Journal of pharmaceutical sciences最新文献_第10页

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-03-01 Epub Date: 2026-02-27 DOI: 10.1016/S0022-3549(26)00053-5

引用次数: 0

Extracellular vesicles from microalgae Pavlova in non-heated condition potently enhance innate immune response as a novel cell-derived immunostimulatory adjuvant 巴甫洛娃微藻细胞外囊泡作为一种新型细胞源性免疫刺激佐剂，在非加热条件下可增强先天免疫应答。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-03-01 Epub Date: 2026-01-10 DOI: 10.1016/j.xphs.2026.104158

Masaki Morishita , Kotaro Yamada , Toshio Taira , Ken Nakahara , Tomonori Waku , Kotone Minato , Ken-ichi Ogawara

{"title":"Extracellular vesicles from microalgae Pavlova in non-heated condition potently enhance innate immune response as a novel cell-derived immunostimulatory adjuvant","authors":"Masaki Morishita , Kotaro Yamada , Toshio Taira , Ken Nakahara , Tomonori Waku , Kotone Minato , Ken-ichi Ogawara","doi":"10.1016/j.xphs.2026.104158","DOIUrl":"10.1016/j.xphs.2026.104158","url":null,"abstract":"<div><div>In vaccine therapy, there is a growing interest in novel immunostimulatory adjuvants derived from food products or dietary supplements with safe profiles. <em>Pavlova</em> is a microalga commonly used as a dietary supplement. Owing to its immune-activating potency and safety profiles, <em>Pavlova</em> offers novel possibilities as an immunostimulatory adjuvant. However, precise control of their proliferation profile and subsequent immune activation when administered to the host is difficult, limiting their practicality as adjuvants. Extracellular vesicles (EVs) are cell-derived nanoparticles containing nucleic acids and proteins. EVs exhibit biological activity without proliferating, indicating their potential in medical applications as novel cell-free materials. However, information on EVs secreted by microalgae, including <em>Pavlova</em>, is limited. In this study, we characterized the EVs from <em>Pavlova</em> as an immunostimulatory adjuvant. Heated <em>Pavlova</em>-derived EVs (hP-EVs) and non-heated <em>Pavlova</em>-derived EVs (n-hP-EVs) were purified from their culture supernatants, with heated <em>Pavlova</em> secreting larger amounts of EVs. These EVs exhibited a particle size of approximately 130–170 nm and a negatively-charged zeta potential. RAW264.7 macrophage cells more actively took up n-hP-EVs than hP-EVs via endocytosis. As an adjuvant activity, n-hP-EVs potently increased the production of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which are indicators of enhanced innate immune response. Moreover, the effect of the storage temperature on the particle size of n-hP-EVs was small, maintaining their ability to activate innate immune responses. Thus, n-hP-EVs demonstrate attractive characteristics for use as novel cell-derived immunostimulatory adjuvants.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104158"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959407","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

Investigating the SNAC-to-drug ratio for the oral absorption of cyanocobalamin in rats 研究大鼠口服氰钴胺素吸收的snc -药比。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-03-01 Epub Date: 2026-01-13 DOI: 10.1016/j.xphs.2026.104163

Po-Chang Chiang , Jia Liu , Karthik Nagapudi , Jodie Pang , Emile Plise , Michael Dolton , Matthew R. Durk

{"title":"Investigating the SNAC-to-drug ratio for the oral absorption of cyanocobalamin in rats","authors":"Po-Chang Chiang , Jia Liu , Karthik Nagapudi , Jodie Pang , Emile Plise , Michael Dolton , Matthew R. Durk","doi":"10.1016/j.xphs.2026.104163","DOIUrl":"10.1016/j.xphs.2026.104163","url":null,"abstract":"<div><div>The oral route of administration continues to be the preferred and most convenient method for drug delivery among both patients and healthcare professionals. This preference is based not only on its user-friendliness but also on the practicality it provides regarding formulation flexibility and dosage adjustability. Nevertheless, the effectiveness of oral drug delivery is significantly influenced by the ADME (Absorption, Distribution, Metabolism, and Excretion) characteristics of the drug. Among these characteristics, permeability is a key factor affecting oral bioavailability, making the exploration of permeability enhancers a vital research focus to boost oral absorption. Recent investigations have highlighted sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) as a promising permeability enhancer, demonstrating its potential to increase the absorption rates of various substances. Despite its proven effectiveness, the precise mechanisms by which SNAC promotes this enhancement are not yet fully understood. Furthermore, the specific dosage of SNAC required to improve drug absorption remains unclear. This study aims to examine the dose-dependent effects of SNAC on the model compound cyanocobalamin (Vitamin B12) in rats. The in vivo findings were integrated with modeling and simulation to determine the critical concentration of SNAC and the minimum molar ratio, and the overall enhancement effect at various SNAC concentrations for cyanocobalamin needed to achieve permeation enhancement. This knowledge could assist formulators in more effectively incorporating SNAC into formulations for enhanced therapeutic outcomes.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104163"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989798","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

