AAPS open最新文献

{"title":"Second-generation lectin microarray for high throughput glycan profiling of therapeutic antibodies.","authors":"Kayla Hess, Helena Yun, Shen Luo, Uriel Ortega-Rodriguez, Grace Henry Lunde, Sarah Rogstad, Lai-Xi Wang, Baolin Zhang","doi":"10.1186/s41120-026-00172-4","DOIUrl":"10.1186/s41120-026-00172-4","url":null,"abstract":"<p><p>N-linked glycosylation is a critical quality attribute of therapeutic monoclonal antibodies (mAbs), influencing efficacy, safety, and pharmacokinetics. Accurate and high-throughput glycan profiling is therefore critical for product quality and manufacturing consistency. Here, we evaluated a novel lectin microarray platform for the detection of glycan epitopes commonly present in therapeutic antibodies. To assess specificity and performance, a panel of anti-HER2 mAbs with uniform glycan structures was generated via chemoenzymatic glycoengineering. These antibodies were analyzed in parallel by lectin microarray profiling of intact antibodies and mass spectrometry-based characterization of released glycans. Results from both approaches were highly concordant, demonstrating the lectin microarray's semi-quantitative capability for accurate glycan profiling. Further studies confirmed the platform's dynamic range and intermediate precision. Evaluation with the adalimumab reference product and eight biosimilars further confirmed its utility as a complementary tool for therapeutic antibody characterization. Collectively, these findings established the lectin microarray as a robust, high-throughput method for glycan analysis in therapeutic antibody development.</p>","PeriodicalId":520495,"journal":{"name":"AAPS open","volume":"12 32","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drying stability and permeability advantages of amorphous drug nanoparticles.","authors":"Akshay Narula, Ajay Lale, Paroma Chakravarty, Na Li","doi":"10.1186/s41120-026-00185-z","DOIUrl":"10.1186/s41120-026-00185-z","url":null,"abstract":"<p><p>The objective of this study was to develop stable amorphous drug nanoparticles with high drug loading and bioavailability advantages to overcome the drug-loading limitations of conventional amorphous solid dispersion (ASD) formulations. Amorphous drug nanoparticles were prepared <i>via</i> liquid-liquid phase separation in solution using various stabilizers, and their stability upon thermal drying and subsequent re-dispersion was evaluated. Zein, a stabilizer partitioning in the nanoparticle core alongside the active, was found to be highly effective in stabilizing said nanoparticles upon thermal drying. In contrast, most other stabilizers categorized as \"wall materials\", required substantially higher amounts to achieve effective stabilization of the amorphous drug particles. Of these, the wall materials exhibiting ionic interactions with the drug, were found to markedly enhance nanoparticle stability during drying. Despite the use of stabilizers, nanoparticle drying stability varied with batch size, suggesting the need to consider the effects of both scale-up and process parameters for the development of this type of formulation. Subsequent membrane permeability studies with dried amorphous nanoparticles showed their membrane permeability to be comparable to that of fast-releasing ASDs. This phenomenon was found to be independent of drug-stabilizer ionic interactions in the nanoparticles. These results confirm amorphous drug nanoparticles to be an effective strategy for overcoming drug-loading constraints in ASD formulations without compromising bioavailability. Our results also provide insights into excipient-drug interactions and their impact on the drying stability of amorphous drug nanoparticles, which is critical for the development of stable, high drug-loading amorphous nanoparticle formulations.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1186/s41120-026-00185-z.