European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"A unifying approach to drug-in-polymer solubility prediction: Streamlining experimental workflow and analysis","authors":"Bjarke Strøm Larsen ,&nbsp;Peter Meiland ,&nbsp;Eidan Tzdaka ,&nbsp;Ingunn Tho ,&nbsp;Thomas Rades","doi":"10.1016/j.ejpb.2024.114478","DOIUrl":"10.1016/j.ejpb.2024.114478","url":null,"abstract":"<div><p>This method paper describes currently used experimental methods to predict the drug-in-polymer solubility of amorphous solid dispersions and offers a combined approach for applying the <em>Melting-point-depression method</em>, the <em>Recrystallization method</em>, and the <em>Melting-and-mixing method</em>. It aims to describe and expand on the theoretical basis as well as the analytical methodology of the recently published <em>Melting-and-mixing method</em>. This solubility method relies on determining the relationship between drug loads and the enthalpy of melting and mixing of a crystalline drug in the presence of an amorphous polymer. This relationship is used to determine the soluble drug load of an amorphous solid dispersion from the recorded enthalpy of melting and mixing of the crystalline drug portion in a drug-polymer sample at equilibrium solubility. Due to the complex analytical methodology of the <em>Melting-and-mixing method</em>, a software solution called the <em>Glass Solution Companion app</em> was developed. Using this new tool, it is possible to calculate the predicted drug-in-polymer solubility and Flory-Huggins interaction parameter from experimental samples, as well as to generate the resulting solubility-temperature curve. This software can be used for calculations for all three experimental methods, which would be useful for comparing the applicability of the methods on a given drug-polymer system. Since it is difficult to predict the suitability of these drug-in-polymer solubility methods for a specific drug-polymer system <em>in silico</em>, some experimental investigation is necessary. By optimizing the experimental protocol, it is possible to collect data for the three experimental methods simultaneously for a specific drug-polymer system. These results can then be readily analyzed using the <em>Glass Solution Companion app</em> to find the most appropriate method for the drug-polymer system, and therefore, the most reliable drug-in-polymer solubility prediction.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"203 ","pages":"Article 114478"},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124003047/pdfft?md5=0dc41c456466d07409605e53503dbc86&pid=1-s2.0-S0939641124003047-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential of exosomes as a new therapeutic strategy for glioblastoma","authors":"Leonor Cunha Silva ,&nbsp;Francisco Branco ,&nbsp;Joana Cunha ,&nbsp;Carla Vitorino ,&nbsp;Célia Gomes ,&nbsp;Mylène A. Carrascal ,&nbsp;Amílcar Falcão ,&nbsp;Bruno Miguel Neves ,&nbsp;Maria Teresa Cruz","doi":"10.1016/j.ejpb.2024.114460","DOIUrl":"10.1016/j.ejpb.2024.114460","url":null,"abstract":"<div><p>Glioblastoma (GBM) stands for the most common and aggressive type of brain tumour in adults. It is highly invasive, which explains its short rate of survival. Little is known about its risk factors, and current therapy is still ineffective. Hence, efforts are underway to develop novel and effective treatment approaches against this type of cancer.</p><p>Exosomes are being explored as a promising strategy for conveying and delivering therapeutic cargo to GBM cells. They can fuse with the GBM cell membrane and, consequently, serve as delivery systems in this context. Due to their nanoscale size, exosomes can cross the blood–brain barrier (BBB), which constitutes a significant hurdle to most chemotherapeutic drugs used against GBM. They can subsequently inhibit oncogenes, activate tumour suppressor genes, induce immune responses, and control cell growth.</p><p>However, despite representing a promising tool for the treatment of GBM, further research and clinical studies regarding exosome biology, engineering, and clinical applications still need to be completed.</p><p>Here, we sought to review the application of exosomes in the treatment of GBM through an in-depth analysis of the scientific and clinical studies on the entire process, from the isolation and purification of exosomes to their design and transformation into anti-oncogenic drug delivery systems. Surface modification of exosomes to enhance BBB penetration and GBM-cell targeting is also a topic of discussion.