International Journal of Pharmaceutics最新文献

{"title":"In-situ hyaluronic acid-tyramine hydrogels prolong the release of extracellular vesicles and enhance stability","authors":"Yingchang Ma,&nbsp;Ines Colic,&nbsp;Maha Muwaffak,&nbsp;Ahad A. Rahim,&nbsp;Steve Brocchini,&nbsp;Gareth R. Williams","doi":"10.1016/j.ijpharm.2025.125650","DOIUrl":"10.1016/j.ijpharm.2025.125650","url":null,"abstract":"<div><div>Hydrogels can provide a hydrated environment to encapsulate extracellular vesicles (EVs) while offering promising solutions to some of the challenges that limit their therapeutic potential, e.g. rapid clearance and propensity for enzymatic degradation and aggregation. This study explores the use of a hyaluronic acid-tyramine (HA-TA) hydrogel to prolong the delivery and enhance the stability of EVs. EVs were obtained from lentiviral-transduced HEK293T cells expressing luciferase and eGFP to enable easy quantification. Two encapsulation strategies were evaluated: (1) pre-loading, where EVs were mixed with HA-TA (2.58 % degree of substitution) precursor solution and subsequently crosslinked with 2 U/mL horseradish peroxidase (HRP) and 0.05 mM H₂O₂; and (2) post-loading, where EVs were soaked into pre-formed dehydrated hydrogels. Both methods improved EV stability over 7 days at 37 °C compared to free EVs. The pre-loading approach was ultimately selected due to its ability to give rapid <em>in situ</em> gelation within one minute. Controlled <em>in vitro</em> release of EVs from the pre-loaded hydrogels was observed to extend beyond 7 days, as determined by CD9 ELISA. The released EVs maintained their bioactivity, as evidenced by effective internalisation into ARPE-19 and H9c2 cell lines, with performance comparable to fresh EVs. The EV release profile could be varied by modifying the hydrogel concentration. These findings underscore the potential of HA-TA hydrogels for localised, sustained, EV delivery with preserved functionality.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125650"},"PeriodicalIF":5.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918376","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":"Biomimetic surfactants for tunable interfacial properties in drug delivery, biomedical coatings and tissue engineering","authors":"Karuppiah Nagaraj ,&nbsp;Ganesh Kumar Anbazhagan ,&nbsp;Rekha Shree Govindasamy ,&nbsp;Vennmathi Muthu ,&nbsp;Suraj Rajkumar ,&nbsp;Samritha Senthilnathan ,&nbsp;Sriyasasvi Muddana ,&nbsp;Rithvika Reddy Esanakula ,&nbsp;Dheeksha Sivakumar ,&nbsp;Chiranjeevulu Deepa Harini Sri ,&nbsp;Mohammed fayaz lathief Mujibur Rahman ,&nbsp;Rithvik Ravi ,&nbsp;Madhoomitha Senthil Murugan ,&nbsp;Gurupriya Rajendren","doi":"10.1016/j.ijpharm.2025.125658","DOIUrl":"10.1016/j.ijpharm.2025.125658","url":null,"abstract":"<div><div>Biomimetic surfactants have emerged as a powerful class of interfacial agents designed to mimic biological amphiphiles, offering tunable physicochemical properties for drug delivery and biomedical coatings. This review explores the fundamental characteristics of biomimetic surfactants, comparing their advantages over synthetic and natural counterparts in modulating interfacial behaviors such as surface tension reduction, wettability control, and self-assembly into micellar structures. The role of surfactants in stabilizing lipid-based nanocarriers, polymer-surfactant hybrids, and bioinspired drug delivery systems is examined, highlighting their ability to enhance solubility, bioavailability, and targeted therapeutic delivery. Additionally, integrating surfactants into biomedical coatings has demonstrated significant potential in antifouling, antibacterial, and hemocompatible applications, crucial for implant safety, wound healing, and tissue engineering. Computational modeling, including molecular dynamics simulations, alongside experimental characterization techniques such as FTIR, DLS, TEM, and AFM, are pivotal in optimizing surfactant design for enhanced performance. Despite their promising applications, challenges remain in achieving stability, scalability, and regulatory approval for clinical translation. Future advancements in multifunctional and stimuli-responsive surfactants could revolutionize biomedical engineering, enabling next-generation drug delivery platforms and bioactive coatings. This review provides a comprehensive insight into the current progress, challenges, and future perspectives of biomimetic surfactants, paving the way for innovative and clinically viable solutions in biomedical applications.