Journal of pharmaceutical sciences最新文献

{"title":"Developing ultra-high concentration formulations of human immune globulins for subcutaneous injectables","authors":"Jayprakash Yadav ,&nbsp;Shihab Uddin ,&nbsp;Francesco Civati ,&nbsp;Wenchuan Ma ,&nbsp;Andreas Liebminger ,&nbsp;Wolfgang Teschner ,&nbsp;Guillaume André ,&nbsp;Bernhardt L. Trout ,&nbsp;Richard D. Braatz ,&nbsp;Allan S. Myerson","doi":"10.1016/j.xphs.2025.01.028","DOIUrl":"10.1016/j.xphs.2025.01.028","url":null,"abstract":"<div><div>This work describes the first development of high-concentration suspension formulations of human immune globulin. Colloidal-level dispersions of immune globulin were achieved by suspending a spray dried solid powder of protein in a protein solution made saturated by the addition of pharmaceutical excipients. The spray drying process was used to generate ∼90 % of particles below 20μ. The monomer and aggregates content of immunoglobulin were found to be 93 % and 0.3 %, respectively. The injection forces for the colloidal suspensions were characterized using a dynamic compression test. The concentrations of 300, 380, and 400 mg/mL formulations were injected at 3.8 N, 10 N, and 16.5 N of maximum injection forces, respectively, when a 24-gauge needle was used. The viscosity of a 300 mg/mL suspension was 128 cP. The viscosity of a 380 mg/mL suspension was 284 cP, and the viscosity was higher for the 400 mg/mL formulation; however, injectability was not an issue, which remains rare for non-Newtonian, shear-thickening systems. It is acknowledged that the 400 mg/mL suspension formulation remained relatively challenging as compared to other suspensions for injection because of its very high viscosity, and significant force was required to inject it. We show that where ultra-high-concentration immune globulin is being developed within reasonable constraints of pharmaceutical regulation, with an injectability parameter, formulations might make their way to the clinic when viscosity could say otherwise. However, further work should be conducted to assess chemical stability (using methods such as mass spectrometry) along with forced degradation studies prior any clinical use.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 3","pages":"Pages 1605-1614"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255566","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":"A spleen-targeted vaccine for SARS-CoV-2 — Inducting neutralizing antibodies in mice","authors":"Taro Shimizu ,&nbsp;Shunji Abe ,&nbsp;Yoshino Kawaguchi ,&nbsp;Haruka Takata ,&nbsp;Hidenori Ando ,&nbsp;Tatsuhiro Ishida","doi":"10.1016/j.xphs.2025.01.024","DOIUrl":"10.1016/j.xphs.2025.01.024","url":null,"abstract":"<div><div>The development of vaccines against infectious diseases is of the utmost importance to prevent global pandemics such as COVID-19. The application of antigens and adjuvants to efficiently target antigen presenting cells (APCs) is paramount for the development of efficient vaccines. In our previous study, we showed that splenic marginal zone-B (MZ-B) cells are promising APCs in addition to dendritic cells (DCs). In this study we achieved the targeted delivery of sufficient antigen to MZ-B cells by utilizing an intravenous (IV) immunization system we originally developed. This system involves the sequential injection of empty PEGylated liposomes (PEG-Lip) and antigen-containing PEG-Lip within a prescribed interval. Herein, we describe the application of this IV immunization system as a COVID-19 vaccine to induce specific antibodies against SARS-CoV-2. To establish efficacy, SARS-CoV-2 spike proteins were used as an antigen, and α-galactosylceramide (GC) was used as an adjuvant in this study. Three days after priming with empty PEG-Lip, we injected PEG-Lip containing spike protein and α-GC. Our IV immunization system successfully induced higher levels of anti-spike antibodies when spike protein derived from HEK-293, but not E. coli., was injected into mice. The levels were less produced using conventional immunization via subcutaneous (s.c.) injections of complete Freund's adjuvant without priming. Interestingly, a lower dose (0.2 µg) of spike protein antigen encapsulated into PEG-Lip induced a higher level of anti-spike antibodies than that produced using a significantly higher dose (5 µg). The induced anti-spike antibodies inhibited the interaction between the receptor binding domain of the spike protein and the angiotensin-converting enzyme 2. This indicates that the induced antibodies tend to neutralize SARS-CoV-2. Collectively, the specific delivery of spike proteins to spleen, probably MZ-B cells, via nano-carriers could be a promising approach for the development of global pandemic vaccines that require only minimum dosages of antigen.