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"203 ","pages":"Article 114460"},"PeriodicalIF":4.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124002868/pdfft?md5=f552ae56077815d7d8c8af4dac354329&pid=1-s2.0-S0939641124002868-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted colorectal cancer treatment: In vitro anti-cancer effects of carnosine nanoparticles supported by agar and magnetic iron oxide","authors":"Lan-Chi Hsieh ,&nbsp;Thai-Khuong Le ,&nbsp;Fang-Ci Hu ,&nbsp;Ya-Ting Chen ,&nbsp;Shuchen Hsieh ,&nbsp;Chih-Chung Wu ,&nbsp;Shu-Ling Hsieh","doi":"10.1016/j.ejpb.2024.114477","DOIUrl":"10.1016/j.ejpb.2024.114477","url":null,"abstract":"<div><p>The usage of peptides in the colorectal cancer (CRC) treatment promises to be a new anti-cancer therapy with improved treatment efficacy. Carnosine, a natural dipeptide molecule, has been demonstrated to be a potential anti-cancer drug. Nonetheless, it shows an exhibition of high-water solubility and is quickly degraded by carnosinase. Meanwhile, agar and magnetic iron oxide are the most used materials for drug delivery due to some of their advantages such as the low cost and the larger biocompatibility feature. The purpose of this study was to investigate the anti-cancer ability of agar-encapsulated carnosine nanoparticles (AgCa-NPs) and agar-encapsulated carnosine nanoparticles-coated magnetic iron oxide nanoparticles (AgCaN-MNPs) in human CRC cells, HCT-116. We evaluated the effects of AgCa-NPs and AgCaN-MNPs with a variety of concentrations (0, 5, 10, 15, 30, 40, or 50 mM) on HCT-116 cells after 72 h and 96 h by using MTT assay and observation cell morphology. We then analyzed the cell cycle progression and assessed the expression changes of genes related to apoptosis, autophagy, necroptosis, and angiogenesis after treatment for 96 h. The results showed that AgCa-NPs and AgCaN-MNPs <em>in vitro</em> study decreased HCT-116 cells viability. This effect was attributed to arrest of cell cycle, induction of programmed cell death, and suppression of angiogenesis by AgCa-NPs and AgCaN-MNPs. These findings revealed the antitumor efficacy of AgCa-NPs or AgCaN-MNPs for CRC treatment.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"203 ","pages":"Article 114477"},"PeriodicalIF":4.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142097990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-amorphous systems of sulfasalazine with matrine-type alkaloids: Enhanced solubility behaviors and synergistic therapeutic potential","authors":"Xin Chen ,&nbsp;Yirui Qin ,&nbsp;Lijun Wang ,&nbsp;Yujing Zhu ,&nbsp;Hailu Zhang ,&nbsp;Wenhu Liu ,&nbsp;Mei Zeng ,&nbsp;Qian Dai","doi":"10.1016/j.ejpb.2024.114475","DOIUrl":"10.1016/j.ejpb.2024.114475","url":null,"abstract":"<div><p>Sulfasalazine (SULF), a sulfonamide antibiotic, has been utilized in the treatment of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) since its discovery. However, its poor water solubility causes the high daily doses (1–––3 g) for patients, which may lead to the intolerable toxic and side effects for their lifelong treatment for RA and IBD. In this work, two water-soluble natural anti-inflammatory alkaloids, matrine (MAR) and sophoridine (SPD), were employed to construct the co-amorphous systems of SULF for addressing its solubility issue. These newly obtained co-amorphous forms of SULF were comprehensively characterized by powder X-ray diffraction (PXRD), temperature-modulated differential scanning calorimetry (mDSC), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). We also investigated their dissolution behavior, including powder dissolution, in vitro release, and intrinsic dissolution rate. Both co-amorphous systems exhibited superior dissolution performance compared to crystalline SULF. The underlying mechanism responsible for the enhanced dissolution behaviors in co-amorphous systems were also elucidated. These mechanisms include the inhibition of nucleation, complexation, increased hydrophilicity, and robust intermolecular interactions in aqueous solutions. Importantly, these co-amorphous systems demonstrated satisfactory physical stability under various storage conditions. Network pharmacological analysis was utilized to investigate the potential therapeutic targets of both co-amorphous systems against RA, revealing similar yet distinct multi-target synergistic therapeutic mechanisms in the treatment of this condition. Our study suggests these drug-drug co-amorphous systems hold promise for optimizing SULF dosage in the future and providing a potential drug combination strategy.