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125658"},"PeriodicalIF":5.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895156","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":"Glucosamine sulphate endorsed ibuprofen nanocrystals burdened polymeric gel demonstrated multidimensional anti-inflammatory and cartilage protective potential in experimental knee osteoarthritis: In vitro and in vivo studies","authors":"Keerthana Radapaka ,&nbsp;Atul Mourya ,&nbsp;Hoshiyar Singh ,&nbsp;Soham Loharkar ,&nbsp;Ankush Bansode ,&nbsp;Santosh Kumar Guru ,&nbsp;Nandkumar Doijad ,&nbsp;Srinivas Nanduri ,&nbsp;Jitender Madan","doi":"10.1016/j.ijpharm.2025.125660","DOIUrl":"10.1016/j.ijpharm.2025.125660","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a chronic degenerative musculoskeletal condition associated with progressive loss of hyaline cartilage, subchondral bone remodelling, and inflammation. Despite ongoing research, no United States Food and Drug administration (USFDA) approved drugs for OA are available. The current investigation explores the potential of glucosamine sulphate endorsed ibuprofen nanocrystals loaded polymeric gel (IBU-GS-NCs gel) for its anti-inflammatory and disease-modifying capabilities in the osteoarthritic rat model. IBU-GS-NCs were engineered by using the anti-solvent precipitation method that later exhibited particle size 34.57 ± 0.79 nm, zeta (ζ) potential −2.81 ± 0.6 mV, and drug content 7.05 ± 0.19 %. On the other hand, IBU-GS-NCs gel demonstrated 0.507 ± 0.029 % drug loading with spreadability and viscosity close to marketed diclofenac emulgel. Next, the amount of IBU infused through the rat skin in <em>ex vivo</em> permeation study from IBU-GS-NCs gel and IBU gel was calculated to be 479.59 ± 6.28 µg/cm² and 255.91 ± 4.44 µg/cm², respectively after 24 h with 1.87-fold increment. Steady-state flux and permeability coefficient for IBU-GS-NCs gel through rat skin were 31.70 ± 0.11 µg/cm²h and 63.41 ± 0.23×10^-3 cm/h, respectively. In contrast to the positive control, the representative radiograph for IBU-GS-NCs gel-treated osteoarthritic rats indicated regeneration of articular cartilage with the absence of osteophytes. Histological evaluation of IBU-GS-NCs gel illustrated marked recovery in articulate cartilage thickness as well as glycosaminoglycan (GAG) level. Western blot analysis for synovial tissue of positive control displayed a 9.01, 2.66, 2.51 and 5.75-fold increase in COX-2, TNF-α, and IL-1β, Col2a1 respectively as compared to normal control. In contrast, IBU-GS-NCs gel-treated rats demonstrated 6.28, 4.06, 2.81 and 5.54-fold reduction in COX-2, TNF-α, IL-1β, and Col2a1 respectively compared to positive control. These findings advocate for improved anti-inflammatory and cartilage protective potential of IBU-GS-NCs gel. In conclusion, IBU-GS-NCs gel may be a potential candidate for translating into a clinically viable product to offer effective treatment for knee OA.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125660"},"PeriodicalIF":5.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890969","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":"A novel orodispersible film load with dual-coated sustained-release microparticles for pediatric drug delivery","authors":"Qianmeng Huang ,&nbsp;Peng Yan ,&nbsp;Youshan Li ,&nbsp;Jinsong Ding","doi":"10.1016/j.ijpharm.2025.125654","DOIUrl":"10.1016/j.ijpharm.2025.125654","url":null,"abstract":"<div><div>Orodispersible films (ODFs), easy to administer, flexible in dosage, and free of choking and aspiration risks, have drawn widespread attention as pediatric formulations. However, it is a great challenge to endow ODFs with sustained release due to their fast disintegration. Herein, we designed a novel orodispersible film load