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 3","pages":"Pages 1615-1624"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074862","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":"Novel hybrid system based on carboxymethyl chitosan hydrogel encapsulating drug loaded nanoparticles for prolonged release of Vancomycin in the treatment of bacterial infection","authors":"Lixia Pan ,&nbsp;Dandan Wang ,&nbsp;Haozhi Sun ,&nbsp;Jie Song ,&nbsp;Xin Shen ,&nbsp;Feng Su ,&nbsp;Suming Li","doi":"10.1016/j.xphs.2025.01.012","DOIUrl":"10.1016/j.xphs.2025.01.012","url":null,"abstract":"<div><div>Current bacterial infections clinical treatments, such as intravenous antibiotic administration and local injection, suffer from short action duration, repeated administrations, and severe cell toxicity. To address these limitations, it is imperative to develop sustained drug release system with prolonged antimicrobial effects. In this work, a hybrid system was prepared using EDC/NHS catalyzed crosslinking-based carboxymethyl chitosan (CMCS) hydrogel as a carrier to encapsulate biodegradable nanoparticles (NPs) loaded with vancomycin, an efficient antibacterial drug. First, ring opening polymerization of L-lactide or L-lactide/glycolide mixture was performed in the presence of poly(ethylene glycol) (PEG) to yield PEG-PLA or PEG-PLGA block copolymers. Vancomycin was loaded in PEG-PLA or PEG-PLGA NPs using double emulsion method. Drug-loaded NPs were then encapsulated in the CMCS hydrogel. Drug release from NPs, CMCS hydrogel and hybrid NPs-hydrogel systems was performed, and release kinetics were analyzed using Korsmeyer-Peppas model. The established hybrid system exhibited prolonged drug release without burst release. Finally, the biocompatibility of the hybrid system was evidenced by the MTT, hemolysis, dynamic clotting time, and zebrafish embryotoxicity tests. Last but not least, the hybrid system displayed outstanding long-lasting antimicrobial activity as shown by co-culture with Monoclonal <em>S. aureus</em>, thus suggesting great potential for applications in bacterial infection treatment.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 3","pages":"Pages 1563-1571"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007140","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":"Research on an effective, accurate, and universally applicable method for dual-loaded liposomes encapsulation efficiency","authors":"Tong Yuan ,&nbsp;Yuqi Zhu ,&nbsp;Yaqi Dai ,&nbsp;Fulin Bi ,&nbsp;Yan Lin ,&nbsp;Jin Yang","doi":"10.1016/j.xphs.2025.01.026","DOIUrl":"10.1016/j.xphs.2025.01.026","url":null,"abstract":"<div><h3>Objective</h3><div>Dual-loaded liposomes have become increasingly popular in the field of liposomal research. The encapsulation rate of dual-loaded drugs is an important indicator of the quality and efficacy of the dual-loaded liposomes. But it is difficult to determine the encapsulation efficiency of two drugs using a single method when the physicochemical properties of the drugs differ significantly. The aim of this study is to identify a method that is suitable for the different physicochemical properties of drugs and that efficiently and accurately determines the encapsulation efficiency of the two drugs in dual-loaded liposomes.</div></div><div><h3>Methods</h3><div>This study uses three different types of dual-loaded liposomes that simultaneously encapsulate lipophilic and hydrophilic drugs to examine the separation efficiency, encapsulation rate error, and applicability of various currently available methods for determining the encapsulation efficiency of dual-loaded liposomes. These methods include centrifugation, dialysis, ultrafiltration, microcolumn centrifugation, nanoparticle exclusion chromatography (nPEC), and polyethylene glycol-single-chain variable fragment (PEG-scFv) induced sedimentation.</div></div><div><h3>Results</h3><div>The results indicate that microcolumn centrifugation, nPEC, and PEG-scFv induced sedimentation methods achieved &gt;90 % separation efficiency for both lipophilic and hydrophilic drugs. Among these, microcolumn centrifugation is cumbersome to operate, and the PEG-scFv induced sedimentation method is only applicable to PEGylated liposomes. In contrast, the nPEC method requires no pre-treatment and is suitable for the separation of all nanoparticles and free drugs.</div></div><div><h3>Conclusions</h3><div>This study concludes through a comparative analysis that the nPEC method is an effective, accurate, and universally applicable method for assessing the encapsulation efficiency of dual-loaded liposomes.