmetric heptamethine cyanine dyes have been studied as possible platforms for tumor-targeted drug delivery. However, the effects of functional groups on the opposite side chains on their in vivo behavior have not been explored in detail. Therefore, in this study, we aimed to clarify these effects by designing three model asymmetric cyanine dyes. For each dye, the side chain opposite the drug-conjugation site was modified with either an alkyl chain, a carboxyl group, or a sulfonyl group. A 125I atom was introduced on the other side of the molecule to enable quantitative biodistribution analysis. The resulting compounds are referred to as [125I]Bu, [125I]COOH, and [125I]SO3H. The albumin binding affinities (Kb values) for the corresponding nonradioactive compounds, Bu, COOH, and SO3H, were 0.82, 1.17, and 1.18 × 106 L/mol, respectively. In biodistribution studies, [125I]COOH showed higher radioactivity in the blood and tumors than [125I]Bu, whereas [125I]SO3H showed lower radioactivity levels. Notably, these differences did not correlate with their Kb values. Fluorescence analyses of the compounds incubated in serum-containing medium demonstrated that the fluorescence of COOH and Bu plateaued after approximately 1 and 2 h, respectively, whereas that of SO3H continued to change beyond 3 h, consistent with a slower time-dependent change in the protein-associated state of SO3H. Moreover, longer preincubation times of the radiolabeled asymmetric cyanine dyes in serum-containing medium decreased their transfer from the medium to the cellular side, with the greatest decrease observed for [125I]COOH. These results suggest that functional groups affect albumin-binding affinity, serum protein-associated states, and subsequent transfer to the cellular side, thereby influencing blood retention and tumor accumulation. Our findings provide a basis for the rational optimization of asymmetric cyanine dyes by modulating albumin interactions that influence their in vivo behavior.