</p>","PeriodicalId":520495,"journal":{"name":"AAPS open","volume":"12 1","pages":"46"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148595339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mastering particle size analysis: lessons, challenges, and future directions from the FDA-CRCG workshop.","authors":"Xiaoming Xu, William C Smith, James E Polli, Christine L Plavchak, Bin Qin, Yan Wang, Nicholas Holtgrewe, Sam G Raney, Andre O'Reilly Beringhs, Yihua Bruce Yu, Marc Taraban, Vishalakshi Krishnan, Anna Schwendeman, Dana C Hammell, Jeffrey D Clogston, Alan F Rawle, Jernej Grmaš, Yousif Ayoub, Bernard Domnic, Rama Subba Reddy, Joseph Duncan, Matthew McGann, Jeff Bodycomb, Carl C L Schuurmans, Michiel Hermes, Jonathan G Mehtala, Prashun Roy, Kevin Lance, Collin Britten, Kiwan Park, Daniel Beach, Matthew Elmer, Keith B Rodenhausen, Zhen Xu, Haiou Qu, Kai-Wei Wu, Maxwell Korang-Yeboah, Yuan Zou, Ji Li, Alaa H Abuznait, Colette Quinn, Anabelle Ethier, Kendice Ip, Dinesh Dhamecha, Qi Li, Dongkai Zhu, Rutu Valapil","doi":"10.1186/s41120-026-00148-4","DOIUrl":"10.1186/s41120-026-00148-4","url":null,"abstract":"<p><p>Particle-size distribution (PSD) measurement is a cornerstone of pharmaceutical development and regulatory assessment, influencing formulation stability, dissolution, product quality, and performance. Yet the seemingly straightforward nature of \"size measurements\" often conceals substantial scientific and practical complexity. To strengthen shared understanding and advance good measurement practices, the U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) co-hosted a two-day hybrid workshop, \"Mastering Particle Size Analysis: A Step-by-Step Illustration of Techniques and Best Practices,\" held on September 23-24, 2025. The workshop brought together scientists from regulatory agencies, industry, academia, and instrument manufacturers to examine the principles, data interpretation, and analytical procedure robustness of two widely used techniques-Dynamic Light Scattering (DLS) and Laser Diffraction (LD). The program integrated scientific lectures, vendor-led demonstrations, and structured small-group discussions organized around real-world case studies. Prior to the workshop, participating vendors conducted independent characterization of five pre-workshop materials representing diverse formulation types, providing a shared baseline for comparison. In total, 2823 participants registered for the workshop, including 127 for in-person attendance and 2696 for virtual attendance from across the global pharmaceutical community. Of those that registered, 119 participants attended in-person, and 1464 attended virtually during the two days. Discussions throughout the workshop emphasized that PSD data cannot be interpreted in isolation because what is measured depends on the model assumption, sample condition, and analytical purpose. Participants concluded that reliable characterization demands \"fit-for-purpose\" analytical procedure design, transparent reporting, and a clear linkage between measurements and material function. Major outcomes included (i) recognition that methodological transparency outweighs pursuit of a single \"true\" particle size; (ii) identification of the dominant sources of inter-laboratory variability; and (iii) broad consensus on the need for harmonized terminology, validation criteria, and reporting expectations. The workshop closed with collective commitments to prepare a community white paper and to initiate an inter-laboratory study aimed at improving comparability of PSD data across techniques, platforms, and laboratories-steps that will help ensure measurement integrity and regulatory confidence in complex drug development.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1186/s41120-026-00148-4.</p>","PeriodicalId":520495,"journal":{"name":"AAPS open","volume":"12 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning guided optimization of an oral microemulsion system: a Bayesian optimization approach.","authors":"Madeline Gunawardena, Bao Chau, Hayden Nothacker, Rudra Pangeni, Thomas Roper, Qingguo Xu, Charles McGill","doi":"10.1186/s41120-026-00176-0","DOIUrl":"10.1186/s41120-026-00176-0","url":null,"abstract":"<p><p>Oral microemulsions are one drug delivery system often implemented to improve intestinal permeability and oral bioavailability of poorly water-soluble drugs. They also present several practical advantages including high patient compliance and simplified manufacturing methods which contribute to their promise as marketable drug products. Despite these advantages, however, the microemulsion formulation development process is extremely time consuming and resource intensive, typically involving extensive screening of components and excessive preliminary trials in order to achieve stable formulations. As a result, MEs are often suboptimal in their therapeutic performance, and there is an unmet need for improved methods to streamline microemulsion formulation design. In this work, a batch Bayesian Optimization strategy was used to design a subset of unique in-specification microemulsions with highly optimized physicochemical properties in five iterations containing batches of five experiments. A two-phase modeling approach was developed to achieve this goal and allowed for navigating a complex experimental design space, including multiple oils, surfactants, cosurfactants, and processing parameters with an initial training dataset consisting of 22 experiments. As a result of this study, five high-performing blank microemulsions were identified, and four of them exhibited physical stability upon storage for up to 30 days. Further, when loaded with two different model drug candidates, three of the microemulsions achieved high drug loading, acceptable stability and improved in-vitro permeability, highlighting their promise for potential translation to later stages of development.