Journal of pharmaceutical sciences最新文献

Self-assembled polymeric prodrug provides controlled cisplatin release and enhanced efficiency in local chemotherapy. 自组装聚合前药可控制顺铂释放，提高局部化疗效率。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-05-06 DOI: 10.1016/j.xphs.2026.104317

Mohamed M Abdelghafour, Bence Kutus, László Mérai, Miklós Csanády, Nikoletta Szemerédi, Gabriella Spengler, Diána Szabó, László Rovó, László Janovák

{"title":"Self-assembled polymeric prodrug provides controlled cisplatin release and enhanced efficiency in local chemotherapy.","authors":"Mohamed M Abdelghafour, Bence Kutus, László Mérai, Miklós Csanády, Nikoletta Szemerédi, Gabriella Spengler, Diána Szabó, László Rovó, László Janovák","doi":"10.1016/j.xphs.2026.104317","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104317","url":null,"abstract":"In this work, we report the synthesis of novel polymeric prodrug nanoparticles of cisplatin to reduce the severe side effects of cisplatin and investigate its potential localized delivery to aerodigestive tract carcinomas. Cisplatin was conjugated to succinylated poly(vinyl alcohol) (PVA-SA) via coordinate ester linkages. The abundance of residual hydroxyl (-OH) and carboxyl (-COOH) groups along the polymer backbone facilitated spontaneous nanoparticle self-assembly through ester bond crosslinking in a straightforward, one-pot reaction. Successful polymer modification and drug conjugation were confirmed using FTIR and EDX measurements. The in vitro cisplatin drug release studies were carried out over two weeks under physiological conditions (PBS, pH 7.4). The results showed that free cisplatin exhibited rapid release (k´=0.00829 h‒1), whereas the polymeric cisplatin prodrug demonstrated a significantly sustained release profile (k´=0.00046 h‒1), indicating its potential to reduce cisplatin-release side effects. Kinetic modelling of the release data revealed that the Korsmeyer-Peppas kinetic model provided the best fit, suggesting a combined diffusion- and erosion-controlled release mechanism. The anticancer activity of the polymeric cisplatin prodrug was evaluated using an MTT assay against two cancer cell lines (A549 and Hep-2). The polymeric cisplatin prodrug exhibited lower IC50 values (0.00122±0.00069 and 0.00079±0.00031 μM) compared to free cisplatin (0.00434±0.00134 and 0.00218±0.00074 μM) for A549 and Hep-2 lines, respectively. While limited to in vitro models and indirect mucoadhesion evidence, these findings suggest that the developed biocompatible system is a promising delivery platform for further evaluation in localized chemotherapy.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104317"},"PeriodicalIF":3.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Predicting surfactant effects on drug permeation across hollow fiber membrane. 预测表面活性剂对药物穿过中空纤维膜的影响。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-05-06 DOI: 10.1016/j.xphs.2026.104318

Roshni P Patel, Jack D Murray, Brendan T Griffin, James E Polli

{"title":"Predicting surfactant effects on drug permeation across hollow fiber membrane.","authors":"Roshni P Patel, Jack D Murray, Brendan T Griffin, James E Polli","doi":"10.1016/j.xphs.2026.104318","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104318","url":null,"abstract":"The hollow fiber membrane (HFM) system is a potential combined dissolution/permeation in vitro tool to predict oral solid dosage form performance. However, drug permeability interpretation in the presence of surfactants remains mechanistically challenging, particularly when surfactants are present in both the donor and receiver compartments. A model denoted the reduced resistance model was recently employed to explain enhanced drug permeability when surfactant was present in the receiver. The objective was to re-examine previously published HFM flux of griseofulvin and meloxicam to consider the reduced resistance model as an additional contributing mechanism impacting drug flux. Published HFM data under all four surfactant experimental scenarios (i.e., no surfactant, surfactant in the receiver only, surfactant in the donor only, and surfactant in both donor and receiver) were re-analyzed. For the latter two most complex scenarios, there were six competing permeation models. For these two scenarios, the best predictive model for griseofulvin was the reduced resistance model for total donor drug concentration; meanwhile, for meloxicam, which was much less micelle incorporated, the best predictive model was the simple free drug permeation model. Overall, these findings demonstrate that drug permeation across HFM in surfactant-containing systems is governed by the interplay between donor-side micellar sequestration and receiver-side resistance reduction.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104318"},"PeriodicalIF":3.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Supercooled liquid state facilitates recrystallization-mediated gelation of amorphous cinnarizine. 过冷的液态有利于非晶态肉桂碱的再结晶介导凝胶化。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-05-06 DOI: 10.1016/j.xphs.2026.104315

