Drug Delivery最新文献_第6页

Albumin-based nanoparticles encapsulating SN-38 demonstrate superior antitumor efficacy compared to irinotecan. 与伊立替康相比，包裹SN-38的白蛋白纳米颗粒显示出更好的抗肿瘤功效。

IF 8.1 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-08-17 DOI: 10.1080/10717544.2025.2545519

Guojun Xiong, Shengxi Li, Andreas G Schätzlein, Ijeoma F Uchegbu

{"title":"Albumin-based nanoparticles encapsulating SN-38 demonstrate superior antitumor efficacy compared to irinotecan.","authors":"Guojun Xiong, Shengxi Li, Andreas G Schätzlein, Ijeoma F Uchegbu","doi":"10.1080/10717544.2025.2545519","DOIUrl":"10.1080/10717544.2025.2545519","url":null,"abstract":"Efficient formulation of SN-38 for broad-spectrum chemotherapy remains an unmet medical need. The limited solubility of SN-38 in both aqueous and organic solvents poses a major challenge for formulation development. As a result, the predominant strategy, polymer-SN-38 drug conjugates, often involves complex synthetic procedures and low drug loading (1-5% w/w). Such limitations hinder their large-scale production and clinical translation. In this study, we developed an encapsulation strategy that utilizes the reversible lactone-carboxylate equilibrium of SN-38 to simplify the formulation process and achieve enhanced drug loading. The major issue of SN-38 solubility in organic solvents was effectively addressed by sodium hydroxide (NaOH)-induced conversion of the lactone to the carboxylate form. We have demonstrated that SN-38 carboxylate, once encapsulated within human serum albumin-polylactic acid (HSA-PLA) nanoparticles, retains its reversibility and can be converted back to the active lactone form simply by the addition of hydrochloric acid (HCl). The drug loading capacity of SN-38 in the HSA-PLA nanoparticles was increased to 19% w/w. In vitro cytotoxicity assays confirmed that HSA-PLA (SN-38) nanoparticles exhibited significantly lower IC50 values (0.5-194 nM) across multiple cancer cell lines compared to the clinical standard, irinotecan (CPT-11), indicating superior potency under physiological conditions. In vivo studies in 4T1 and MDA-MB-231 tumor-bearing mice further validated the enhanced therapeutic efficacy of this formulation. Overall, this study presents a promising alternative strategy for SN-38 delivery via encapsulation rather than polymer-drug conjugation, significantly simplifying the formulation process and enhancing the translational potential of SN-38 for broad chemotherapeutic applications.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2545519"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862216","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}

引用次数: 0

Preparation, quality evaluation and preliminary pharmacokinetic-pharmacodynamic studies of synephrine dry powder inhaler. 辛弗林干粉吸入器的制备、质量评价及药动药效学初步研究。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-04-07 DOI: 10.1080/10717544.2025.2486346

Jiming Ke, Shenao Li, Miaomiao Zi, Jing Zhang, Shan Huang, Wenhui Luo, Hailun Han, Jiwen Zhang, Can Peng

{"title":"Preparation, quality evaluation and preliminary pharmacokinetic-pharmacodynamic studies of synephrine dry powder inhaler.","authors":"Jiming Ke, Shenao Li, Miaomiao Zi, Jing Zhang, Shan Huang, Wenhui Luo, Hailun Han, Jiwen Zhang, Can Peng","doi":"10.1080/10717544.2025.2486346","DOIUrl":"10.1080/10717544.2025.2486346","url":null,"abstract":"Acute lung injury (ALI) is a lung disease characterized by pulmonary edema caused by an excessive inflammatory response within the lungs and disruption of the alveolar capillary barrier, with a high morbidity and mortality rate in critically ill patients. Dry powder inhalers (DPI) are an effective way of administering medication to improve efficacy, and inhalation administration not only improves efficacy but also increases the bioavailability of the drug. Synephrine, a natural ingredient derived from the fruit of the citrus plant in the Brassicaceae family, has anti-inflammatory and antioxidant properties. In the present study, we prepared a synephrine dry powder inhaler (SYN-DPI) by anti-solvent precipitation method and evaluated it in vivo and in vitro. The in vitro results show that SYN-DPI has low hygroscopicity and good aerodynamic properties. The in vitro and in vivo efficacy results showed that SYN-DPI not only had low toxicity but also possessed good anti-inflammatory and antioxidant capacity, which could significantly reduce inflammation, oxidative stress, and lung injury. Pharmacokinetic results showed that inhalation administration significantly increased SYN bioavailability. In conclusion, this study provides inhalation administration of synephrine as an inhalable formulation that can be used to improve ALI.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2486346"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802832","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}

