Pharmaceutical Research最新文献

{"title":"Long-lasting Inhibition of L-type Amino Acid Transporter 1 by Nanvuranlat is Associated with Prolonged Cellular Retention Counteracted by Cancer-type OATP1B3 in Cholangiocarcinoma Cells.","authors":"Kiyoshi Oka, Yusuke Masuo, Atsunosuke Yamada, Tokiko Suzuki, Kazuo Sekiguchi, Masuhiro Yoshitake, Yukio Kato","doi":"10.1007/s11095-026-04223-z","DOIUrl":"https://doi.org/10.1007/s11095-026-04223-z","url":null,"abstract":"<p><strong>Purpose: </strong>Nanvuranlat (JPH203, NVL) is a selective L-type amino acid transporter 1 (LAT1) inhibitor that shows antitumor activity despite rapidly declining blood concentrations. This study investigated whether its long-lasting inhibition of LAT1 is associated with its cellular retention in HuCCT-1 cells, a human cholangiocarcinoma cell line.</p><p><strong>Methods: </strong>After NVL exposure and washout, LAT1 activity was evaluated by [¹⁴C]leucine uptake, and cell-associated NVL was quantified. The role of cancer-type OATP1B3 (Ct-OATP1B3) was examined using siRNA-mediated knockdown. Tumor retention was assessed in mice bearing HuCCT-1 xenografts.</p><p><strong>Results: </strong>Following preincubation with 100 µM NVL and a 4-h washout, [¹⁴C]leucine uptake was 60.4% of control. Cell-associated NVL amounts were negatively correlated with [¹⁴C]leucine uptake in preincubation and washout experiments, suggesting that retained NVL contributes to long-lasting LAT1 inhibition. Ct-OATP1B3 knockdown increased NVL retention after washout and enhanced LAT1 inhibition without affecting initial accumulation. In HuCCT-1 xenografts mice, NVL was retained in tumor tissue despite a rapid decline in plasma concentrations after intravenous administration.</p><p><strong>Conclusions: </strong>Prolonged cellular retention of NVL contributes to long-lasting LAT1 inhibition in HuCCT-1 cells. Tumor retention of NVL may partly explain the discrepancy between plasma exposure and antitumor efficacy. Ct-OATP1B3 may modulate NVL retention and sustained pharmacological activity in HuCCT-1 cells.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196145","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":"Development of a Mechanistic Distribution Model for Predicting Drug Partitioning into Human Milk.","authors":"Neel Deferm, Anna Murphy, Iain Gardner, Khaled Abduljalil","doi":"10.1007/s11095-026-04212-2","DOIUrl":"https://doi.org/10.1007/s11095-026-04212-2","url":null,"abstract":"<p><strong>Purpose/objective: </strong>Limited clinical data on drug safety during lactation complicate benefit-risk assessment for breastfeeding women who require pharmacotherapy. Mechanistic prediction of the milk-to-plasma ratio within physiologically-based pharmacokinetic frameworks offers a complementary and efficient approach to traditional clinical lactation studies. We aimed to develop a mechanistic milk partitioning model for milk-to-plasma ratio prediction that explicitly accounts for protein binding, pH-dependent ionization, lipid partitioning, electrostatic interactions with acidic phospholipids present in milk fat globule membranes, and membrane potential effects on drug disposition.</p><p><strong>Methods: </strong>Model performance was compared with both the phase distribution model and its log-transformed variant using a verification dataset of 107 observations from 57 compounds with diverse physicochemical properties.</p><p><strong>Results: </strong>For acids, moderate-to-strong bases and ampholytes, the milk partitioning model demonstrated the best performance (absolute average fold error (AAFE): 1.99, 1.70 and 3.34), outperforming both comparator models. For weak bases, the milk partitioning model achieved comparable accuracy to the phase distribution model and its log-transformed variant (AAFE: 1.63 vs. 1.62 and 1.64) while showing lower bias (average fold error (AFE): 0.92 vs. 0.72 and 0.73). Finally, for neutral compounds, the phase distribution model showed superior performance to the milk partitioning model (AAFE: 2.35 vs. 2.60).</p><p><strong>Conclusions: </strong>When integrated within a physiologically-based pharmacokinetic framework, the milk partitioning model provides a mechanistically robust and practical tool to support quantitative assessment of drug transfer into human milk and inform safer dosing strategies for breastfeeding populations.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168568","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":"Molecular Recognition and Immunopharmacological Implications of Serratiopeptidase Targeting Snake Venom Bradykinin-Potentiating Peptides.","authors":"Ankita Dhiman, Rahul Singh, Rituraj Purohit","doi":"10.1007/s11095-026-04222-0","DOIUrl":"https://doi.org/10.1007/s11095-026-04222-0","url":null,"abstract":"<p><strong>Purpose: </strong>Bradykinin-potentiating peptides (BPPs), found in snake venom, are known to modulate cardiovascular functions, but their susceptibility to enzymatic degradation remains poorly understood.