Yutong Li, Manlin Teng, Sining Han, Huijie Si, Rafel Prohens, Mingzhong Li, Qiang Fu

引用次数: 0

Dissolved oxygen effects on human growth hormone stability during freeze-thaw and metal-catalyzed oxidation. 溶解氧对冻融和金属催化氧化过程中人生长激素稳定性的影响。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-05-05 DOI: 10.1016/j.xphs.2026.104316

Yuya Miyahara, Ricarda Nagel, Wolfgang Friess

{"title":"Dissolved oxygen effects on human growth hormone stability during freeze-thaw and metal-catalyzed oxidation.","authors":"Yuya Miyahara, Ricarda Nagel, Wolfgang Friess","doi":"10.1016/j.xphs.2026.104316","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104316","url":null,"abstract":"Dissolved oxygen (DO) has been proposed to influence protein stability during freeze-thaw (F/T) processing, yet its direct impact remains unclear. This study evaluated whether DO levels or vacuum degassing affect the stability of human growth hormone (hGH) during F/T. Buffers were degassed with or without vacuum-induced surface freezing (VISF). Degassing itself did not induce particle formation. Upon freezing substantial aggregation occurred, independent of the presence or absence of dissolved gas. To isolate oxygen effects, hGH solutions equilibrated with nitrogen, air, or oxygen were subjected to F/T cycles or frozen storage at -40°C. DO levels did not significantly influence turbidity, particle counts, intact LC-MS profiles, while only minor differences were observed by SEC. Under metal-catalyzed oxidative conditions, however, oxygen modified aggregation pathways depending on the catalyst. These findings demonstrate that DO alone does not substantially affect hGH stability during F/T but becomes relevant in the presence of catalytic oxidative stress. Protein destabilization during freezing is instead dominated by interfacial stresses, particularly those associated with VISF. Together, these results help to distinguish chemical and physical contributions of dissolved gases in protein formulations.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104316"},"PeriodicalIF":3.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nano-enabled targeted transdermal therapy for pain management in cervical cancer. 纳米靶向经皮疗法治疗宫颈癌疼痛。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-05-04 DOI: 10.1016/j.xphs.2026.104313

Beatrice Odei-Mensah, Samson A Adeyemi, Lindokuhle M Ngema, Hillary Mndlovu, Yahya E Choonara

{"title":"Nano-enabled targeted transdermal therapy for pain management in cervical cancer.","authors":"Beatrice Odei-Mensah, Samson A Adeyemi, Lindokuhle M Ngema, Hillary Mndlovu, Yahya E Choonara","doi":"10.1016/j.xphs.2026.104313","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104313","url":null,"abstract":"Cervical cancer, caused by persistent infection with high-risk human papillomavirus (HPV) types, remains one of the leading causes of cancer death among women. Pain is a significant concern in patients with advanced disease, due to the anatomical position of cervical cancer as well as struggles with major therapeutic pain management remedies. Opioids, which are the mainstay of pain control, are saddled with many drawbacks, including poor tolerance, serious side effects, and addiction over long-term use. Transdermal delivery systems, including opioid patches, are established approaches for cancer pain management, offering sustained drug release and improved patient compliance. Nanocarriers, such as Lipid-, polymeric-, and inorganic-based nanocarriers, have been explored in recent years to improve the delivery of analgesics and anticancer drugs, offering a direct delivery to tumor cells, thereby reducing systemic exposure and limiting toxicity. These nanocarriers have demonstrated the ability to enhance drug penetration, modulate release profiles, and improve drug retention at sites associated with pain, leading to consistent analgesic effect and reduced systemic exposure. However, most evidence supporting these approaches remains at the preclinical level, with limited clinical data specifically addressing pain management in cervical cancer. This review examines the role of nano-enabled drug delivery systems, including transdermal and localized delivery systems in the management of cervical cancer and its associated pain. While nanotechnology offers a promising system for improving pain management strategies, further clinically relevant studies are required to establish its therapeutic value in the management of cervical cancer-associated pain.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104313"},"PeriodicalIF":3.8,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of pneumatic tube system transportation on product quality of therapeutic monoclonal antibody liquid drug products filled in vials and pre-filled syringes. 气动管道系统运输对小瓶和预充式注射器中治疗性单克隆抗体液药产品质量的影响。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-05-03 DOI: 10.1016/j.xphs.2026.104314

Kashappa Goud Desai, Cait Sofa, James D Colandene, Brendan Blockus, Ning Wang, Dina Elnabawi, Nathan Heacock, Bivash Mandal, Prachi Jirwankar