Ionic strength mitigates solvent/detergent–induced tertiary expansion of hemopexin 离子强度减轻溶剂/清洁剂引起的血凝素三级膨胀。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-03-01 Epub Date: 2026-01-14 DOI: 10.1016/j.xphs.2026.104166

Min-Jung Kim , Jaeeun Jung , Jieun Kang , Nohra Park , Sung Jun Lee , Geunhye Yeo , Sangho Lee

{"title":"Ionic strength mitigates solvent/detergent–induced tertiary expansion of hemopexin","authors":"Min-Jung Kim , Jaeeun Jung , Jieun Kang , Nohra Park , Sung Jun Lee , Geunhye Yeo , Sangho Lee","doi":"10.1016/j.xphs.2026.104166","DOIUrl":"10.1016/j.xphs.2026.104166","url":null,"abstract":"<div><div>Hemopexin (Hx) is a plasma glycoprotein that scavenges free heme with sub-nanomolar affinity and under development as a therapeutic. Solvent/detergent treatment (S/D) is routinely applied to plasma-derived manufacturing for viral safety and generally considered non-disruptive. However, the histidine- and aromatic residue-rich heme pocket at the inter-domain interface may render Hx susceptible to S/D. We investigated whether S/D perturbs the tertiary structure of Hx and elevated ionic strength mitigates such effects. Changes in the apparent size and activity of Hx exposed to S/D were assessed by size-exclusion HPLC (SE-HPLC) and functional assays. S/D consistently reduced activity and shifted SE-HPLC profiles toward a larger hydrodynamic size. Small-angle X-ray scattering (SAXS) revealed expansion of the molecular envelope of Hx by S/D, suggesting that the heme pocket may initiate hinge relaxation between two β-propeller domains of Hx. To mitigate such expansion by S/D, we screened a formulation range of NaCl concentration. Increasing ionic strength compacted SAXS profiles toward the native state and restored activity, consistent with pocket stabilization by charge. These findings identify Hx as an exception to typical S/D tolerance and demonstrate that modulation of ionic strength represents an effective strategy to preserve structural integrity and function while fulfilling viral safety requirements.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104166"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989735","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

Design and synthesis of carbamate-linked ester prodrugs selectively activated by carboxylesterase 1 with enhanced stability against intestinal hydrolysis 羧酸酯酶1选择性激活氨基甲酸酯前药的设计与合成，增强了抗肠道水解的稳定性。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-02-01 Epub Date: 2025-12-25 DOI: 10.1016/j.xphs.2025.104146

Masato Takahashi, Shintaro Sakamoto, Nao Sakamoto, Sora Nishimura, Seonho Hwang, Jihyun Kim, Masakiyo Hosokawa

{"title":"Design and synthesis of carbamate-linked ester prodrugs selectively activated by carboxylesterase 1 with enhanced stability against intestinal hydrolysis","authors":"Masato Takahashi, Shintaro Sakamoto, Nao Sakamoto, Sora Nishimura, Seonho Hwang, Jihyun Kim, Masakiyo Hosokawa","doi":"10.1016/j.xphs.2025.104146","DOIUrl":"10.1016/j.xphs.2025.104146","url":null,"abstract":"<div><div>Ester-based prodrugs are often prematurely hydrolyzed by intestinal carboxylesterases, leading to reduced bioavailability and potential gastrointestinal (GI) toxicity. To overcome this limitation, a series of diester, carbonate-linked ester, and carbamate-linked ester prodrugs were synthesized and evaluated using human liver microsomes (HLM), human intestinal microsomes (HIM), and recombinant carboxylesterases (CES1A1 and CES2A1). Under strongly acidic conditions (pH 1.2), all prodrugs remained highly stable (>98% remaining after 6 h). In human plasma, however, diester prodrugs showed relatively rapid degradation (approximately 50% remaining after 6 h), whereas carbonate- and carbamate-linked esters displayed enhanced stability. Diester and carbonate-linked ester prodrugs were hydrolyzed by both HLM and HIM, indicating non-selective activation. By contrast, several carbamate-linked ester prodrugs showed high HLM/HIM selectivity, with CES1A1/CES2A1 hydrolysis rate ratios exceeding 50. Docking simulations showed favorable active-site binding of carbamate-linked ester prodrugs to CES1A1 but not to CES2A1, supporting the selectivity of CES1A1. These findings suggest that carbamate-based prodrug strategies can be employed to improve intestinal stability and enable controlled systemic activation, potentially reducing off-target effects and enhancing oral drug delivery. This strategy may also be applicable to liver- or lung-targeted prodrug design.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104146"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846798","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 multicompartment stomach physiologically-based pharmacokinetic model capturing gastric reacidification can improve food effect predictions of weak bases 捕获胃再酸化的多室胃生理药代动力学模型可以改善弱碱的食物效应预测。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-02-01 Epub Date: 2026-01-03 DOI: 10.1016/j.xphs.2026.104155

