Journal of pharmaceutical sciences最新文献

{"title":"Immunogenicity of biologics delivered in the subcutaneous space: Delineating the contributing factors.","authors":"Vibha Jawa, Sophie Tourdot, Manjunath Shivaraju, Marisa Joubert, Sathy Balu-Iyer, Kari Cox, Ming Cheng, Ying Chen, Masano Huang, Karoline Bechtold Peters, Jochem Gokemeijer, Sy Gebrekidan, Alison Johnson, Marie Printz, Manuel Sanchez-Felix, Erik Meyer, Sachin Mittal, Amy Rosenberg, Nicole Buist","doi":"10.1016/j.xphs.2026.104527","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104527","url":null,"abstract":"<p><p>The subcutaneous (SC) route of administration for therapeutic proteins (TPs) offers advantages such as patient convenience, reduced delivery complexity, and self-administration leading to enhanced adherence. Although SC delivery may be perceived to have higher immunogenicity risk than intravenous (IV) administration due to longer antigen exposure and proximity to resident professional immune cells, recent data suggest that immunogenicity rates of TPs are comparable between SC and IV administration routes. Factors thought to contribute to immunogenicity risk encompass dosing regimen (route of administration), and patient and product-related elements. Product related factors include liabilities related to protein sequence, critical quality attributes that may occur during process development and manufacturing such as post-translational modifications, propensity to aggregate, presence of impurities, and the drug's mechanism of action. Advances in formulation, delivery systems, molecular design and associated biophysical characterization can help mitigate some of these risks. The Immunogenicity Sub team of the Subcutaneous Drug Development & Delivery Consortium, held a workshop at the 2023 PEGS Boston meeting, focused on delineating the immunogenicity risk factors carried by SC administration. In this paper, the team presents the outcome of the workshop and discusses the most recent clinical examples of SC administration which highlight that the SC route is not inherently more immunogenic than IV administration and requires context-specific evaluation. Additionally, the paper provides an overview of the current landscape in non-clinical immunogenicity risk assessment focused on novel in vivo and in vitro models, together with identified gaps and opportunities for further improvement of immunogenicity prediction as it relates to SC route.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104527"},"PeriodicalIF":3.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127741","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}

{"title":"CAGE ionic liquid-mediated co-solubilization of lapatinib and resveratrol enhances cytotoxicity in lung cancer cells with uniform aerosolization for pulmonary delivery.","authors":"Nidhi Singh, Kolimi Prasanth Reddy, Rudra Chakravarti, Navratan Soni, David Paul, Dipanjan Ghosh, Pallab Datta","doi":"10.1016/j.xphs.2026.104534","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104534","url":null,"abstract":"<p><p>Choline and geranic acid-based ionic liquids (CAGE-IL) have emerged as powerful delivery vehicles for many challenging drug molecules via different routes of administration. However, their potential for aerosol delivery has not been reported. In this study, CAGE-IL is investigated for its ability to solubilise a combination of lapatinib ditosylate (LPT) and resveratrol (RSV) as a potential vehicle for localised delivery in lung cancer therapy. The results showed that CAGE-IL had much higher solubility for LPT (114.6 ± 3.5 mg/mL vs. 0.02 mg/mL) and RSV (58.1 ± 6.8 mg/mL vs. 0.03 mg/mL) than their respective aqueous solubilities, as determined using a validated HPLC method developed for the simultaneous estimation of the molecules. An octanol/water partition coefficient of 2.34 for LPT from LPT-CAGE-IL and 2.18 for RSV from RSV-CAGE-IL was obtained. Upon evaluation in A549, a lung adenocarcinoma cell line, the IC₅₀ value of LPT+RSV-co-loaded CAGE-IL was significantly lower (1.2 times, p˂0.006) than LPT solution (5.3 times, p˂0.0001) or RSV solution (2.7 times, p˂0.001). Importantly, we performed the first nebulization efficiency characterisation for CAGE-IL, obtaining 48 ± 1% for LPT and 49 ± 1% for RSV, with drug output rates of 15 mg/min for LPT and 7 mg/min for RSV and D₅₀ of 2.74 µm. The MMAD, FPF, and GSD were 2.00 ± 0.2 µm, 74 ± 5 %, and 2.48 ± 0.2 for RSV, and 2.10 ± 0.3 µm, 70 ± 7 %, and 2.87 ± 0.2 for LPT showing the suitability of the prepared formulation for pulmonary use. Overall, achieving high solubility of both drugs in a single medium, along with near-identical recovery, signified uniform co-aerosolisation without phase separation during nebulization, indicating CAGE-IL as a possible vehicle for inhalation delivery, and enhance the therapeutic efficacy for localised lung cancer treatment.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104534"},"PeriodicalIF":3.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127702","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}