{"title":"Impact of pneumatic tube system transportation on product quality of therapeutic monoclonal antibody liquid drug products filled in vials and pre-filled syringes.","authors":"Kashappa Goud Desai, Cait Sofa, James D Colandene, Brendan Blockus, Ning Wang, Dina Elnabawi, Nathan Heacock, Bivash Mandal, Prachi Jirwankar","doi":"10.1016/j.xphs.2026.104314","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104314","url":null,"abstract":"Pneumatic tube systems (PTSs) offer rapid intra-hospital transport but may affect the quality of therapeutic monoclonal antibody (mAb) liquid drug products. This study demonstrates the impact of PTS transport on the product quality of two test mAb formulations (test mAb1 and mAb2), with or without stabilizing surfactants [0.04% w/v polysorbate 80 (PS80) or poloxamer 188 (P188)]. Formulations were filled into vials and prefilled syringes (PFSs) and transported for 878 m or 1,756 m using a novel laboratory-scale PTS. Formulations lacking surfactant contained visible particulates, and PTS transport exacerbated subvisible particle formation, resulting in 25-32-fold increases for vials and 2-3-fold increases for PFSs. Formulations containing 0.04% (w/v) PS80 or P188 were clear and essentially free of visible particulates and showed substantially lower (5-12-fold) increases in ≥2 µm subvisible particles after PTS transport. PFS samples exhibited higher subvisible particle counts than vials both before and after transport; this was attributed to silicone oil leaching from syringe barrels, which was exacerbated by PTS-induced stress. For PFSs formulated with 0.04% PS80, increases in subvisible particle counts were influenced by syringe air headspace and cumulative PTS stress: greater headspace and stress increased air-liquid interfacial effects (microbubbles and foaming) and subvisible particle formation. Other quality attributes were largely unaffected when surfactant was present. These findings provide critical data and practical guidance for developing safe and effective PTS transport strategies for therapeutic mAb liquid drug products in both vials and PFSs.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104314"},"PeriodicalIF":3.8,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A multi-dimensional modeling framework integrating metabolomics analysis and process modeling for bioprocess characterization. 一个多维建模框架整合代谢组学分析和过程建模的生物过程表征。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-05-02 DOI: 10.1016/j.xphs.2026.104306

Yingting Shi, Jingyu Jiao, Yuxiang Wan, Kerui Fang, Yuxia Jin, Jianyang Pan, Dong Gao, Haibin Wang, Haibin Qu

{"title":"A multi-dimensional modeling framework integrating metabolomics analysis and process modeling for bioprocess characterization.","authors":"Yingting Shi, Jingyu Jiao, Yuxiang Wan, Kerui Fang, Yuxia Jin, Jianyang Pan, Dong Gao, Haibin Wang, Haibin Qu","doi":"10.1016/j.xphs.2026.104306","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104306","url":null,"abstract":"Upstream bioprocess development relies heavily on design of experiment (DoE) and response surface methodology, which often focus on endpoint outcomes while overlooking the dynamic trajectories of cell culture processes. To overcome this limitation, this study established a multi-dimensional modeling framework integrating deterministic screening design (DSD), time-resolved metabolomics, and process modeling to elucidate how critical process parameters (CPPs) regulate antibody titer and quality attributes during the cell culture process. First, a DSD-based response surface model identified key regulators of antibody titer and quality. Subsequently, metabolomics analysis revealed the underlying metabolic mechanisms: higher temperature and inoculation density promoted amino acid and energy metabolism, whereas pH modulated central carbon flux. Building on these insights, Gaussian process regression (GPR) dynamic models were developed that integrate time-series metabolite profiles and CPPs to predict viable cell density and antibody titer with high accuracy (test-set R2 > 0.90). This model significantly outperformed conventional linear (PLS) and complex machine-learning approaches (boosted trees, neural networks). This work provides a coherent methodological pipeline for mechanistic understanding and real-time prediction of bioprocess, offering a valuable tool for robust bioprocess optimization and scale-up.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104306"},"PeriodicalIF":3.8,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and evaluation of sorafenib and curcumin co-loaded microemulsion gel for the management of breast cancer. 索拉非尼和姜黄素共载微乳凝胶治疗乳腺癌的开发与评价。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-05-02 DOI: 10.1016/j.xphs.2026.104310

Md Abul Barkat, Afaf F Almuqati, Harshita Barkat, Abdulkareem Ali Alanezi, Faisal Shwaikh Alanazi, Lokesh Kaushik, Mahesh Kumar Sharma, Kaisar Raza

