Pharmaceutics最新文献

{"title":"Hydrogels and Nanogels: Pioneering the Future of Advanced Drug Delivery Systems.","authors":"Ernesto J Delgado-Pujol, Guillermo Martínez, David Casado-Jurado, Juan Vázquez, Jesús León-Barberena, David Rodríguez-Lucena, Yadir Torres, Ana Alcudia, Belén Begines","doi":"10.3390/pharmaceutics17020215","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020215","url":null,"abstract":"<p><p>Conventional drug delivery approaches, including tablets and capsules, often suffer from reduced therapeutic effectiveness, largely attributed to inadequate bioavailability and difficulties in ensuring patient adherence. These challenges have driven the development of advanced drug delivery systems (DDS), with hydrogels and especially nanogels emerging as promising materials to overcome these limitations. Hydrogels, with their biocompatibility, high water content, and stimuli-responsive properties, provide controlled and targeted drug release. This review explores the evolution, properties, and classifications of hydrogels versus nanogels and their applications in drug delivery, detailing synthesis methods, including chemical crosslinking, physical self-assembly, and advanced techniques such as microfluidics and 3D printing. It also examines drug-loading mechanisms (e.g., physical encapsulation and electrostatic interactions) and release strategies (e.g., diffusion, stimuli-responsive, and enzyme-triggered). These gels demonstrate significant advantages in addressing the limitations of traditional DDS, offering improved drug stability, sustained release, and high specificity. Their adaptability extends to various routes of administration, including topical, oral, and injectable forms, while emerging nanogels further enhance therapeutic targeting through nanoscale precision and stimuli responsiveness. Although hydrogels and nanogels have transformative potential in personalized medicine, challenges remain in scalable manufacturing, regulatory approval, and targeted delivery. Future strategies include integrating biosensors for real-time monitoring, developing dual-stimuli-responsive systems, and optimizing surface functionalization for specificity. These advancements aim to establish hydrogels and nanogels as cornerstones of next-generation therapeutic solutions, revolutionizing drug delivery, and paving the way for innovative, patient-centered treatments.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503294","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":"Prediction of Pharmacokinetics for CYP3A4-Metabolized Drugs in Pediatrics and Geriatrics Using Dynamic Age-Dependent Physiologically Based Pharmacokinetic Models.","authors":"Jing Han, Zexin Zhang, Xiaodong Liu, Hanyu Yang, Li Liu","doi":"10.3390/pharmaceutics17020214","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020214","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The use of medicines in pediatrics and geriatrics is widespread. However, information on pharmacokinetics of therapeutic drugs mainly comes from healthy adults, and the pharmacokinetic parameters of therapeutic drugs in other age stages, including pediatrics and geriatrics, are limited. The aim of the study was to develop a dynamic age-dependent physiologically based pharmacokinetic (PBPK) model to predict the pharmacokinetics of drugs in humans at different ages. <b>Method</b>: The PBPK models characterizing dynamic age-dependence were developed in adults (20-59 years old) and 1000 virtual individuals were constructed. Four CYP3A substrates, namely midazolam, fentanyl, alfentanil and sufentanil, served as model drugs. Following validation using clinic observations in adult populations, the developed PBPK models were extrapolated to other age populations, such as pediatrics and geriatrics, via replacing their physiological parameters and pharmacokinetic parameters, such as organ volume, organ blood flow, clearance, f_u,b and K_t:p. The simulations were compared with clinic observations in corresponding age populations. Midazolam served as an example, the dose transitions between adult pediatrics and adult geriatrics were visualized using the developed PBPK models. <b>Results</b>: Most of observed plasma concentrations fell within the 5th-95th percentile of the predicted values in the 1000 virtual individuals, and the predicted AUC_0-t and C_max were almost within between 0.5 and 2 times of the observations. The optimization of dosages in pediatrics and geriatrics were further documented. <b>Conclusions</b>: The developed PBPK model may be successfully used to predict the pharmacokinetics of CYP3A4-metabolized drugs in different age groups and to optimize their dosage regiments in pediatrics and geriatrics.