</p><p><strong>Methods: </strong>Models were generated using AlphaFold-Colab for five small BPPs (< 9 amino acids) that did not have experimentally solved structures, and those BPPs which had reliable predictions of structure (pLDDT > 80) were used for docking studies. Protein-peptide docking experiments were done using HADDOCK for studying the interaction between wild-type (WT) and mutant serratiopeptidase with BPPs. After selecting the best complex, simulation of the complex was done using molecular dynamics (MD) simulations for 100 ns and binding energy determination using MM/PBSA analysis. For checking the mechanical stability of the protein-peptide complexes, Steered MD was performed.</p><p><strong>Results: </strong>HADDOCK docking identified BPP-4 as a favorable binder of WT and mutant serratiopeptidase supported by a HADDOCK score of -109.1 ± 5.2 and minimal restraint violations. MD simulations revealed greater stability in the mutant complex supported by persistent hydrogen bonds, reduced RMSD/RMSF fluctuations, restricted conformational sampling in PCA, favorable MM/PBSA energy contributions, and a more stable conformational ensemble in cluster analysis. The Steered MD simulation showed a higher rupture force in the mutant BPP-4-serratiopeptidase complex compared to the WT.</p><p><strong>Conclusions: </strong>Computational analysis identified BPP-4 as a promising serratiopeptidase-binding peptide, with differences in binding affinity and mechanical stability between WT and mutant complexes. The results offer insight into BPP-serratiopeptidase recognition at the molecular level and set the basis for future experiments on peptide binding.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168213","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":"Screening of Unexplored FDA-approved Inactive Ingredients as Stabilizers for Monoclonal Antibody Products.","authors":"Divya Agrawal, Charu Mittal, Avinash Mishra, Anurag S Rathore","doi":"10.1007/s11095-026-04221-1","DOIUrl":"https://doi.org/10.1007/s11095-026-04221-1","url":null,"abstract":"<p><strong>Purpose: </strong>Monoclonal antibodies (mAbs) are susceptible to physical and chemical degradation, which can compromise product quality, efficacy, safety, and shelf life. Although excipients play a critical role in stabilizing mAb formulations, only a limited number are routinely used in marketed products. Therefore, this study aimed to identify underexplored FDA-approved inactive ingredients with the potential to stabilize mAb formulations.</p><p><strong>Methods: </strong>Fourteen FDA-approved inactive ingredients were screened using a size-exclusion chromatography (SEC)-based comparative forced-degradation approach. Trastuzumab was used as the model IgG1 antibody and subjected to thermal stress at 70°C and 65°C. Candidate excipients were evaluated through concentration optimization, SEC-HPLC, fluorescence spectroscopy, UV-vis spectroscopy, differential scanning calorimetry, surface plasmon resonance, haemolysis assays, and molecular docking.</p><p><strong>Results: </strong>Initial screening identified isomalt and myo-inositol as the most effective excipients, reducing high-molecular-weight species by up to 60%, whereas choline chloride produced a smaller but measurable reduction. Optimized concentrations of 400 mM isomalt, 150 mM myo-inositol, and 1.9 mM choline chloride reduced aggregation, preserved monomer content, and improved higher-order structural stability. These formulations retained HER2 and FcRn binding and exhibited haemolysis below 3% compared to PS80 containing mAb sample. Isomalt also improved the thermal stability of adalimumab and rituximab, while molecular docking suggested preferential association with aggregation-prone regions of the trastuzumab Fab domain.</p><p><strong>Conclusions: </strong>Underexplored FDA-approved excipients, particularly isomalt and myo-inositol, improved mAb stability under thermal stress and represent promising candidates for further evaluation during therapeutic antibody formulation development.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164427","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 Hierarchical Dual-barrier Nanoparticle System Combining Solid Lipid Nanoparticles and Enteric Coating for Effective Oral Insulin Delivery.","authors":"Xinyi Che, Jingxin Gou, Xing Tang, Haibing He","doi":"10.1007/s11095-026-04224-y","DOIUrl":"https://doi.org/10.1007/s11095-026-04224-y","url":null,"abstract":"<p><strong>Objective: </strong>Oral delivery of insulin is limited by enzymatic degradation and instability in the gastrointestinal tract, as well as inefficient intestinal absorption. This study aimed to develop a dual-barrier oral insulin delivery system to protect insulin during gastrointestinal transit.</p><p><strong>Methods: </strong>A hierarchical formulation was constructed by integrating dextran-mediated insulin stabilization, solid lipid nanoparticle (SLN) encapsulation, enteric coating, and lyophilization. Insulin was first complexed with dextran and subsequently encapsulated into solid lipid nanoparticles (INS-SLNs) via a double-emulsion solvent evaporation method, followed by coating with Eudragit L100 (INS-SLNs-L100). The physicochemical properties, secondary structure, in vitro release and enzymatic stability, and in vivo hypoglycemic effects were evaluated.