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1186/s41120-026-00176-0.</p>","PeriodicalId":520495,"journal":{"name":"AAPS open","volume":"12 1","pages":"34"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13328243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic models with experimental comparison for microwave-assisted lyophilization in a vial.","authors":"Isaac S Wheeler, Ahmad Darwish, Vivek Narsimhan, Alina A Alexeenko","doi":"10.1186/s41120-026-00173-3","DOIUrl":"10.1186/s41120-026-00173-3","url":null,"abstract":"<p><p>Microwave heating has been shown to accelerate pharmaceutical lyophilization but robust process models, crucial to ensuring that the process is efficient without damaging products, are still scarce. Building on both high-frequency microwave lyophilization experiments and recent modeling efforts, we develop a 2D level set simulation which refines the assumptions made in lumped capacitance (LC) models. The 2D level set model is also capable of integrating information about measured porous structures and accounting for experimental observations where thermocouples are placed imperfectly. Of the 4 empirical parameters in the LC model, we remove one based on level set results and estimate two more by electromagnetic simulation, recommending a new variant of the 0D lumped capacitance model. This LC model is compared to experiments in both microwave-assisted lyophilization and microwave vacuum drying of products in vials, emphasizing that microwave heating of the vial wall and heat conduction from the vial wall to frozen product cannot be neglected. The implementations of the new models, alongside the analysis, are published as open source Julia code.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":520495,"journal":{"name":"AAPS open","volume":"12 1","pages":"42"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148407736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-time in vivo tracking of nanoparticulate vaccines in inguinal lymph nodes.","authors":"Bishal Misra, Kaitlyn M Landreth, William H Pentz, Tracy W Liu, Sharan Bobbala","doi":"10.1186/s41120-026-00163-5","DOIUrl":"10.1186/s41120-026-00163-5","url":null,"abstract":"<p><p>Understanding the kinetics of nanoparticle vaccine drainage to the lymph nodes and their residence time in these tissues is critical in vaccine development. Evaluating these parameters using conventional techniques is expensive, time-consuming, and often leads to variable data, as several animals at different time points need to be sacrificed, and lymph nodes need to be harvested for characterization. Here, we adapted an abdominal window chamber for intravital imaging of the lymph nodes, enabling real-time tracking of ionizable lipid nanoparticles (LNPs) and polymeric nanoparticles in live mice following intramuscular administration. To mimic delivery of vaccine payloads, these nanoparticles were encapsulated with luciferase mRNA or a small molecule fluorophore, indocyanine green, and tracked for bioluminescence and fluorescence, respectively, in the lymph nodes. The results demonstrated differential lymph node drainage kinetics and retention for LNPs and polymeric nanoparticles. Notably, variations in the ionizable lipid components of LNPs resulted in changes in the mRNA translation ability within the lymph nodes. Taken together, this study introduces a valuable tool to optimize nanoparticle vaccine design in preclinical studies.</p><p><strong>Graphical abstract: </strong>Real-time in vivo tracking of the lymph node drainage kinetics of nanoparticles encapsulating mRNA or small molecule fluorescent dye, facilitated by the use of a lymph node window chamber. Created in BioRender. https://BioRender.com/786dnai.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1186/s41120-026-00163-5.