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503321","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 Multivalent mRNA Therapeutic Vaccine Exhibits Breakthroughs in Immune Tolerance and Virological Suppression of HBV by Stably Presenting the Pre-S Antigen on the Cell Membrane.","authors":"Shang Liu, Jie Wang, Yunxuan Li, Muhan Wang, Pei Du, Zhijie Zhang, Wenguo Li, Rongchen Sun, Mingtao Fan, Meijia Yang, Hongping Yin","doi":"10.3390/pharmaceutics17020211","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020211","url":null,"abstract":"<p><p><b>Background/Objectives</b>: In chronic hepatitis B infection (CHB), the hepatitis B surface antigen (HBsAg) continuously exhausts the hepatitis B surface antibody (HBsAb), which leads to the formation of immune tolerance. Accordingly, the hepatitis B virus (HBV) infection can be blocked by inhibiting the binding of the hepatitis B surface pre-S1/pre-S2 antigen to the hepatocyte receptor NTCP, but the clinical cure rate of pre-S-based vaccines for CHB is limited. <b>Methods</b>: In this study, we designed and prepared multivalent hepatitis B therapeutic mRNA vaccines encoding three hepatitis B surface antigen proteins (L, M, and S) at the cell membrane, verified via in vitro transfection and expression experiments. An in vivo immunization experiment in HBV transgenic (Tg) mice was first completed. Subsequently, an adeno-associated virus plasmid vector carrying the HBV1.2-fold genome (pAAV HBV1.2) model and the adeno-associated virus vector carrying HBV1.3-fold genome (rAAV HBV1.3) model were constructed and immunized with mRNA vaccines. The HBV antigen, antibodies, and HBV DNA in serum were detected. Indirect (enzyme-linked immunosorbent assay) ELISA were made to analyze the activated antigen-specific IgG in HBV Tg mice. Antigen-dependent T-cell activation experiments were carried out, as well as the acute toxicity tests in mice. <b>Results</b>: The L protein/pre-S antigens could be stably presented at the cell membrane with the support of the S protein (and M protein). After vaccinations, the vaccines effectively reactivated the production of high levels of HBsAb, disrupted immune tolerance, and activated the production of high-affinity antibodies against structural pre-S antigen in HBV Tg mice. The HBsAg seroconversion and serum HBV DNA clearance were achieved in two HBV mice models. Furthermore, pre-S antigen-dependent T-cell response against HBV infection was confirmed. The therapeutic vaccine also showed safety in mice. <b>Conclusions</b>: A novel therapeutic mRNA vaccine was developed to break through HBsAg-mediated immune tolerance and treat CHB by stably presenting the pre-S antigen at the membrane, and the vaccine has great potential for the functional cure of CHB.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503262","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":"Cancer Vaccines and Beyond: The Transformative Role of Nanotechnology in Immunotherapy.","authors":"Violeta Delgado-Almenta, Jose L Blaya-Cánovas, Jesús Calahorra, Araceli López-Tejada, Carmen Griñán-Lisón, Sergio Granados-Principal","doi":"10.3390/pharmaceutics17020216","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020216","url":null,"abstract":"<p><p>Cancer is one of the leading causes of morbidity and mortality globally, responsible for approximately 10 million deaths in 2022 and an estimated 21 million new cases in 2024. Traditional cancer treatments such as surgery, radiation therapy, and chemotherapy often present limitations in efficacy and side effects. However, immunotherapeutic vaccines have emerged as a promising approach, leveraging the body's immune system to target and eliminate cancer cells. This review examines the evolving landscape of cancer vaccines, differentiating between preventive and therapeutic strategies and highlighting the significance of tumor-specific antigens, including tumor-associated antigens (TAAs) and neoantigens. Recent advancements in vaccine technology, particularly through nanotechnology, have resulted in the development of nanovaccines, which enhance antigen stability, optimize delivery to immune cells, and promote robust immune responses. Notably, clinical