</p><p><strong>Results: </strong>The optimized INS-SLNs and INS-SLNs-L100 exhibited particle sizes of 221.2 ± 3.2 nm and 288.2 ± 1.1 nm, respectively, with encapsulation efficiencies exceeding 85%. The secondary structure of insulin was largely preserved after formulation and lyophilization. Both formulations improved the resistance of insulin to enzymatic degradation. The L100-coated formulation further enhanced insulin protection under simulated gastric conditions while maintaining efficient release under intestinal conditions. In streptozotocin-induced diabetic rats, oral administration resulted in relative pharmacological availability (rPA) values of 5.69% and 7.66% for INS-SLNs and INS-SLNs-L100, respectively, compared with 1.1% for oral insulin solution.</p><p><strong>Conclusion: </strong>The developed dual-barrier oral insulin delivery system provided enhanced gastrointestinal protection and sustained hypoglycemic effects after oral administration, supporting its potential as a formulation strategy for oral delivery of insulin and other peptide therapeutics.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168658","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":"Correction: Quantification of Unencapsulated Drug in Target Tissues Demonstrates Pharmacological Properties and Therapeutic Effects of Liposomal Topotecan (FF-10850).","authors":"Toshifumi Kimura, Ken Okada, Yasushi Morohashi, Shun Matsuda, Yukio Kato, Mikinaga Mori, Hiroshi Kato, Takeshi Matsumoto, Susumu Shimoyama","doi":"10.1007/s11095-026-04193-2","DOIUrl":"https://doi.org/10.1007/s11095-026-04193-2","url":null,"abstract":"","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138030","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":"Evaluating the Antimicrobial Activity of Curcumin-loaded Lipid Nanocarriers When Applying Photodynamic and Sonodynamic Therapy for the Treatment of Skin Infections.","authors":"Omar Molina-Alejandre, Angélica Villanueva-Martínez, María Guadalupe Nava-Arzaluz, Laura Abril Pérez-Carranza, Andrea Becerril-Osnaya, Gonzalo Hedain López-Mera, Raúl Dalí Cruz-Morales, Alma Alejandra Luna-Gómez, Doris Cerecedo, Ivette Martínez-Vieyra, María Andrea Trejo-Márquez, Selene Pascual-Bustamante, Yolanda I Chirino, Octavio Ispanixtlahuatl-Meraz, Adriana Ganem-Rondero","doi":"10.1007/s11095-026-04138-9","DOIUrl":"https://doi.org/10.1007/s11095-026-04138-9","url":null,"abstract":"<p><strong>Purpose: </strong>The antimicrobial activity of curcumin is the focus of this article, which sought to enhance it by formulating curcumin in lipid nanocarriers, and by applying Sonodynamic Therapy (ST) and Photodynamic Therapy (PT).</p><p><strong>Methodology: </strong>Curcumin-loaded lipid nanocarriers were formulated and characterized for size, zeta potential, morphology, FTIR, and DSC. The performance of the formulation was evaluated using antioxidant activity assays, in vitro release assays, occlusion assays, and stability assays under various conditions. The distribution of curcumin in pig skin in vitro was assessed using permeability assays and visualized by confocal microscopy. The antimicrobial activity was assessed against Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, applying PT or ST under different conditions. The cytotoxicity of the formulation was evaluated using HaCaT cells.</p><p><strong>Results and discussion: </strong>The curcumin-loaded lipid nanocarriers had a size of 63 nm, a polydispersity index of 0.202, a zeta potential of -41 mV, and an encapsulation efficiency > 95%. The properties of curcumin were enhanced by the lipid nanocarrier formulation, including stability, antioxidant activity, and skin-penetrating capacity. The antimicrobial activity of the formulation against the two strains was very low when combined with PT (< 12%), whereas ST achieved complete inhibition of P. aeruginosa. HaCaT viability was unaffected by the formulation or light.</p><p><strong>Conclusions: </strong>The proposed formulation may be a promising alternative for improving curcumin properties, preserving its stability, and enhancing its antimicrobial activity, particularly when combined with ST.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128209","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":"Polar vs Non-polar Excipients in BSA Aggregation.","authors":"Samuel Tien, Simone Nørgaard Krabbe, Annika Sollann Sørensen, Thomas Balle, Veysel Kayser","doi":"10.1007/s11095-026-04204-2","DOIUrl":"https://doi.org/10.1007/s11095-026-04204-2","url":null,"abstract":"<p><strong>Purpose: </strong>In recent years, there has been a rapid expansion in the development of new protein therapeutics in the pharmaceutical industry. Problematically, proteins are conformationally and colloidally marginally stable, and thus it is necessary to formulate them using buffering and stabilizing agents.</p><p><strong>Methods: </strong>In this study, we use experimental and computation techniques to evaluate the aggregation pathway, as well as the stabilizing properties of a range of excipients on a model protein; bovine serum albumin (BSA).