Lisa Cheng , Po-Chang Chiang , Matthew R Wright , Harvey Wong

{"title":"A multicompartment stomach physiologically-based pharmacokinetic model capturing gastric reacidification can improve food effect predictions of weak bases","authors":"Lisa Cheng , Po-Chang Chiang , Matthew R Wright , Harvey Wong","doi":"10.1016/j.xphs.2026.104155","DOIUrl":"10.1016/j.xphs.2026.104155","url":null,"abstract":"<div><div>Various changes within the gastrointestinal tract following meal intake may significantly impact oral drug absorption. Physiologically-based pharmacokinetic (PBPK) models are often used to perform early predictions of food effects on oral absorption. However, the stomach compartment within these physiological models does not wholly reflect physiology of the fed state. The current approach where the stomach compartment is fixed at pH 5 overlooks the changing gastric pH profile over time after food consumption. We suggest the integration of a multicompartment stomach that represents the various pH phases of the fed stomach to better capture ionizable drug dissolution. Ibuprofen sodium (weak acid) and posaconazole (weak base) were investigated to determine whether a PBPK model that could better capture the varying gastric pH would yield an improvement in food effect predictions. The one-compartment and multicompartment stomach models’ simulations for ibuprofen sodium exposure with and without food consumption were comparable. For posaconazole, the one-compartment stomach model predicted a smaller area under the curve and lower maximum plasma concentration than the multicompartment stomach model’s output in the fed state. Although both models accurately predicted a positive food effect, the magnitude of the simulated fed to fasted fold-changes in posaconazole exposure by the one-compartment stomach model was much less than observed fold-changes. These results suggest that a multicompartment stomach model featuring gastric re-acidification associated with food intake should be incorporated for more accurate food effect predictions for weakly basic compounds.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104155"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906249","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

Paper-based reaction devices as accelerated platforms in forced degradation studies 纸基反应装置在强制降解研究中的加速平台。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-02-01 Epub Date: 2025-12-04 DOI: 10.1016/j.xphs.2025.104111

Airton G. Salles Jr. , Willian R. de Araujo , Manoel T. Rodrigues Jr. , Bruno B. Guidotti

{"title":"Paper-based reaction devices as accelerated platforms in forced degradation studies","authors":"Airton G. Salles Jr. , Willian R. de Araujo , Manoel T. Rodrigues Jr. , Bruno B. Guidotti","doi":"10.1016/j.xphs.2025.104111","DOIUrl":"10.1016/j.xphs.2025.104111","url":null,"abstract":"<div><div>The stability of pharmaceutical compounds is a central concern in drug development, as degradation can compromise both efficacy and safety. Conventional forced degradation studies, while effective, are often time-consuming and resource-intensive, highlighting the need for accessible and high-throughput alternatives. In this study, we introduce paper-based reaction devices (PRDs) as an innovative platform for accelerating drug degradation experiments. Strips of cellulose paper were employed as reactive microenvironments to investigate the degradation of two model drugs, cyclobenzaprine (CBP) and deflazacort (DFL), under oxidative, acidic, basic, and metal-ion stress conditions. Chromatographic analysis using HPLC-PDA and high-resolution mass spectrometry (HRMS) revealed that the paper interface preserved mechanistic relevance, yielding degradation profiles consistent with solution-based studies while markedly enhancing degradation rates. Mechanistic trends were consistent with the hypothesis that hydroxyl-rich cellulose surfaces promote kinetic amplification through hydrogen-bond-mediated microconfinement. Mass-balance assessments demonstrated reproducibility and validated the reliability of the approach across stress conditions. The PRD approach is proposed as an investigational and preformulation-level tool for early-phase stability assessment, complementing rather than replacing conventional stress testing methods. Its simple, robust, and high-throughput format offers a valuable alternative for rapid stability evaluation during the early stages of drug development and formulation design.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104111"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696044","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