with dual-coated sustained-release microparticles (SRMPs) for children using topiramate as a model drug. SRMPs with a particle size of 98.32 ± 0.22 µm, fabricated with a pellet core, a drug layer, and a coating layer, were prepared by two microparticle coating steps. The sustained-release orodispersible films (SRODFs) with uniform distribution of SRMPs and favorable disintegration time showed good formability, mechanical properties, and palatability. The factors affecting drug release of the SRMPs and the SRODFs were further explored. More importantly, pharmacokinetics study in human demonstrated that, although the SRODFs had a longer mean retention time, they were bioequivalence compared with the commercially available extended-release products (Qudexy® XR). A strong in vivo-in vitro correlation of the SRODFs was established. Notably, the SRODFs can be loaded with other drugs other than topiramate, offering a promising formulation option for pediatric patients with different diseases.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125654"},"PeriodicalIF":5.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890974","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":"Ellagic acid-loaded chitosan nanoparticles as an approach for mitigating oxidative stress and liver damage in Poloxamer-407-induced hyperlipidemia in mice: Development and optimization through 3 level full factorial design","authors":"Lamiaa Sobhy,&nbsp;Mahmoud Mostafa,&nbsp;Zeinab Fathalla,&nbsp;Amal K. Hussein","doi":"10.1016/j.ijpharm.2025.125659","DOIUrl":"10.1016/j.ijpharm.2025.125659","url":null,"abstract":"<div><div>The primary cause of atherosclerosis and cardiovascular disorders is hyperlipidemia. Ellagic Acid (EA) is a naturally occurring polyphenol found in fruits and nuts. This medication has garnered attention due to its possible therapeutic benefits, encompassing the treatment of hyperlipidemia. In this study, ellagic acid was incorporated into a nanocarrier system using chitosan, a biodegradable polymer, via an ionotropic gelation technique, aiming to enhance its solubility and bioavailability. The effects of ellagic acid-loaded chitosan nanoparticles (EA-CS-NPs) were evaluated in a hyperlipidemic mouse model induced by poloxamer 407 (PL-407). Administration of a single intraperitoneal dose of 300 mg/kg body weight of PL-407 resulted in the induction of hyperlipidemia. The mice were grouped into five groups: Control, PL-407, EA-free drug, blank CS-NPs, and EA-CS-NPs. Serum analysis included the measurement of liver function biomarkers, lipid profiles, and liver antioxidant capacity. Additionally, a histopathological evaluation of liver tissue was performed. This study showed that PL-407 treatment increased hepatic oxidative stress and serum lipid biomarkers, with significant liver tissue changes in hyperlipidemic mice. EA-CS-NPs exerted the most protective effects, improving hepatic antioxidant capacity, serum lipid profile, and hepatic histological changes, highlighting their potential as a therapeutic approach for hyperlipidemia.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125659"},"PeriodicalIF":5.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887959","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":"Harnessing nano-delivery systems to un-cover the challenges for cervical cancer therapy","authors":"Xinyu Wang ,&nbsp;Qi Li ,&nbsp;Jianxin Liu ,&nbsp;Chunbao Xie ,&nbsp;Liang Zou ,&nbsp;Yi Shi ,&nbsp;Lingxi Jiang ,&nbsp;Xianyan Qin","doi":"10.1016/j.ijpharm.2025.125657","DOIUrl":"10.1016/j.ijpharm.2025.125657","url":null,"abstract":"<div><div>Cervical cancer (CC) remains a prevalent malignancy among women, with current therapeutic strategies facing significant challenges in curbing its rising incidence. Nano-delivery systems have emerged as a promising approach to hinder CC progression. This review provides a comprehensive examination of CC pathogenesis and its physiological characteristics while focusing on applying various nano-delivery systems in CC therapy. Specifically, it highlights the potential of both internal (e.g., pH, reactive oxygen species, glutathione) and external (e.g., Photo, magnetism, sound waves, microwaves, electricity) stimuli-responsive nano-delivery platforms to enhance therapeutic efficacy. The challenges of nano-delivery systems in CC therapy, encompassing in vivo stability, biosafety, distribution, and metabolic processes, are addressed, along with potential remedies. Additionally, the review underscores recent preclinical advances in nano-delivery systems for CC therapy. By thoroughly exploring nanomaterial applications, this review provides valuable perspectives for advancing CC treatment and stimulating future research and innovation in this domain.