引用次数: 0

External stimuli-responsive drug delivery to the posterior segment of the eye. 外部刺激反应性药物递送至眼后段。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-03-24 DOI: 10.1080/10717544.2025.2476140

Shuting Xu, Yaming Zhang, Jia Li, Xinyu Zhang, Weiping Wang

{"title":"External stimuli-responsive drug delivery to the posterior segment of the eye.","authors":"Shuting Xu, Yaming Zhang, Jia Li, Xinyu Zhang, Weiping Wang","doi":"10.1080/10717544.2025.2476140","DOIUrl":"10.1080/10717544.2025.2476140","url":null,"abstract":"Posterior segment eye diseases represent the leading causes of vision impairment and blindness globally. Current therapies still have notable drawbacks, including the need for frequent invasive injections and the associated risks of severe ocular complications. Recently, the utility of external stimuli, such as light, ultrasound, magnetic field, and electric field, has been noted as a promising strategy to enhance drug delivery to the posterior segment of the eye. In this review, we briefly summarize the main physiological barriers against ocular drug delivery, focusing primarily on the recent advancements that utilize external stimuli to improve treatment outcomes for posterior segment eye diseases. The advantages of these external stimuli-responsive drug delivery strategies are discussed, with illustrative examples highlighting improved tissue penetration, enhanced control over drug release, and targeted drug delivery to ocular lesions through minimally invasive routes. Finally, we discuss the challenges and future perspectives in the translational research of external stimuli-responsive drug delivery platforms, aiming to bridge existing gaps toward clinical use.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2476140"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691137","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}

引用次数: 0

Exploring the effects of cannabidiol encapsulation in liposomes on their physicochemical properties and biocompatibility. 探讨大麻二酚包封脂质体对其理化性质和生物相容性的影响。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-02-06 DOI: 10.1080/10717544.2025.2460666

Inga Jurgelane, Karina Egle, Andra Grava, Dana Galkina, Margarita Brante, Maksims Melnichuks, Marite Skrinda-Melne, Girts Salms, Arita Dubnika

{"title":"Exploring the effects of cannabidiol encapsulation in liposomes on their physicochemical properties and biocompatibility.","authors":"Inga Jurgelane, Karina Egle, Andra Grava, Dana Galkina, Margarita Brante, Maksims Melnichuks, Marite Skrinda-Melne, Girts Salms, Arita Dubnika","doi":"10.1080/10717544.2025.2460666","DOIUrl":"10.1080/10717544.2025.2460666","url":null,"abstract":"Cannabidiol (CBD) is recognized for its therapeutic properties in various conditions. However, CBD's limited water solubility and sensitivity to environmental stresses hinder its efficacy and bioavailability. Encapsulation in drug delivery systems, particularly liposomes, offers a promising solution. This study aims to prepare CBD-containing liposomes using commercially used lipids distearoyl phosphatidylcholine (DSPC) and dipalmitoyl phosphatidylcholine (DPPC), and 1,2 distearoyl-sn-glycero-3 phosphoethanolamine-N-[carbonyl-amino(polyethylene glycol)-4300] (ammonium salt) (DSPE-PEG) and to perform in vitro studies - cell viability and CBD release. Liposomes were synthesized using thin-film hydration method, and characterized by Fourier-transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS), and scanning transmission electron microscopy (STEM). DLS analysis revealed that CBD incorporation reduced liposome size by 23-53%, depending on the liposomes. Encapsulation efficiency followed the order: DPPC CBD (63%) < DSPC CBD (74%) < DSPC DPPC CBD (81%) < DSPC DSPE-PEG CBD (87%). CBD release profiles indicated that DPPC CBD liposomes released the highest CBD amount initially, while DSPC DSPE-PEG CBD exhibited sustained release, achieving 79% release over 504 h. In vitro cell viability tests showed that blank liposomes were non-cytotoxic. However, CBD-loaded liposomes significantly reduced cell viability for defined type of CBD containing liposomes. The inclusion of DSPE-PEG improved encapsulation efficiency and liposome stability, making DSPC DSPE-PEG CBD liposomes more suitable for long-term CBD release. Compared to other studies, encapsulation of CBD in liposomes enhances its bioavailability, allowing lower concentrations of CBD to be directly delivered to cells, resulting in observable changes in cell viability.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2460666"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364061","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}

