Journal of pharmaceutical sciences最新文献

Pediatric extended-release oral formulations: A U.S. market landscape analysis. 儿科缓释口服配方：美国市场景观分析。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-05-07 DOI: 10.1016/j.xphs.2026.104319

Hwee Jing Ong, Y-H Kiang, Bhanu Bejgum, Behnoush Khorsand, Fernando Alvarez-Nunez

{"title":"Pediatric extended-release oral formulations: A U.S. market landscape analysis.","authors":"Hwee Jing Ong, Y-H Kiang, Bhanu Bejgum, Behnoush Khorsand, Fernando Alvarez-Nunez","doi":"10.1016/j.xphs.2026.104319","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104319","url":null,"abstract":"Extended-release (ER) oral formulations provide therapeutic and practical benefits for pediatric patients by minimizing fluctuations in systemic exposure, reducing dosing frequency, and improving adherence. However, few reviews of ER formulations have focused specifically on the pediatric population. Accordingly, this review has two objectives. The first objective is to characterize the current U.S. market landscape of pediatric ER oral drug products using the U.S. Food and Drug Administration (FDA) Pediatric Labeling Changes database (1998 - 2023). The second objective is to evaluate the extent to which existing products address pediatric needs and to identify opportunities for future development based on the findings of this analysis. In the current U.S. market, 42 out of 266 pediatric-labeled oral prescription drugs are ER products. These products are concentrated in attention-deficit/hyperactivity disorder and seizure indications, and most are labeled for children 6 years of age and older. Conventional tablets and multiparticulate capsules are the predominant dosage forms, whereas suspensions, orally disintegrating tablets, and chewable tablets are less commonly represented. Four principal technology platforms are used: matrix systems, ion-exchange resins, functional coatings, and osmotic pumps, often in combination to balance child-appropriate administration with robust release performance. The analysis highlights several opportunities for future development. Expanding ER development into additional chronic pediatric conditions, addressing the lack of options for children younger than 6 years of age, and strengthening pre-competitive knowledge sharing on formulation platforms and technologies represent the key priorities for broadening the availability of safe, effective, and child-friendly ER medicines.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104319"},"PeriodicalIF":3.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864225","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

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

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

Non-viral in vivo cell and gene therapies: A change journey for CMC science and scientists. 非病毒体内细胞和基因治疗：CMC科学和科学家的变革之旅。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-05-01 DOI: 10.1016/j.xphs.2026.104312

Annette Bak, Marianne Ashford

{"title":"Non-viral in vivo cell and gene therapies: A change journey for CMC science and scientists.","authors":"Annette Bak, Marianne Ashford","doi":"10.1016/j.xphs.2026.104312","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104312","url":null,"abstract":"The CMC (Chemistry Manufacturing and Controls) landscape is rapidly evolving as pharmaceutical science shifts from traditional small molecules and peptides towards non-viral in vivo cell and gene therapies. The article highlights the skills required including hybrid scientific roles spanning chemistry, biology, drug delivery, formulation and analytical development. They are essential to deliver clinical non-viral in vivo cell and gene therapy products. In addition, organizational structures that are best suited for these new therapies are discussed. To frame the discussion on skills, we briefly start out by summarizing the increased modality complexity in terms of multicomponent LNPs (lipid nanoparticles), including novel excipients, new product manufacturing methods, complex analytical requirements, and a regulatory framework that is still developing. Finally, it is highlighted how non-viral in vivo cell and gene therapies will have clinical and patient access advantages. We hope to provide inspiration for scientists on a similar journey and demonstrate that expanding your skills, knowledge and science is a worthwhile undertaking to aid in developing the differentiated medicines of the future.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104312"},"PeriodicalIF":3.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816529","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

Effect of transcript length, temperature, and lyophilization on mRNA-lipid nanoparticle stability. 转录物长度、温度和冻干对mrna -脂质纳米颗粒稳定性的影响。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-05-01 DOI: 10.1016/j.xphs.2026.104308

Manasa Chillara, Weibo Zhao, Jonathan S Dordick, Todd Przybycien

{"title":"Effect of transcript length, temperature, and lyophilization on mRNA-lipid nanoparticle stability.","authors":"Manasa Chillara, Weibo Zhao, Jonathan S Dordick, Todd Przybycien","doi":"10.1016/j.xphs.2026.104308","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104308","url":null,"abstract":"Lyophilization enhances the long-term stability of mRNA-lipid nanoparticles (LNPs), yet the full extent of the physicochemical and functional implications of freeze-drying remains underexplored. In the current work, the influence of key variables, such as mRNA length, formulation conditions, and lyophilization status, on the stability of mRNA-LNPs was investigated. mRNA constructs were synthesized encoding monomeric (egfp)1, dimeric (egfp)2, and tetrameric (egfp)4 sequences to vary mRNA length systematically. A suitable LNP composition and lyophilization conditions were identified to generate lyophilized mRNA-LNPs for a long-term stability study. The physicochemical properties of mRNA-LNPs changed initially after lyophilization but were stable during storage for both lyophilized and aqueous samples. However, these properties did not reliably predict functional stability. Aqueous (egfp)1-LNPs stored at room temperature showed a rapid 50-fold decrease in enhanced green fluorescent protein (EGFP) expression within 28 days. In contrast, lyophilized mRNA-LNPs underwent only a 6-fold loss in EGFP expression at 28 days, followed by a gradual decline to a 9-fold loss at 84 days. Lyophilization appears to result in two or more LNP subpopulations, leading to functional heterogeneity. Furthermore, inactivation rate constants were calculated using a first-order rate model as a function of temperature and mRNA length, which can serve as a basis for future mRNA-LNP stability modeling.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104308"},"PeriodicalIF":3.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816499","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