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"203 ","pages":"Article 114475"},"PeriodicalIF":4.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142097991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of dual-crosslinked Pluronic F127/Chitosan injectable hydrogels incorporating graphene nanosystems for breast cancer photothermal therapy and antibacterial applications","authors":"Manuel R. Pouso ,&nbsp;Bruna L. Melo ,&nbsp;Joaquim J. Gonçalves ,&nbsp;António G. Mendonça ,&nbsp;Ilídio J. Correia ,&nbsp;Duarte de Melo-Diogo","doi":"10.1016/j.ejpb.2024.114476","DOIUrl":"10.1016/j.ejpb.2024.114476","url":null,"abstract":"<div><p>Nanomaterials with responsiveness to near-infrared light can mediate the photoablation of cancer cells with an exceptional spatio-temporal resolution. However, the therapeutic outcome of this modality is limited by the nanostructures’ poor tumor uptake. To address this bottleneck, it is appealing to develop injectable <em>in situ</em> forming hydrogels due to their capacity to perform a tumor-confined delivery of the nanomaterials with minimal off-target leakage. In particular, injectable <em>in situ</em> forming hydrogels based on Pluronic F127 have been emerging due to their FDA-approval status, biocompatibility, and thermosensitive sol–gel transition. Nevertheless, the application of Pluronic F127 hydrogels has been limited due to their fast dissociation in aqueous media. Such limitation may be addressed by combining the thermoresponsive sol–gel transition of Pluronic F127 with other polymers with crosslinking capabilities. In this work, a novel dual-crosslinked injectable <em>in situ</em> forming hydrogel based on Pluronic F127 (thermosensitive gelation) and Chitosan (ionotropic gelation in the presence of NaHCO₃), loaded with Dopamine-reduced graphene oxide (DOPA-rGO; photothermal nanoagent), was developed for application in breast cancer photothermal therapy. The dual-crosslinked hydrogel incorporating DOPA-rGO showed a good injectability (through 21 G needles), <em>in situ</em> gelation capacity and cytocompatibility (viability &gt; 73 %). As importantly, the dual-crosslinking improved the hydrogel’s porosity and prevented its premature degradation. After irradiation with near-infrared light, the dual-crosslinked hydrogel incorporating DOPA-rGO produced a photothermal heating (ΔT ≈ 22 °C) that reduced the breast cancer cells’ viability to just 32 %. In addition, this formulation also demonstrated a good antibacterial activity by reducing the viability of <em>S. aureus</em> and <em>E. coli</em> to 24 and 33 %, respectively. Overall, the dual-crosslinked hydrogel incorporating DOPA-rGO is a promising macroscale technology for breast cancer photothermal therapy and antimicrobial applications.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"203 ","pages":"Article 114476"},"PeriodicalIF":4.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124003023/pdfft?md5=3c7ef09ecce1b31c9422cd4539e90de7&pid=1-s2.0-S0939641124003023-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing type V deep eutectic solvents with antimalarial pharmaceutical ingredients","authors":"Gabriel Teixeira ,&nbsp;Paula Brandão ,&nbsp;Ana I.M.C. Lobo Ferreira ,&nbsp;Dinis O. Abranches ,&nbsp;Luís M.N.B.F. Santos ,&nbsp;Olga Ferreira ,&nbsp;João A.P. Coutinho","doi":"10.1016/j.ejpb.2024.114463","DOIUrl":"10.1016/j.ejpb.2024.114463","url":null,"abstract":"<div><p>This work studies the formation of deep eutectic solvents formed by one active pharmaceutical ingredient (quinine, pyrimethamine, or 2-phenylimidazopyridine) and a second component potentially acting as an excipient (betaine, choline chloride, tetramethylammonium chloride, thymol, menthol, gallic acid, vanillin, acetovanillone, 4-hydroxybenzaldehyde, syringaldehyde, propyl gallate, propylparaben, or butylated hydroxyanisole), aiming to address challenges regarding drug solubility, bioavailability, and permeability. A preliminary screening was carried out using the thermodynamic model COSMO-RS, narrowing down the search to three promising excipients (thymol, propyl gallate, and butylated hydroxyanisole). Nine solid–liquid equilibrium (SLE) phase diagrams were experimentally measured combining the three model drugs with the screened excipients, and using a combination of a visual melting method and differential scanning calorimetry. Negative deviations from thermodynamic ideality were observed in all nine systems. Furthermore, a total of four new cocrystals were found, with powder and single crystal X-ray diffraction techniques being employed to verify their unique diffraction patterns. In the thermodynamic modelling of the SLE diagrams, two COSMO-RS parametrizations (TZVP and TZVPD-FINE) were also applied, though neither consistently delivered a better description over the other.