引用次数: 0

Advances in vaccine adjuvant development and future perspectives. 疫苗佐剂开发进展及未来展望。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-06-19 DOI: 10.1080/10717544.2025.2517137

Genada Sinani, Sevda Şenel

{"title":"Advances in vaccine adjuvant development and future perspectives.","authors":"Genada Sinani, Sevda Şenel","doi":"10.1080/10717544.2025.2517137","DOIUrl":"10.1080/10717544.2025.2517137","url":null,"abstract":"Use of highly purified antigens to improve vaccine safety has led to reduced immunogenicity and efficacy, resulting in the need for adjuvants to increase and/or modulate the immunogenicity of the vaccine. Despite the need for potent and safe vaccine adjuvants, currently, there are still very few adjuvants in licensed human vaccines. Advances in immunology and molecular biology, especially in the last decade, have allowed researchers to understand better how the adjuvants work and enhance immune responses. While aluminum salts are still the most widely used adjuvants, research has shifted toward the rational design of adjuvant systems containing immunostimulatory molecules. Application of systems biology, which is based on high-throughput technologies using mathematical and computational modeling, has provided a deeper understanding of the biological events elicited by vaccination as well as the influence of other factors such as sex, age, microbiota, genetics and metabolism on the immune response. By this means, it became possible to tailor potential vaccine adjuvants more precisely for a successful vaccine with enhanced efficacy, safety and protection. In this review, after describing the mechanism of action of the adjuvants, current adjuvants in licensed vaccines, as well as those under clinical development will be mentioned in detail. Finally, new approaches in vaccine adjuvant development using systems biology and artificial intelligence will be reviewed, and future directions in vaccine research in regard to efficacy, safety and quality aspects will be discussed.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2517137"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324814","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}

引用次数: 0

Electroporation induced changes in extracellular vesicle profile. 电穿孔引起细胞外囊泡轮廓的改变。

IF 8.1 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-09-22 DOI: 10.1080/10717544.2025.2562224

M Singh, G Mazaheri-Tehrani, I Martin-Fabiani, O G Davies

{"title":"Electroporation induced changes in extracellular vesicle profile.","authors":"M Singh, G Mazaheri-Tehrani, I Martin-Fabiani, O G Davies","doi":"10.1080/10717544.2025.2562224","DOIUrl":"10.1080/10717544.2025.2562224","url":null,"abstract":"Extracellular vesicles (EVs) are promising drug delivery systems (DDSs). Electroporation is widely applied in the loading of therapeutic payloads but has not been optimized for EV loading. Understanding the potential effects of electroporation on EV profile and integrity is important if they are to be applied therapeutically. In the present study, EVs were isolated and subjected to electroporation at different voltages (500-1000 mV), pulse numbers (1-3), and pulse widths (10-30 ms). Particle concentration, size distribution, polydispersity index (PDI), zeta potential (ZP), and protein concentration were analyzed and western blotting was performed to evaluate possible variations in EV surface markers. Suspension in electroporation buffer (EB) significantly reduced EV concentration, increased particle size, and reduced the ZP. Native EV profile could not be recovered following washing. Electroporation parameters (EPs) applied had variable effects on in EV profile, with reductions in surface protein concentration and a more neutral ZP observed. In conclusion, we identified that the electroporation protocol had a considerable impact on basic EV properties, which could impact their application as DDS. Further optimization of EBs and protocols is required to retain native EV profile following loading.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2562224"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112270","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}

引用次数: 0

Biomimetic peptide conjugates as emerging strategies for controlled release from protein-based materials. 仿生肽偶联物作为蛋白质基材料控释的新兴策略。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-01-09 DOI: 10.1080/10717544.2025.2449703