{"title":"Development and evaluation of sorafenib and curcumin co-loaded microemulsion gel for the management of breast cancer.","authors":"Md Abul Barkat, Afaf F Almuqati, Harshita Barkat, Abdulkareem Ali Alanezi, Faisal Shwaikh Alanazi, Lokesh Kaushik, Mahesh Kumar Sharma, Kaisar Raza","doi":"10.1016/j.xphs.2026.104310","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104310","url":null,"abstract":"In this study, sorafenib (an established anticancer drug) and curcumin (a polyphenolic compound), both with numerous challenges like solubility, permeation, bioavailability, and dose-dependent toxicity, were co‑loaded in a microemulsion-based hydrogel for breast cancer management by the topical route. Based on the solubility studies, Capmul MCM was selected as the oil, and the surfactant mixture was selected as Labrasol and Tween‑80. A total of three pseudoternary phase diagrams were explored to select the optimum composition. Out of three studied compositions, the selected one exhibited a globule size of 100.7 ± 6.83 nm with a polydispersity index value of 0.239, zeta potential of -8.14 ± 1.61 mV, and pH of 5.7 ± 0.2. The developed Carbopol-based hydrogel offered shear‑thinning rheology with appreciable spreadability, higher drug content, and skin-compatible pH. MCF‑7 cell-based cytotoxicity studies not only established the substantial decrease in the IC₅₀ values for both sorafenib and curcumin when co‑delivered but also offered a combination index < 1, indicating synergism. Rodent skin permeation studies offered a higher release flux and drug retention for both the drugs vis-à-vis the conventional gel, and the dermatokinetics proved the skin delivery potential of the developed system with elevated Cmax, permeation rates, and AUC, and also slower elimination for sorafenib. The studies established the synergism of both drugs and provided a proof of concept for enhanced topical delivery with substantial in vitro anticancer effect that can be further explored in the in vivo models.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104310"},"PeriodicalIF":3.8,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New generations of electrospun Janus nanofibers for drug delivery. 用于药物输送的新一代电纺Janus纳米纤维。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-05-01 DOI: 10.1016/j.xphs.2026.104307

Deng-Guang Yu, Cui He, Jingjing Feng, Yanan Liu, Sim-Wan Annie Bligh

引用次数: 0

Investigating adeno-associated virus stabilization at the air-water interface through competitive adsorption. 通过竞争吸附研究腺相关病毒在空气-水界面的稳定性。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-05-01 DOI: 10.1016/j.xphs.2026.104304

Julie Garcia Gonzalez-Calero, Harri Rahn, Kan Wu, Josepha Roerig, Fabian Seebacher, Nikolai Hentze, Markus Hollmann, Dirk Grimm, Chen Zhou

{"title":"Investigating adeno-associated virus stabilization at the air-water interface through competitive adsorption.","authors":"Julie Garcia Gonzalez-Calero, Harri Rahn, Kan Wu, Josepha Roerig, Fabian Seebacher, Nikolai Hentze, Markus Hollmann, Dirk Grimm, Chen Zhou","doi":"10.1016/j.xphs.2026.104304","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104304","url":null,"abstract":"This study investigated the stabilization of adeno-associated viruses (AAVs) at the air-water interface (AWI), focusing on the interplay between surfactant and capsid adsorption during agitation stress. AAV-9 and its engineered variant, AAV-PHP.eB-known for enhanced central nervous system tropism-were subjected to orbital shaking to simulate interfacial stress encountered during manufacturing and transportation. The impact of surfactant type and concentration was systematically evaluated using polysorbates 20 and 80, Poloxamer 188 (P 188), and Kolliphor® HS15. Size-exclusion chromatography-multi-angle light scattering (SEC-MALS) and total holographic characterization (THC) provided insights into capsid titer recovery and subvisible particle (SVP) formation. Hydrophobic interaction chromatography (HIC) and pendant drop shape analysis revealed striking differences in surface hydrophobicity and activity between the AAV variants. Our results suggested that AAV-PHP.eB, with higher surface hydrophobicity and activity, suffered greater adsorption and SVP formation than AAV-9, requiring higher P 188 concentrations for effective stabilization. At 0.1 % (w/v) P 188, a shift in SVP populations was detected by THC and Dynamic Light Scattering with the emergence of rod-like and irregularly shaped particles, likely representing P 188 aggregates. The findings suggest that greater P 188 concentration not only offers protection by saturating the AWI and direct binding to the capsid, but may also form aggregate structures in presence of AAVs that further impede capsid adsorption and aggregation.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104304"},"PeriodicalIF":3.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0