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125657"},"PeriodicalIF":5.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898382","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":"Corrigendum to “Development of nanovehicles for co-delivery of colistin and ArnT inhibitors” [Int. J. Pharm 675 (2025)125515]","authors":"Valentina Pastore ,&nbsp;Jessica Frison ,&nbsp;Cristiano Pesce ,&nbsp;Mariya Ryzhuk ,&nbsp;Mariangela Garofalo ,&nbsp;Martina Cristoferi ,&nbsp;Silvia Cammarone ,&nbsp;Giorgia Fabrizio ,&nbsp;Maria Carmela Bonaccorsi Di Patti ,&nbsp;Deborah Quaglio ,&nbsp;Francesca Ghirga ,&nbsp;Francesco Imperi ,&nbsp;Mattia Mori ,&nbsp;Paolo Caliceti ,&nbsp;Bruno Botta ,&nbsp;Fiorentina Ascenzioni ,&nbsp;Stefano Salmaso","doi":"10.1016/j.ijpharm.2025.125583","DOIUrl":"10.1016/j.ijpharm.2025.125583","url":null,"abstract":"","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125583"},"PeriodicalIF":5.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878535","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":"Elucidating mixing process effects on pulmonary delivery efficiency of dry powder inhalers: A dual-dimensional macroscopic and microscopic perspective","authors":"Xiao Yue ,&nbsp;Junhui Liang ,&nbsp;Yue Zhou ,&nbsp;Ziyu Zhao ,&nbsp;Guanlin Wang ,&nbsp;Yingtong Cui ,&nbsp;Wenhao Wang ,&nbsp;Yinjia Luo ,&nbsp;Chuanbin Wu ,&nbsp;Ying Huang ,&nbsp;Xuejuan Zhang","doi":"10.1016/j.ijpharm.2025.125652","DOIUrl":"10.1016/j.ijpharm.2025.125652","url":null,"abstract":"<div><div>Dry powder inhalers (DPIs) have been widely recommended in lung diseases on account of direct pulmonary delivery, desired drug stability, and satisfactory patient compliance. More than 90% of DPIs products consist of micronized drugs mixed with larger carrier particles for required dose delivery uniformity and desired pulmonary delivery efficiency. In formulation development, researchers often focus on the influence of mixing process on the macroscopic quantitative results of pulmonary drug delivery efficiency. However, the critical influence and underlying modulatory mechanisms of mixing parameters remain poorly understood, posing formidable challenges to the optimization of DPI formulations. In the present study, an internationally recognized cascade impactor method was employed to investigate the effects of mixing parameters on the ultimate pulmonary drug delivery efficiency from a macroscopic perspective. Subsequently, Confocal Microscopic Raman Spectroscopy (CMRS) was applied to innovatively investigate the material distribution and adhesive status of the mixed DPI particles. Meanwhile, the self-constructed Modular Process Analysis Platform (MPAP) was employed the detached behavior during pulmonary delivery, allowing us to explore the influence mechanisms from a microscopic perspective. Ultimately, correlations were established between the mixing parameters and the drug adhesive status, pulmonary drug delivery process and efficiency. This study was expected to provide novelty pioneering paradigms and dual-dimensional perspective for the direction development and optimization of DPIs.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125652"},"PeriodicalIF":5.