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"203 ","pages":"Article 114463"},"PeriodicalIF":4.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124002893/pdfft?md5=28089df7203b8cfb55029c414e4254e0&pid=1-s2.0-S0939641124002893-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transglutaminase-catalyzed covalent","authors":"Prisca Hamm ,&nbsp;Denise Beckmann ,&nbsp;Rafael Worschech ,&nbsp;Alexandra Braun ,&nbsp;Marcus Gutmann ,&nbsp;Adelheid Korb-Pap ,&nbsp;Tessa Lühmann ,&nbsp;Thomas Pap ,&nbsp;Lorenz Meinel","doi":"10.1016/j.ejpb.2024.114462","DOIUrl":"10.1016/j.ejpb.2024.114462","url":null,"abstract":"<div><p>Nature realizes protein and peptide depots by catalyzing covalent bonds with the <strong>e</strong>xtra<strong>c</strong>ellular <strong>m</strong>atrix (ECM) of tissues. We are translating this natural blueprint for the sustained delivery of a myostatin-inhibiting peptide (Anti-Myo), resulting in an enzyme depot established from injectable solutions. For that, we fused Anti-Myo to the D-domain of insulin-like growth factor I, a <strong>t</strong>rans<strong>g</strong>lutaminase (TG) substrate. TG catalyzed the covalent binding of the D-domain to ECM proteins, such as laminin and fibronectin, on bioengineered ECM and in mice. ECM decorated with Anti-Myo suppressed myostatin activity and pathway activation and reduced the differentiation of preconditioned bone marrow-derived macrophages into osteoclasts in vitro.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"203 ","pages":"Article 114462"},"PeriodicalIF":4.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124002881/pdfft?md5=2d348b334f8e48d4c0bb55a457cbc3b5&pid=1-s2.0-S0939641124002881-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-29a-laden extracellular vesicles efficiently induced apoptosis through autophagy blockage in HCC cells","authors":"Homeyra Seydi ,&nbsp;Kosar Nouri ,&nbsp;Bahare Shokouhian ,&nbsp;Abbas Piryaei ,&nbsp;Moustapha Hassan ,&nbsp;Marco Cordani ,&nbsp;Ali Zarrabi ,&nbsp;Faezeh Shekari ,&nbsp;Massoud Vosough","doi":"10.1016/j.ejpb.2024.114470","DOIUrl":"10.1016/j.ejpb.2024.114470","url":null,"abstract":"<div><h3>Background</h3><p>In spite of significant advancements in theraputic modalities for hepatocellular carcinoma (HCC), there is still a high annual mortality rate with a rising incidence. Major challenges in the HCC clinical managment are related to the development of therapy resistance, and evasion of tumor cells apoptosis which leading unsatisfactory outcomes in HCC patients. Previous investigations have shown that autophagy plays crucial role in contributing to drug resistance development in HCC. Although, miR-29a is known to counteract authophagy, increasing evidence revealed a down-regulation of miR-29a in HCC patients which correlates with poor prognosis. Beside, evidences showed that miR-29a serves as a negative regulator of autophagy in other cancers. In the current study, we aim to investigate the impact of miR-29a on the autophagy and apoptosis in HCC cells using extracellular vesicles (EVs) as a natural delivery system given their potential in the miRNA delivery both <em>in vitro</em> and <em>in vivo</em>.</p></div><div><h3>Method</h3><p>Human Wharton’s Jelly mesenchymal stromal cell-derived extracellular vesicles were lately isolated through 20,000 or 110,000 × g centrifugation (EV20K or EV110K, respectively), characterized by western blot (WB), scanning electron microscopy (SEM), and dynamic light scattering (DLS). miR-29a was subsequently loaded into these EVs and its loading efficiency was evaluated <em>via</em> RT-qPCR. Comprehensive <em>in vitro</em> and <em>in vivo</em> assessments were then performed on Huh-7 and HepG2 cell lines.</p></div><div><h3>Results</h3><p>EV20K-miR-29a treatment significantly induces cell apoptosis and reduces both cell proliferation and colony formation in Huh-7 and HepG2 cell lines. In addition, LC3-II/LC3-I ratio was increased while the expression of key autophagy regulators <em>TFEB</em> and <em>ATG9A</em> were downregulated by this treatment. These findings suggest an effective blockade of autophagy by EV20K-miR-29a leading to apoptosis in the HCC cell lines through concomitant targeting of critical mediators within each pathway.