Juthatip Manissorn, Jaturong Promsuk, Kittikhun Wangkanont, Peerapat Thongnuek

{"title":"Biomimetic peptide conjugates as emerging strategies for controlled release from protein-based materials.","authors":"Juthatip Manissorn, Jaturong Promsuk, Kittikhun Wangkanont, Peerapat Thongnuek","doi":"10.1080/10717544.2025.2449703","DOIUrl":"10.1080/10717544.2025.2449703","url":null,"abstract":"Biopolymers, such as collagens, elastin, silk fibroin, spider silk, fibrin, keratin, and resilin have gained significant interest for their potential biomedical applications due to their biocompatibility, biodegradability, and mechanical properties. This review focuses on the design and integration of biomimetic peptides into these biopolymer platforms to control the release of bioactive molecules, thereby enhancing their functionality for drug delivery, tissue engineering, and regenerative medicine. Elastin-like polypeptides (ELPs) and silk fibroin repeats, for example, demonstrate how engineered peptides can mimic natural protein domains to modulate material properties and drug release profiles. Recombinant spider silk proteins, fibrin-binding peptides, collagen-mimetic peptides, and keratin-derived structures similarly illustrate the ability to engineer precise interactions and to design controlled release systems. Additionally, the use of resilin-like peptides showcases the potential for creating highly elastic and resilient biomaterials. This review highlights current achievements and future perspectives in the field, emphasizing the potential of biomimetic peptides to transform biopolymer-based biomedical applications.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2449703"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946591","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}

引用次数: 0

In vivo antitumor activity of PHT-427 inhibitor-loaded polymeric nanoparticles in head and neck squamous cell carcinoma. 负载PHT-427抑制剂的聚合纳米颗粒在头颈部鳞状细胞癌中的体内抗肿瘤活性。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-01-09 DOI: 10.1080/10717544.2024.2449376

Joaquín Yanes-Díaz, Raquel Palao-Suay, Francisca Inmaculada Camacho-Castañeda, Juan Riestra-Ayora, María Rosa Aguilar, Ricardo Sanz-Fernández, Carolina Sánchez-Rodríguez

{"title":"In vivo antitumor activity of PHT-427 inhibitor-loaded polymeric nanoparticles in head and neck squamous cell carcinoma.","authors":"Joaquín Yanes-Díaz, Raquel Palao-Suay, Francisca Inmaculada Camacho-Castañeda, Juan Riestra-Ayora, María Rosa Aguilar, Ricardo Sanz-Fernández, Carolina Sánchez-Rodríguez","doi":"10.1080/10717544.2024.2449376","DOIUrl":"10.1080/10717544.2024.2449376","url":null,"abstract":"Recent studies on head and neck squamous cell carcinoma (HNSCC) tumorigenesis have revealed several dysregulated molecular pathways. The phosphatidylinositol-3-kinase (PI3K) signaling pathway is frequently activated in HNSCC, making it an attractive target for therapies. PHT-427 is a dual inhibitor of PI3K and the mammalian target of AKT/PDK1. This study evaluates the anticancer efficacy of the inhibitor PHT-427 loaded into polymeric nanoparticles (NP) based on α-TOS (NP-427) administered by intratumoral injection into a hypopharyngeal squamous cell carcinoma (FaDu cells) heterotopic xenograft mouse model. The nanocarrier system, based on block copolymers of N-vinylpyrrolidone (VP) and a methacrylic derivative of α-TOS (MTOS), was synthesized, and PHT-427 was loaded into the delivery system. First, we evaluated the effect of NP-427 on tumor growth by measuring tumor volume, mouse weight, survival, and the development of tumor ulceration and necrosis. In addition, we measured PI3KCA/AKT/PDK1 gene expression, PI3KCA/AKT/PDK1 protein levels, Epidermal Growth Factor Receptor (EGFR), and angiogenesis in the tumor tissue. PHT-427 encapsulation increased drug efficacy and safety, as demonstrated by decreased tumor volume, reduced PI3K/AKT/PDK1 pathway expression, and improved antitumor activity and necrosis induction in the mouse xenograft model. EGFR and angiogenesis marker (Factor VIII) expression were significantly lower in the NP-427 group compared to other experimental groups. Administration of encapsulated PHT-427 at the tumor sites proves promising for HNSCC therapy.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2449376"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946592","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}

引用次数: 0

Development of a single-dose Q fever vaccine with an injectable nanoparticle-loaded hydrogel: effect of sustained co-delivery of antigen and adjuvant. 可注射纳米颗粒负载水凝胶的单剂量Q热疫苗的研制：抗原和佐剂持续共同递送的效果。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-05-02 DOI: 10.1080/10717544.2025.2476144

Lu Wang, Aaron Ramirez, Jiin Felgner, Enya Li, Jenny E Hernandez-Davies, Anthony E Gregory, Philip L Felgner, Ali Mohraz, D Huw Davies, Szu-Wen Wang