data indicate that patients receiving immune checkpoint inhibitors can achieve overall survival rates of approximately 34.8 months compared to just 15.7 months for traditional therapies. Despite these advancements, challenges remain, such as the immunosuppressive tumor microenvironment and tumor heterogeneity. Emerging evidence suggests that combining nanovaccines with immunomodulators may enhance therapeutic efficacy by overcoming these obstacles. Continued research and interdisciplinary collaboration will be essential to fully exploit the promise of nanovaccines, ultimately leading to more effective and accessible treatments for cancer patients. The future of cancer immunotherapy appears increasingly hopeful as these innovative strategies pave the way for enhanced patient outcomes and an improved quality of life in oncology.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503186","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":"Riboflavin-Mediated Photodynamic Therapy in Periodontology: A Systematic Review of Applications and Outcomes.","authors":"Jakub Fiegler-Rudol, Maciej Łopaciński, Artur Los, Dariusz Skaba, Rafał Wiench","doi":"10.3390/pharmaceutics17020217","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020217","url":null,"abstract":"<p><p><b>Background</b>: Riboflavin (vitamin B₂) has emerged as a promising photosensitizer in photodynamic therapy (PDT) due to its strong absorption of blue light and favourable safety profile. This systematic review aims to evaluate the efficacy of riboflavin-mediated PDT in periodontology, specifically examining its antimicrobial effects and potential to improve clinical outcomes compared to conventional or other PDT-based treatments. <b>Methods</b>: A systematic review was conducted following PRISMA guidelines. A comprehensive literature search was performed in PubMed/Medline, Embase, Scopus, and the Cochrane Library. Studies published in English within the last 10 years were considered, where riboflavin served as the primary photosensitizer for dental treatments. Data extraction focused on study design, photosensitizer concentration, light source parameters, and clinical or microbiological outcomes. The risk of bias was assessed independently by two reviewers using a predefined scoring system. <b>Results</b>: Ten studies met the inclusion criteria, all demonstrating a low risk of bias. Riboflavin-mediated PDT consistently reduced microbial biofilms and pathogen viability in periodontitis, peri-implantitis, and endodontic models. Although some studies reported slightly lower efficacy compared to chlorhexidine or toluidine blue-based PDT, riboflavin-mediated PDT exhibited advantages such as minimal staining, low cytotoxicity, and enhanced collagen crosslinking. However, most studies were in vitro or small-scale clinical trials, limiting conclusions on long-term effectiveness. <b>Conclusions</b>: Riboflavin-mediated PDT shows promise as a safe adjunctive therapy for periodontal infections. Larger, well-designed clinical trials with standardized parameters and extended follow-up are needed to further evaluate its efficacy and optimize treatment protocols for routine clinical application.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503270","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":"Pharmacokinetics of Snake Antivenom Following Intravenous and Intramuscular Administration in Envenomed Large Animal Model.","authors":"Erika Gamulin, Sanja Mateljak Lukačević, Maja Lang Balija, Ana Smajlović, Dražen Vnuk, Jadranka Gulan Harcet, Maja Tomičić, Ana Hećimović, Beata Halassy, Tihana Kurtović","doi":"10.3390/pharmaceutics17020212","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020212","url":null,"abstract":"<p><p><b>Background</b>: The parenteral administration of antivenoms is the mainstay in snakebite envenoming therapy. The standardized protocol does not exist, but it is agreed that the intravenous (<i>i.v.</i>) route is more effective than the others, especially the intramuscular (<i>i.m.</i>) route, based on the monitoring of venom/antivenom pharmacokinetics in the systemic circulation. Recent evidence suggests that the lymphatic system may be crucial in abolishing venom action. <b>Methods:</b> A preclinical study was performed to determine the optimal administration route with emphasis on venom/antivenom interplay in both the blood and lymph of experimentally envenomed sheep. Timed level measurements were used to compare the antivenom effect on the decrement of venom quantities in both relevant body compartments. Hematological and coagulation parameters, as well as proportions of developed anti-antivenom IgGs, were evaluated. <b>Results:</b> The <i>i.m.