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"203 ","pages":"Article 114470"},"PeriodicalIF":4.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyaluronidase overcomes the extracellular matrix barrier to enhance local drug delivery","authors":"Jingru Zhao,&nbsp;Jing Chen,&nbsp;Changqing Li,&nbsp;Hong Xiang,&nbsp;Xiaoqing Miao","doi":"10.1016/j.ejpb.2024.114474","DOIUrl":"10.1016/j.ejpb.2024.114474","url":null,"abstract":"<div><p>The stratum corneum of the skin presents the initial barrier to transdermal penetration. The dense structure of the extracellular matrix (ECM) further impedes local drug dispersion. Hyaluronidase (HAase) is a key component for the degradation of glycosidic bonding sites in hyaluronic acid (HA) within the ECM to overcome this barrier and enhance drug dispersion. HAase activity is optimal at 37–45 °C and in the pH range 4.5–5.5. Numerous FDA-approved formulations are available for the clinical treatment of extravasation and other diseases. HAase combined with various new nanoformulations can markedly improve intradermal dispersion. By degrading HA to create tiny channels that reduce the ECM density, these small nanoformulations then use these channels to deliver drugs to deeper layers of the skin. This deep penetration may increase local drug concentration or facilitate penetration into the blood or lymphatic circulation. Based on the generalization of 114 studies from 2010 to 2024, this article summarizes the most recent strategies to overcome the HAase-based ECM barrier for local drug delivery, discusses opportunities and challenges in clinical applications, and provides references for the future development of HAase. In the future, HAase-assisted topical administration is necessary to achieve systemic effects and to standardize HAase application protocols.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"203 ","pages":"Article 114474"},"PeriodicalIF":4.4,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biopharmaceutical studies of a novel sedative sublingual lozenge based on glycine and tryptophan: A rationale for mucoadhesive agent selection","authors":"O.V. Vashchenko ,&nbsp;R. Ye. Brodskii ,&nbsp;I.O. Davydova ,&nbsp;P.V. Vashchenko ,&nbsp;O.I. Ivaniuk ,&nbsp;O.A. Ruban","doi":"10.1016/j.ejpb.2024.114469","DOIUrl":"10.1016/j.ejpb.2024.114469","url":null,"abstract":"<div><p>Effective sedative drugs are in great demand due to increasing incidence of nervous disorders. The present work was aimed to develop a novel sublingual sedative drug based on glycine and <em>L</em>-tryptophan amino acids. Carbopol and different hydroxypropyl methylcellulose species were alternatively tested as mucoadhesive agents intended to prolong tryptophan sublingual release time. A model lipid medium of fully hydrated <em>L</em>-α-dimyristoylphosphatidylcholine was used for optimal mucoadhesive agents selection. Simultaneous processes of drug release and diffusion in lipid medium were first investigated involving both experimental and theoretical approaches. Individual substances, their selected combinations as well as different drug formulations were consecutively examined. Application of kinetic differential scanning calorimetry method allowed us to reveal a number of specific drug-excipient effects. Lactose was found to essentially facilitate tryptophan release and provide its ability to get into the bloodstream simultaneously with glycine, which is necessary to achieve glycine-tryptophan synergism. Introduction of a mucoadhesive agent into the formulation was shown to change kinetics of drug-membrane interactions variously depending on viscosity grade. Among the mucoadhesive agents, hydroxypropyl methylcellulose species K4M and E4M were shown to further accelerate drug release, therefore they were selected as optimal. Thus, effectiveness of the novel sedative drug was provided by including some excipients, such as lactose and the selected mucoadhesive agent species. A dynamic mathematical model was developed properly describing release and diffusion in lipid medium of various drug substances. Our study clearly showed applicability of a lipid medium to meet challenges such as drug-excipient interactions and optimization of drug formulations.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"203 ","pages":"Article 114469"},"PeriodicalIF":4.4,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}