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887956","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":"Targeting ovarian cancer: The promise of liposome-based therapies","authors":"Jagriti Gupta ,&nbsp;Afeefa Khan ,&nbsp;Shruti Gupta ,&nbsp;Ramasubbamma Ramaiah ,&nbsp;Umme Hani ,&nbsp;Garima Gupta ,&nbsp;Prashant Kesharwani","doi":"10.1016/j.ijpharm.2025.125647","DOIUrl":"10.1016/j.ijpharm.2025.125647","url":null,"abstract":"<div><div>A major cause of mortality among gynecological cancers, ovarian cancer is frequently unresponsive to standard therapies because to systemic toxicity and medication resistance. The contribution of liposomal drug delivery systems, specifically pegylated liposomal doxorubicin (PLD), to the advancement of ovarian cancer treatment is examined in this review. Liposomes, spherical lipid vesicles consisting of bilayer phospholipids, enable better drug delivery by preserving encapsulated pharmaceuticals and enabling tailored administration to tumor areas. In comparison to traditional doxorubicin, PLD has a better pharmacokinetic profile and less cardiotoxicity, according to the analysis, which examines several trials showing its effectiveness in treating both platinum-sensitive and platinum-resistant ovarian cancer. Furthermore, studies on liposomal versions of other medications, such as paclitaxel and cisplatin, demonstrate encouraging effects in terms of overcoming drug resistance and enhancing therapeutic outcomes. Recent advancements in tailored liposomal delivery systems that include components such tumor-specific peptides and folate receptors show improved tumor selectivity and fewer adverse effects. The study also looks at new combination treatments that use liposomal formulations with immunotherapeutic and new targeted medicines. Although liposomal drug delivery methods have great potential for treating ovarian cancer, further study is required to maximize their effectiveness, reduce side effects, and get beyond resistance mechanisms. These developments in liposomal technology are a major step toward turning ovarian cancer from a deadly illness into a chronic condition that can be managed, possibly increasing patient survival and quality of life.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125647"},"PeriodicalIF":5.3,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895157","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":"A biomimetic manganese-phycocyanin nanodrug-carrying system and its sonodynamic-immunological anti-tumor therapy","authors":"Chenyao Qian,&nbsp;Huan Wang,&nbsp;Jinyue Bi,&nbsp;Xiaodan Zheng,&nbsp;Rujia Li,&nbsp;Huan Luo,&nbsp;Xueyong Qi,&nbsp;Song Shen,&nbsp;Jin Cao","doi":"10.1016/j.ijpharm.2025.125626","DOIUrl":"10.1016/j.ijpharm.2025.125626","url":null,"abstract":"<div><div>Cutaneous melanoma is characterized by malignant proliferation, high aggressiveness, high metastasis, rapid recurrence, and low survival rate; therefore, research on its treatment is vital. In this study, a novel nano system combining sonodynamics and immunotherapy for cutaneous melanoma treatment was designed and developed. Based on the use of phycocyanin for the biomineralization of manganese ions, smart and multifunctional manganese phycocyanin nanoparticles encapsulating the immune adjuvant levamisole (LMS) with melanoma B16-OVA cell membranes wrapped around its outer layer (Mn-PCNP-LMS@CM) were designed and prepared. The experimental results showed that Mn-PCNP-LMS@CM efficiently targeted cutaneous melanomas. Under ultrasonic excitation, it catalyzed oxygen production from hydrogen peroxide in the tumor environment, reduced high glutathione levels in tumor tissues, and significantly enhanced (reactive oxygen species) ROS generation, thus improving the outcome of sonodynamic therapy. In contrast, sonodynamic therapy induced immunogenic death of tumor cells, together with the loaded immune adjuvant levamisole, which promoted the maturation of dendritic cells (DCs), modulated the immunosuppressive microenvironment, enhanced the immunotherapeutic effect, and stimulated the function of long-term immune memory to prevent tumor growth and recurrence. This study is expected to provide new ideas for developing novel anti-tumor nano systems and achieving anti-tumor synergistic therapy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"677 ","pages":"Article 125626"},"PeriodicalIF":5.3,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887958","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}