</p>","PeriodicalId":520495,"journal":{"name":"AAPS open","volume":"12 1","pages":"23"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent trends in pharmaceutical freeze-drying and control strategies observed in human drug applications and manufacturing inspections.","authors":"Steve Y Rhieu, Maxwell Korang-Yeboah, David D Anderson, John Arigo, Thomas O'Connor, Rakhi Shah","doi":"10.1186/s41120-025-00132-4","DOIUrl":"10.1186/s41120-025-00132-4","url":null,"abstract":"<p><p>Freeze-drying has been a workhorse for the pharmaceutical industry to enable long-term storage and long-distance transport of drug products that are unstable in liquid or frozen form. The importance of freeze-drying was particularly evident in the development and storage of life-saving medicines such as mRNA-based vaccines during the COVID-19 pandemic. In response to growing demand for improved manufacturing efficiency, emerging freeze-drying technologies spurred by the U.S. Food and Drug Administration (FDA) Pharmaceutical Quality for the 21st Century Initiative have been introduced with the aim to modernize the pharmaceutical manufacturing sector. Here, we provide regulatory considerations for emerging technologies in pharmaceutical freeze-drying from a manufacturing perspective. We also present an analysis of current trends in freeze-drying and in-process controls submitted in human drug applications-24 New Drug Applications, 118 Abbreviated New Drug Applications, and 20 Biologics License Applications assessed between 2020 and 2023-seeking FDA approval. Additionally, we analyzed the Form FDA-483 Inspection Observations educed from 201 inspections conducted at manufacturing facilities performing freeze-dried parenteral operations between 2015 and 2019, to identify common compliance challenges and provide regulatory insights for the pharmaceutical industry.</p>","PeriodicalId":520495,"journal":{"name":"AAPS open","volume":"11 ","pages":"27"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12930400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147314312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral delivery of the non-β-blocking R-carvedilol enantiomer for skin cancer chemoprevention in SKH-1 mice.","authors":"Pabitra K Sardar, Steven Yeung, Ruby Tow, Jacqueline Luga, Matthew Huang, Ayaz Shahid, Bradley T Andresen, Ying Huang","doi":"10.1186/s41120-024-00103-1","DOIUrl":"10.1186/s41120-024-00103-1","url":null,"abstract":"<p><strong>Purpose: </strong>Skin cancer remains the most prevalent cancer worldwide with its incidence continuously rising. Previous studies have demonstrated the efficacy of the β-blocker carvedilol and its non-β-blocking enantiomer R-carvedilol in mitigating UV-induced skin carcinogenesis through topical application. The current study investigated whether orally administered R-carvedilol could prevent the development of skin cancer in SKH-1 mice.</p><p><strong>Methods: </strong>Efficacy of orally delivered R-carvedilol was examined in SKH-1 mice exposed to repeated UV radiations for 25 weeks. Pharmacokinetic studies were conduced in mice to evaluate the drug levels in plasma and skin tissues. Pharmacodynamic studies were used to evaluate the effects of oral R-carvedilol and racemic carvedilol on mouse blood pressure.</p><p><strong>Results: </strong>The findings revealed a statistical difference in tumor incidence between the group receiving R-carvedilol (20 mg/kg) and the UV-only control group (<i>p</i> = 0.00860), while lower doses of R-carvedilol (1.5 mg/kg and 5 mg/kg) did not exhibit a significant impact on tumor incidence. While tumor multiplicity varied significantly between groups (<i>p</i> = 0.005325), tumor volume analysis showed no statistical difference. Pharmacokinetic studies indicated that R-carvedilol accumulated in a dose-dependent manner within plasma and skin tissues. Notably, at a dosage of 32 mg/kg, oral R-carvedilol did not influence blood pressure, in contrast to carvedilol, highlighting its potential for chemoprevention with minimal cardiovascular side effects.</p><p><strong>Conclusions: </strong>These data support oral administration of R-carvedilol as a viable strategy for the chemoprevention of skin cancer, given its efficacy and minimal impact on the cardiovascular system. Further studies determining the optimal doses and timing of drug treatment are warranted.