</i> antivenom resulted in faster and greater lymphatic absorption and complete neutralization of the venom, whereas the <i>i.v.</i> antivenom only slowed its absorption. The total amount of venom reaching the lymph (AUC_0-<i>t</i>) was two times lower after <i>i.m.</i> administration. In the systemic circulation, <i>i.m.</i> antivenom had a lower peak concentration (<i>c</i>_max) and a longer time to reach it (<i>t</i>_max). However, the total venom exposure was three times lower than with <i>i.v.</i> antivenom. Irrespective of the treatment approach, both groups showed improvement in blood disorders with no significant difference in humoral response against equine F(ab')₂ fragments. <b>Conclusions:</b><i>I.m.</i> administration proved to be a viable option for the snakebite management.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503300","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":"Emerging Trends in Snake Venom-Loaded Nanobiosystems for Advanced Medical Applications: A Comprehensive Overview.","authors":"Álisson E F Alves, Anne B C Barros, Lindomara C F Silva, Lucas M M Carvalho, Graziela M A Pereira, Ana F C Uchôa, José M Barbosa-Filho, Marcelo S Silva, Karla P O Luna, Karla S R Soares, Francisco H Xavier-Júnior","doi":"10.3390/pharmaceutics17020204","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020204","url":null,"abstract":"<p><p>Advances in medical nanobiotechnology have notably enhanced the application of snake venom toxins, facilitating the development of new therapies with animal-derived toxins. The vast diversity of snake species and their venom complexities underline the need for ongoing research. This review is dedicated to exploring the integration of snake venom with nanoparticles to enable their use in human therapies aiming to develop treatments. The complex mixture of snake venom not only inflicts significant pathological effects but also offers valuable insights for the creation of innovative therapies, particularly in the realm of nanobiotechnology. Nanoscale encapsulation not only mitigates the inherent toxicity of snake venom but also amplifies their antitumoral, antimicrobial, and immunomodulatory properties. The synergy between venom-derived macromolecules and nanotechnology offers a novel pathway for augmenting the efficacy and safety of conventional antivenom therapies, extending their applicability beyond treating bites to potentially addressing a myriad of health issues. In conclusion, nanotechnology presents a compelling therapeutic frontier that promises to improve current treatment modalities and ameliorate the adverse effects associated with venomous snakebites.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503261","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 Novel LC-MS/MS Method for the Measurement of Elexacaftor, Tezacaftor and Ivacaftor in Plasma, Dried Plasma Spot (DPS) and Whole Blood in Volumetric Absorptive Microsampling (VAMS) Devices.","authors":"Federica Pigliasco, Alessia Cafaro, Sebastiano Barco, Federico Cresta, Rosaria Casciaro, Nicoletta Pedemonte, Francesca Mattioli, Carlo Castellani, Giuliana Cangemi","doi":"10.3390/pharmaceutics17020200","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020200","url":null,"abstract":"<p><p><b>Background:</b> The combination of ivacaftor, tezacaftor and elexacaftor (ETI) is approved for patients with cystic fibrosis (CF) aged two years and older and at least one F508del mutation in the CFTR gene. Variability in ETI treatment response has been repeatedly reported, and its reasons are unclear and understudied. <b>Objectives:</b> We present a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the rapid and simultaneous quantification of ETI in plasma, dried plasma spots (DPS), and whole blood volumetric absorptive microsampling (VAMS). <b>Methods:</b> The method utilizes a rapid extraction protocol with 200 μL methanol after the addition of deuterated internal standards. Chromatographic separation was achieved using a reversed-phase Hypersil Gold aQ column (Thermo Fisher Scientific). The method was validated according to ICH (International Council on Harmonisation) guidelines M10 for bioanalytical method validation, demonstrating