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 3","pages":"Pages 1583-1596"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073222","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":"Low voltage electron microscopy: An emerging tool for AAV characterization","authors":"Kevin D. Ausman ,&nbsp;Neal Whitaker ,&nbsp;Madhumitha Balasubramanian ,&nbsp;Bashkim Kokona ,&nbsp;Austin Vogt ,&nbsp;Sambit R. Kar","doi":"10.1016/j.xphs.2025.01.013","DOIUrl":"10.1016/j.xphs.2025.01.013","url":null,"abstract":"<div><div>Transmission electron microscopy has become a standard characterization tool for adeno-associated virus-based gene therapy products. However, cost and expertise requirements place in-house traditional transmission electron microscope systems out of reach for many companies in the field. Recently developed low voltage electron microscopes can fulfill many of the needs for adeno-associated virus characterization at a fraction of the cost. Example applications are discussed, including empty/full analysis, broken/incomplete capsid identification, and aggregate/high-molecular-weight species characterization. Our low voltage electron microscopy empty/full analysis agrees with orthogonal methods widely used in industry. Furthermore, analysis of broken/incomplete capsid morphologies using traditional transmission electron microscopy and low voltage electron microscopy shed light on a plausible mechanism for incomplete capsid aggregation that involves mutual passivation of open edges. A comprehensive analysis of AAV preparations using low voltage electron microscopy has been established.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 3","pages":"Pages 1554-1562"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066168","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":"2025 Editorial Advisory Board (EAB) appointments","authors":"Kenneth L. Audus","doi":"10.1016/j.xphs.2024.12.016","DOIUrl":"10.1016/j.xphs.2024.12.016","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 3","pages":"Page 1534"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895634","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(25)00162-5","DOIUrl":"10.1016/S0022-3549(25)00162-5","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 3","pages":"Pages A2-A4"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551229","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":"Current industry practices on closed system drug-transfer devices for parenteral drug products","authors":"Isabella de Jong ,&nbsp;David Cheng Thiam Tan ,&nbsp;Christian Lehermayr ,&nbsp;Mollie Daugherty ,&nbsp;Vasco Filipe ,&nbsp;Matthias Winzer ,&nbsp;Stanley C. Kwok ,&nbsp;Annette Medina ,&nbsp;Allison Guy ,&nbsp;Twinkle Christian ,&nbsp;Shubhadra N. Singh ,&nbsp;Soumendu Bhattacharya ,&nbsp;Serene Jabary","doi":"10.1016/j.xphs.2025.01.019","DOIUrl":"10.1016/j.xphs.2025.01.019","url":null,"abstract":"<div><div>USP&lt;800&gt; and NIOSH provide guidance on the use of Closed System Drug-Transfer Devices for hazardous drug in the healthcare setting. However, CSTDs are used by clinical sites irrespective of drug hazard status. In this paper, previous publications that describe evaluation and CSTD risk assessment strategies are presented. In addition, a pharmaceutical industry survey was performed to describe the current strategies for evaluation of CSTDs and how these devices are managed for clinical studies. Finally, recommendations are proposed to mitigate risks associated with CSTDs. These recommendations incorporate: testing considerations, risk assessments, and communication.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 3","pages":"Pages 1535-1547"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074872","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":"Centrifuge siliconization of primary container systems","authors":"Brian Wong ,&nbsp;Kaitlin Wang ,&nbsp;Kavin Kowsari,&nbsp;Yongchao Su,&nbsp;William Forrest,&nbsp;Jeffrey Givand,&nbsp;Guangli Hu","doi":"10.1016/j.xphs.2025.01.025","DOIUrl":"10.1016/j.xphs.2025.01.025","url":null,"abstract":"<div><div>Pre-filled syringes (PFS) have been in use in the pharmaceutical industry for over 60 years. For syringe functionality, a layer of silicone oil is often added as lubrication to promote smooth plunger stopper movement. Importantly, current technologies that generate this silicone oil layer often produce inhomogeneous layers displaying topographical features such as dimples. Additionally, the equipment that generates these layers is generally inaccessible in non-commercial settings. Here, we present a new silicone oil coating technique that addresses the shortcomings of traditional methods to generate a uniform silicone oil layer utilizing commonplace centrifuge technology. Our method creates silicone layers in PFS with improved homogeneity and tunable thickness, ranging from 400–1800 nm, by adjusting centrifuge speed and temperature.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 3","pages":"Pages 1548-1553"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074870","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":"2025 Scientific Advisors to the Editors (SAEs) appointments","authors":"Kenneth L. Audus","doi":"10.1016/j.xphs.2024.12.015","DOIUrl":"10.1016/j.xphs.2024.12.015","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 3","pages":"Page 1533"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895635","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}