</p><p><strong>Results: </strong>Our results show that polar excipients (L-arginine and trimethylamine N-oxide) decrease BSA stability, whereas non-polar excipients (L-alanine and L-valine) enhances it. To elucidate molecular mechanisms behind these trends, we constructed a multi-step unfolding and aggregation model. Upon thermal stress, the protein system is driven to form a disrupted dimer/trimer species across a steep activation energy barrier. This acts as the primary kinetic bottleneck, as once these intermediate states form sufficiently, large aggregates in tetramers and pentamers form across a significantly lower energy barrier. High temperature molecular dynamics simulations reveal that the unfolding mode of the monomer is characterized by the detachment of its C-terminus domain, creating an extended, aggregation prone structure. Crucially, in the native structure, this flexible region contains the only prominent solvent exposed hydrophobic patch on an otherwise hydrophilic protein surface. Therefore, hydrophobic excipients are predicted to interface with this hotspot, stabilizing the folded structure and suppressing downstream aggregation formation.</p><p><strong>Conclusions: </strong>Overall, this work demonstrates that understanding the specific protein aggregation mechanisms is key for the rational selection of stabilizers.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128199","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":"Triazavirin And Its Derivatives Act As Influenza A Virus Fusion Inhibitors.","authors":"Zaret G Denieva, Egor S Bulavko, Eva V Bersneva, Konstantin V Savateev, Alisa N Kozitsina, Vladimir L Rusinov, Oleg V Batishchev","doi":"10.1007/s11095-026-04216-y","DOIUrl":"https://doi.org/10.1007/s11095-026-04216-y","url":null,"abstract":"<p><strong>Purpose: </strong>The influenza A virus still remains one of the most dangerous pathogens possessing a high potential for the emergence of pandemic strains. However, there are only a few antivirals which are still effective against this virus. So-called viral fusion inhibitors are considered as a relatively new class of such drugs with a high therapeutic potential.</p><p><strong>Methods: </strong>We combined a system for monitoring the fusion of individual virions with lipid membranes, molecular dynamics simulations and measurements of affinity of charged molecules to lipid membranes. This allowed us to determine the mechanism of action of the antiviral drug.</p><p><strong>Results: </strong>We demonstrated that the additional mode of activity of triazavirin, the azoloazine derivative, passed clinical trials, can be an inhibition of the hemagglutinin of the influenza A virus. Combining experimental and computer approaches, we report a more effective modification of the target molecule than the registered drug triazavirin. Additionally, we suggested screening system, which has a good potential for studying the fusion activity and its inhibition for other viruses and potential antiviral drugs acting on viral fusion proteins.</p><p><strong>Conclusions: </strong>We report here triazavirin as a fusion inhibitor and propose a new molecule with high activity against influenza A virus, surpassing those of the triazavirin.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113627","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":"Critical Quality Attributes of Acyclovir Topical Creams: Characterization of Quality Attributes with Relevance to Topical Bioavailability.","authors":"Muralikrishnan Angamuthu, Srinatha Anegunda, Srinath Rangappa, Abhijeet Maurya, Hashemnejad Sm, Santanu Kundu, Howard Maibach, Priyanka Ghosh, Sam G Raney, S Narasimha Murthy","doi":"10.1007/s11095-026-04165-6","DOIUrl":"10.1007/s11095-026-04165-6","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize the quality (Q3) attributes of selected acyclovir topical creams and evaluate their relationship with topical bioavailability, as determined by in vitro permeation testing (IVPT).</p><p><strong>Methods: </strong>The Q3 attributes of five commercially available acyclovir cream products were comprehensively characterized. The formulations were then evaluated using IVPT across human cadaver skin. The Q3 attributes of the reference listed drugs (RLDs) approved in the USA, UK, and Austria, and generic products approved in Austria were compared and correlated with their permeation profiles.</p><p><strong>Results: </strong>The rate and extent of acyclovir permeation were comparable among cream products with similar Q3 attributes. Conversely, formulations exhibiting differences in Q3 attributes demonstrated significantly different topical bioavailability. Overall, IVPT performance correlated well with differences in the Q3 attributes of the formulations.</p><p><strong>Conclusions: </strong>This study demonstrates a strong association between Q3 attributes and the topical bioavailability of acyclovir creams. Comparable Q3 attributes predicted comparable in vitro performance, whereas differences in Q3 attributes resulted in significantly different permeation profiles. These findings support the importance of comprehensive Q3 characterization as a critical component in the development and regulatory assessment of topical drug products.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113682","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}