{"title":"Development of a single-dose Q fever vaccine with an injectable nanoparticle-loaded hydrogel: effect of sustained co-delivery of antigen and adjuvant.","authors":"Lu Wang, Aaron Ramirez, Jiin Felgner, Enya Li, Jenny E Hernandez-Davies, Anthony E Gregory, Philip L Felgner, Ali Mohraz, D Huw Davies, Szu-Wen Wang","doi":"10.1080/10717544.2025.2476144","DOIUrl":"https://doi.org/10.1080/10717544.2025.2476144","url":null,"abstract":"Q fever is a zoonotic infectious disease caused by Coxiella burnetii, and there is currently no FDA-approved vaccine for human use. The whole-cell inactivated vaccine Q-VAX, which is only licensed in Australia, has a risk of causing severe adverse reactions, making subunit vaccines a good alternative. However, most subunit antigens are weak immunogens and require two or more immunizations to elicit an adequate level of immunity. We hypothesized that by combining a nanoparticle to co-deliver both a protein antigen and an adjuvant, together with a hydrogel depot for sustained-release kinetics, a single-administration of a nanoparticle-loaded hydrogel vaccine could elicit a strong and durable immune response. We synthesized and characterized a protein nanoparticle (CBU-CpG-E2) that co-delivered the immunodominant protein antigen CBU1910 (CBU) from C. burnetii and the adjuvant CpG1826 (CpG). For sustained release, we examined different mixtures of PLGA-PEG-PLGA (PPP) polymers and identified a PPP solution that was injectable at room temperature, formed a hydrogel at physiological temperature, and continuously released protein for 8 weeks in vivo. Single-dose vaccine formulations were administered to mice, and IgG, IgG1, and IgG2c levels were determined over time. The vaccine combining both the CBU-CpG-E2 nanoparticles and the PPP hydrogel elicited a stronger and more durable humoral immune response than the soluble bolus nanoparticle vaccines (without hydrogel) and the free antigen and free adjuvant-loaded hydrogel vaccines (without nanoparticles), and it yielded a balanced IgG2c/IgG1 response. This study demonstrates the potential advantages of using this modular PPP hydrogel/nanoparticle system to elicit improved immune responses against infectious pathogens.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2476144"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994984","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}

引用次数: 0

Synergistic effect of pH-sensitive PEGylated RG3-chitosan prodrug nanoparticles encapsulated celastrol on pancreatic cancer. ph敏感聚乙二醇化rg3 -壳聚糖前药纳米颗粒包封雷公酚对胰腺癌的协同作用。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-02-16 DOI: 10.1080/10717544.2025.2464189

Zheng Zhang, Jiaxing Wang, Xiaofang Li, Lingzhou Zhao, Junwei Zhao, Mengjiao Su, Xiangxiang Wu, Huahui Zeng

{"title":"Synergistic effect of pH-sensitive PEGylated RG3-chitosan prodrug nanoparticles encapsulated celastrol on pancreatic cancer.","authors":"Zheng Zhang, Jiaxing Wang, Xiaofang Li, Lingzhou Zhao, Junwei Zhao, Mengjiao Su, Xiangxiang Wu, Huahui Zeng","doi":"10.1080/10717544.2025.2464189","DOIUrl":"10.1080/10717544.2025.2464189","url":null,"abstract":"Celastrol (Cel) is a potential anticancer therapeutic candidate, but its limited practical applicability is due to its low solubility, poor tumor selectivity, and cytotoxicity. Clinically, ginsenoside Rg3 (RG3) is typically combined with chemotherapy to enhance antitumor effects and reduce side effects. Herein, we developed novel pH-sensitive prodrug nanoparticles (NPs) containing RG3 and Cel for the synergistic treatment of pancreatic cancer (PC). Amphiphilic prodrug, a PEGylated chitosan oligosaccharide coupled with RG3 via Schiff base bond, was self-assembled with hydrophobic Cel into NPs with drug loadings of 2.12% (Cel) and 1.63% (RG3). NPs exhibited a suitable particle size of 124.01 nm, zeta potential of -39.89 mV and good physical stability. In addition, NPs also showed a controlled drug release when the Schiff base bonds were hydrolyzed in the acidic environment. In Pan02 tumor-bearing mice, NPs exhibited a high accumulation in tumor tissues and prolonged blood circulation time. Furthermore, NPs could more effectively inhibit tumor growth and reduce systemic toxicity, compared with the free Cel, RG3, prodrug, and Cel + RG3. The results indicated that the NPs could provide a safe and promising nanoplatform for PC therapy.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2464189"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432677","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}

引用次数: 0