linearity in the concentration range 0.020-12.000 µg/mL. It was also proved accurate and reproducible with no matrix effect. This method was applied to anonymized samples from patients undergoing ETI treatment: eight plasma and DPS and five VAMS samples were analyzed. <b>Results:</b> ETI concentrations measured in plasma and DPS were interchangeable, whereas ETI concentrations in VAMS were lower than in plasma, as expected for molecules with high plasma protein binding (99%). A correction factor based on the hematocrit value was used to calculate the equivalent plasma concentration from VAMS concentrations. <b>Conclusions:</b> This method is suitable for pharmacokinetic (PK) studies and could facilitate the centralization of samples to specialized laboratories, supporting multicenter studies.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503264","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":"PLGA-Based Strategies for Intranasal and Pulmonary Applications.","authors":"Hossein Omidian, Renae L Wilson","doi":"10.3390/pharmaceutics17020207","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020207","url":null,"abstract":"<p><p>Poly(D,L-lactide-co-glycolide) (PLGA) has emerged as a cornerstone in the development of advanced drug delivery systems, particularly for intranasal and pulmonary routes. Its biodegradability, biocompatibility, and adaptability make it an ideal platform for addressing challenges associated with conventional therapies. By enabling sustained and controlled drug release, PLGA formulations reduce dosing frequency, improve patient compliance, and enhance therapeutic efficacy. These systems demonstrate versatility, accommodating hydrophilic and hydrophobic drugs, biological molecules, and co-delivery of synergistic agents. Moreover, surface modifications and advanced preparation techniques enhance targeting, bioavailability, and stability, expanding PLGA's applications to treat complex diseases such as tuberculosis, cancer, pulmonary fibrosis, and CNS disorders. This manuscript provides an in-depth review of PLGA's materials, properties, preparation methods, and therapeutic applications, alongside a critical evaluation of challenges and future opportunities in this field.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503311","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":"Sustained Delivery of Liraglutide Using Multivesicular Liposome Based on Mixed Phospholipids.","authors":"Runpeng Zhang, Xinyu Yao, Siqi Gao, Tingting Xu, Da Wang, Luping Sha, Li Yang","doi":"10.3390/pharmaceutics17020203","DOIUrl":"https://doi.org/10.3390/pharmaceutics17020203","url":null,"abstract":"<p><p><b>Background:</b> Although peptides are widely used in the clinical treatment of various diseases due to their strong biological activity, they usually require frequent injections owing to their poor in vivo half-life. Therefore, there is a strong clinical need for sustained peptide formulations. <b>Methods:</b> In this study, liraglutide (Lir) and biocompatible multivesicular liposomes (MVLs) were utilized as the model drug and sustained-release carriers, respectively. The drug release rate of Lir-MVLs was controlled by changing the ratio of SPC and DEPC with different phase transition temperatures (PTT, PTT_SPC = -20 °C, PTT_DEPC = 13 °C). <b>Results:</b> As the SPC ratio increased, Lir-MVLs had more flexible lipid membranes, poorer structural stabilization, and fewer internal vesicles with larger particle sizes, contributing to faster release of Lir. After subcutaneous injection of Lir-MVLs, the blood glucose concentration (BGC) of db/db mice decreased to different levels. When the SPC-DEPC ratio was greater than 85:15, the drug release rate was too fast; the BGC remained below 16 mM for only 2-4 days, while when the drug release rate was too slow, was the case when the SPC-DEPC ratio was less than 50:50, the BGC also remained below 16 mM for only 2-3 days. However, when the SPC-DEPC ratio was 75:25, the BGC could be maintained below 16 mM for 8 days, indicating that the release properties of this ratio best met the pharmacological requirements of Lir. <b>Conclusions:</b> This study investigated the effects of phospholipids with different PTT on the release characteristics of Lir-MVLs, and provided ideas for the design of sustained-release peptide preparations.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503343","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}