</p>","PeriodicalId":520495,"journal":{"name":"AAPS open","volume":"11 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bardoxolone methyl improves survival and reduces clinical measures of kidney injury in tumor-bearing mice treated with cisplatin.","authors":"Lauren E Thompson, Stacey M Tuey, Paola Garcia Gonzalez, Carly S Chesterman, Courtney D McGinnis, M Scott Lucia, Lauren M Aleksunes, Charles L Edelstein, Melanie S Joy","doi":"10.1186/s41120-025-00107-5","DOIUrl":"10.1186/s41120-025-00107-5","url":null,"abstract":"<p><strong>Objective: </strong>Acute kidney injury (AKI) occurs in approximately one-third of patients treated with cisplatin and there is an outstanding need for mitigation strategies to decrease the frequency and severity of cisplatin-induced AKI. This study evaluated bardoxolone methyl (BARD) as a nephroprotectant in a multidose, tumor-bearing mouse model of cisplatin-induced AKI. BARD is an attractive therapeutic intervention due to its ability to protect against cisplatin-induced nephrotoxicity by activating Nrf2 and previous reports suggesting anti-tumorigenic effects.</p><p><strong>Methods: </strong>In this study, CMT167 tumor-bearing mice were treated with four weekly doses of cisplatin with or without BARD and evaluated for survival, tumor growth, and clinical and histological measures of AKI. Kidney injury and/or function were evaluated by quantification of urinary kidney injury molecule-1 (KIM-1) and serum creatinine (SCr) levels as well as histopathology.</p><p><strong>Results: </strong>Compared to mice receiving cisplatin alone, co-treatment with BARD significantly enhanced survival (<i>p</i> = 0.01). Moreover, BARD prevented elevation of urinary KIM-1 concentrations as early as one week after cisplatin treatment (<i>p</i> < 0.01) - a response that was observed throughout the 4-week study period. Cisplatin increased SCr concentrations by four weeks, which was prevented by BARD co-administration (<i>p</i> < 0.01). Cisplatin treatment significantly decreased tumor burden compared to vehicle-treated mice (<i>p</i> < 0.05 after two cisplatin doses) - a response that was not altered by BARD co-treatment.</p><p><strong>Conclusions: </strong>Overall, the results of this study demonstrate that BARD has the potential to improve survival and reduce clinical measures of kidney injury in tumor-bearing mice treated with cisplatin, suggesting it could be used as a nephroprotectant to mitigate cisplatin-induced AKI.</p>","PeriodicalId":520495,"journal":{"name":"AAPS open","volume":"11 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12387945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the impact of charge and hydrophilicity on peptide-mucin interactions using a simple mucin model.","authors":"Waleed M Elballa, Aiden Gregory, Teruna J Siahaan, Michael J Hageman","doi":"10.1186/s41120-025-00123-5","DOIUrl":"10.1186/s41120-025-00123-5","url":null,"abstract":"<p><p><i>In vitro</i> models used to investigate drug diffusion face certain limitations and challenges because they omit for mucus interactions that could influence diffusional transport. This study developed a simple mono-component mucin model using Mucin Type II from porcine stomach to predict the effects of the physicochemical properties of peptides on their diffusion through the intestinal mucus layer. The diffusion of octreotide and lanreotide through a mucin layer was compared with their respective Ala mutants replacing Lys (i.e., octreotide A5 and lanreotide A5). Ala mutants showed higher diffusion than their respective parent peptides, implicating that the charge interaction between positively charged, Lys-containing peptide and negative charge mucin override their hydrophobic interactions, thus hindering peptide diffusion. This finding was also supported by the faster diffusion of the negatively charged FITC-ADT10 compared to the positively charged FITC-HAV10 peptide. Thus, the interaction between the peptide's positive and the negative charge of the glycans in mucin hinders peptide diffusion.. The neutral DTPPVK has the highest hydrophilicity and diffusion compared to negatively charged DTPPD, DTPPT, and ADTC5. Although DTPPD and DTPPT have about the same hydrophilicity, DTPPD has better diffusion than DTPPT because DTPPD with -2 charges has higher negative charge repulsion against mucin compared to that of DTPPT with -1 charge. Finally, ADTC5, with the lowest hydrophilicity, has the lowest diffusion through the mucin layer. This study found that the charge and hydrophilicity of peptides influence their diffusion across the mucin layer, and these studies correlate with the previous studies utilizing different in vitro models.</p>","PeriodicalId":520495,"journal":{"name":"AAPS open","volume":"11 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12830042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}