{"title":"Composition-dependent changes in the crystallization mechanism in drug-drug coamorphous systems of related neuropeptide Y Y5 receptor antagonists.","authors":"Hiroshi Ueda, Hironori Tanaka, Yuna Shimazaki, Shohei Aikawa","doi":"10.1016/j.xphs.2026.104532","DOIUrl":"10.1016/j.xphs.2026.104532","url":null,"abstract":"<p><p>This study investigated the stabilization mechanisms of coamorphous systems using the related neuropeptide Y Y5 receptor antagonists NPY(A) and NPY(B). Physical mixtures (PMs) formed a eutectic mixture at an equimolar ratio. Thermal analysis during melting-cooling showed a single glass transition temperature (Tg) for each drug and the PMs, indicating amorphization of the individual drugs and coamorphization of NPY(A)-NPY(B). The Tg of NPY(A) was higher than that of NPY(B). Annealing at 15-17°C below Tg increased the Tg of all samples through structural relaxation. However, the τ^β values obtained from both the Kohlrausch-Williams-Watts equation and ΔTg did not increase after coamorphization. Annealing promoted nucleation and accelerated crystallization of NPY(A), but not NPY(B). These phenomena were also observed in the coamorphous systems, suggesting composition-dependent crystallization mechanisms. Infrared spectroscopy revealed weak intermolecular interactions in the coamorphous systems. Isothermal crystallization tests showed that NPY(A)-rich and NPY(B)-rich coamorphous systems were stabilized by Tg elevation and nucleation inhibition, respectively. Spray-dried coamorphous systems exhibited improved stability and enhanced dissolution of both drugs in pH 6.8 phosphate buffer.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104532"},"PeriodicalIF":3.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127719","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}

{"title":"Comment on “Improved sub-visible particle classification in flow imaging microscopy via generative AI-based image synthesis”","authors":"V. Senthilkumar,&nbsp;Pratik Mungekar,&nbsp;R. Vasanthan","doi":"10.1016/j.xphs.2026.104440","DOIUrl":"10.1016/j.xphs.2026.104440","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 10","pages":"Article 104440"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604286","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}

{"title":"Reply to the comment on “improved sub-visible particle classification in flow imaging microscopy via generative AI-based image synthesis”","authors":"Utku Ozbulak,&nbsp;Michaela Cohrs,&nbsp;Hristo L. Svilenov,&nbsp;Joris Vankerschaver,&nbsp;Wesley De Neve","doi":"10.1016/j.xphs.2026.104441","DOIUrl":"10.1016/j.xphs.2026.104441","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 10","pages":"Article 104441"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620635","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}

{"title":"Editorial Advisory Board","authors":"","doi":"10.1016/S0022-3549(26)00348-5","DOIUrl":"10.1016/S0022-3549(26)00348-5","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 10","pages":"Article 104498"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Advisory Board","authors":"","doi":"10.1016/S0022-3549(26)00321-7","DOIUrl":"10.1016/S0022-3549(26)00321-7","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 9","pages":"Article 104471"},"PeriodicalIF":3.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149051003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on “A quantitative metric of immune responses with applications in vaccines, cancer immunity, autoimmunity, and anti-drug antibody monitoring”","authors":"Shobana Chandrasekar,&nbsp;Rohith Krishn M. K,&nbsp;Umesh Kumar","doi":"10.1016/j.xphs.2026.104330","DOIUrl":"10.1016/j.xphs.2026.104330","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 9","pages":"Article 104330"},"PeriodicalIF":3.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147960019","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}

{"title":"Comment on “Nano-enabled targeted transdermal therapy for pain management in cervical cancer”","authors":"Shubham Kamble,&nbsp;Gulshan Gurunani,&nbsp;Mitali Bodhankar","doi":"10.1016/j.xphs.2026.104421","DOIUrl":"10.1016/j.xphs.2026.104421","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 9","pages":"Article 104421"},"PeriodicalIF":3.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471328","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}

{"title":"Comment from Bhardwaj et al on “Comprehensive stress study on recombinant adeno-associated virus vectors: Evaluating the capabilities of established analytical techniques”","authors":"Abhay Bhardwaj,&nbsp;Daksh Bhatia,&nbsp;Anuj Pathak,&nbsp;Latika Sharma","doi":"10.1016/j.xphs.2026.104353","DOIUrl":"10.1016/j.xphs.2026.104353","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 9","pages":"Article 104353"},"PeriodicalIF":3.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199282","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}