Lipid-free, thermostable mRNA vaccines prepared using atomic layer deposition 利用原子层沉积制备无脂、耐热的mRNA疫苗。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-02-01 Epub Date: 2025-11-13 DOI: 10.1016/j.xphs.2025.104066

Holly J. Coleman , Amber Rauch , Erika Langsfeld , Kimberly Anderson , Urvi Parlikar , Hans H. Funke , Robert L. Garcea , Theodore W. Randolph

{"title":"Lipid-free, thermostable mRNA vaccines prepared using atomic layer deposition","authors":"Holly J. Coleman , Amber Rauch , Erika Langsfeld , Kimberly Anderson , Urvi Parlikar , Hans H. Funke , Robert L. Garcea , Theodore W. Randolph","doi":"10.1016/j.xphs.2025.104066","DOIUrl":"10.1016/j.xphs.2025.104066","url":null,"abstract":"<div><div>Lipid nanoparticle (LNP) formulations of mRNA vaccines have played a pivotal role in combatting SARS-CoV-2 infections and are expected to be a useful vaccine modality against other pathogens. However, the instability of mRNA-LNP vaccines requires their storage at temperatures below 0 °C and presents manufacturing challenges. We describe thermally stable, lipid-free mRNA vaccines prepared by spray-drying to embed mRNA within glassy polysaccharide microparticles, followed by atomic layer deposition (ALD) to encapsulate the microparticles within protective alumina shells that provide temporally controlled antigen release and facilitate cellular uptake. Using mRNAs encoding for ovalbumin, the modified HIV envelope trimer protein N332-GT2, and green fluorescent protein (GFP), we show that alumina-coated microparticles containing lipid-free mRNA are internalized by cultured macrophages <em>in vitro,</em> elicit robust immune responses compared to LNP-based mRNA vaccines <em>in vivo,</em> and are stable when stored for 6 months at temperatures up to 40 °C. Thus, alumina-coated mRNA vaccines may overcome current limitations of mRNA-LNP vaccines without using LNPs or other lipid-based carriers.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104066"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530726","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

Outstanding early career scientists for 2025 2025杰出早期职业科学家。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-02-01 Epub Date: 2025-11-19 DOI: 10.1016/j.xphs.2025.104073

Kenneth L. Audus

引用次数: 0

Preparation and characterization of oral insulin-trimethyl chitosan complex-loaded solid self-nanoemulsifying drug delivery systems (SNEDDS) 口服胰岛素-三甲基壳聚糖复合物负载固体自纳米乳化给药系统的制备与表征。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-02-01 Epub Date: 2025-12-30 DOI: 10.1016/j.xphs.2025.104149

Richieline S. Cual, Tajmarah Ayyah M. Sandato, Mae Quenie T. Pontanar

{"title":"Preparation and characterization of oral insulin-trimethyl chitosan complex-loaded solid self-nanoemulsifying drug delivery systems (SNEDDS)","authors":"Richieline S. Cual, Tajmarah Ayyah M. Sandato, Mae Quenie T. Pontanar","doi":"10.1016/j.xphs.2025.104149","DOIUrl":"10.1016/j.xphs.2025.104149","url":null,"abstract":"<div><div>Insulin, a pancreatic hormone regulating blood glucose, is available in forms of syringe, pen, or implants; however, these methods presented challenges related to skin adverse reactions and patient compliance. Oral insulin delivery has long been explored due to higher compliance and reduced costs. Similar to natural insulin secretion, but prone to GIT breakdown and low bioavailability. SNEDDS has been investigated to address these in protein formulations. This study formulated Insulin into SNEDDS with trimethyl chitosan and spray-dried for stability, then analyzed for properties and drug release. The study successfully prepared Insulin-TMC SNEDDS with a 36.17±4.02 s emulsification time, forming a Grade B nanoemulsion. Droplet sizes remained nanoscale (134.20–287.20 nm for liquid, 188.77–214.93 nm for solid), preserving characteristics post–spray drying. Stability was confirmed in TMC-free formulations, while TMC variants showed sedimentation over time. TMC-containing Solid-SNEDDS showed moisture content below 5 %, indicating good stability. Insulin release varied with pH—highest at pH 2.5 with 3 mg/mL TMC (105.48 % cumulative percent drug release), while lower releases were seen at pH 6.6 (61.73±1.38 %) and 7.0 (61.73±1.38 %) without TMC. The study supports TMC-based SNEDDS and spray drying as a potential method for oral insulin delivery.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104149"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889374","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