Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-05-02DOI: 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":"<p><p>Q fever is a zoonotic infectious disease caused by <i>Coxiella burnetii,</i> 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 <i>C. burnetii</i> 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 <i>in vivo</i>. 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.</p>","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}
{"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":"<p><p>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.</p>","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}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2024-12-11DOI: 10.1080/10717544.2024.2439272
Aleksandra Steć, Monika Targońska, Shishir Jaikishan, Rui Chen, Piotr Mucha, Grzegorz S Czyrski, Jacek Jasiecki, Agata Płoska, Andrea Heinz, Susanne K Wiedmer, Leszek Kalinowski, Krzysztof Waleron, Bartosz Wielgomas, Szymon Dziomba
{"title":"Incorporation of doxorubicin into plant-derived nanovesicles: process monitoring and activity assessment.","authors":"Aleksandra Steć, Monika Targońska, Shishir Jaikishan, Rui Chen, Piotr Mucha, Grzegorz S Czyrski, Jacek Jasiecki, Agata Płoska, Andrea Heinz, Susanne K Wiedmer, Leszek Kalinowski, Krzysztof Waleron, Bartosz Wielgomas, Szymon Dziomba","doi":"10.1080/10717544.2024.2439272","DOIUrl":"10.1080/10717544.2024.2439272","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are an experimental class of drug carriers. Alternative sources of EVs are currently being explored to overcome limitations related to their manufacturing from mesenchymal stem cells. In this work, <i>Citrus limon-</i>derived EVs were tested as carriers for the widely used chemotherapeutic drug - doxorubicin (DOX). Capillary electrophoresis (CE) and nanoplasmonic sensing (NPS) were developed for the quality control of DOX-EV preparations. It was found that the CE method enables simultaneous detection of free and incorporated DOX and allows assessing the stability of the preparations and the drug leakage. NPS, on the other hand, demonstrated that DOX is accumulated in the interfacial region of the carrier. The activity of DOX-loaded EVs was tested on HeLa (cervical cancer cells) and HEK293T (human embryonic kidney cells) cell lines. It was found that DOX incorporation into plant-derived EVs virtually does not affect the drug's cytotoxicity to HeLa cells but significantly decreases DOX activity against HEK293T cell line.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2439272"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11639057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812441","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}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-08-07DOI: 10.1080/10717544.2025.2541660
Megan O Conrad, Molly E Laird, Mary Beth Privitera, Melissa R Lemke, Molly Follette Story
{"title":"Seeking a common human factors language for the development and testing of injection devices.","authors":"Megan O Conrad, Molly E Laird, Mary Beth Privitera, Melissa R Lemke, Molly Follette Story","doi":"10.1080/10717544.2025.2541660","DOIUrl":"10.1080/10717544.2025.2541660","url":null,"abstract":"<p><p>Injection devices include drug-device combination products incorporating a needle for subcutaneous medication delivery. Often utilized by patients and caregivers, it is important for injection device user interface (UI) design to be intuitive to use outside of a traditional healthcare setting. To ensure safety and efficacy, the FDA requires a human factors (HFs) assessment as part of a new drug application (NDA) for new drug products and through the abbreviated new drug application (ANDA) pathway for generic drug approval. Despite the importance of defining injection device features as part of the HFs assessment, no comprehensive list of related definitions has previously been established. This paper compiles such definitions creating a common language for use in HFs assessments. Specifically, injection device classifications and characteristics are defined and then related to UI features and common tasks required for successful devices use. Information presented can be applied during device development and testing creating a common language for engineers, designers, and regulators. The definitions may be especially impactful for the approval of generic injection devices as the ANDA pathway for generic drugs requires a UI comparison of the proposed generic device to that of the existing reference listed drug.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2541660"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793801","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}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-08-04DOI: 10.1080/10717544.2025.2537813
Rohan Medhekar, Laura Clark, Santosh Gautam, Annelore Cortoos
{"title":"Letter to the Editor regarding 'Evaluating nurse preferences for a novel on-body delivery system vs. manual syringes for large-volume subcutaneous drug administration: a survey study'.","authors":"Rohan Medhekar, Laura Clark, Santosh Gautam, Annelore Cortoos","doi":"10.1080/10717544.2025.2537813","DOIUrl":"10.1080/10717544.2025.2537813","url":null,"abstract":"","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2537813"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774888","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}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-06-27DOI: 10.1080/10717544.2025.2522109
Zhuomin Sha, Yongjia Wu, Yi Zheng, Ke Yang, Xinyi Gong, Lu Xuan, Xiang Li, Xuepeng Chen
{"title":"Advances in pH-responsive drug delivery systems for periodontitis treatment.","authors":"Zhuomin Sha, Yongjia Wu, Yi Zheng, Ke Yang, Xinyi Gong, Lu Xuan, Xiang Li, Xuepeng Chen","doi":"10.1080/10717544.2025.2522109","DOIUrl":"10.1080/10717544.2025.2522109","url":null,"abstract":"<p><p>Periodontitis is a prevalent and destructive inflammatory disease that is closely linked to various systemic conditions. In recent years, the local delivery of therapeutic agents via novel biomaterials has emerged as a promising strategy for periodontitis therapy. Notably, the pathological reduction of endogenous power of hydrogen (pH) within periodontal pockets provides a valuable trigger for stimuli-responsive drug delivery. This narrative review aims to summarize advances in endogenous pH-responsive drug delivery systems (DDS) for periodontitis treatment, with a focus on their design mechanisms and therapeutic potential. A comprehensive literature search was conducted in PubMed/Medline, Web of Science, Scopus, and Embase (up to March 2025) using keywords 'pH-responsive', 'drug delivery', and 'periodontitis'. Studies investigating the preparation and <i>in vitro/in vivo</i> therapeutic effects of pH-responsive DDS for periodontitis were included and critically evaluated. pH-responsive materials are capable of undergoing structural transformations and triggering drug release in the pathological acidic microenvironment of periodontitis. The DDS based on these materials can be broadly classified into three categories: nanoparticles, nanofibers, and hydrogels. The protonation and the cleavage of chemical bonds are the primary response mechanisms. Programmed periodontitis recovery is crucial in the design of these DDS. pH-responsive DDS offer a promising strategy for localized periodontal therapy. However, challenges such as clinical translation, biosafety evaluation, and personalized release modulation remain. Future research should focus on multifunctional, programmable platforms to accelerate clinical adoption.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2522109"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505136","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}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-08-21DOI: 10.1080/10717544.2025.2545515
Xin Shen, Xinyu Zhao, Clare F McCoy, Yahya H Dallal Bashi, Peter Boyd, R Karl Malcolm
{"title":"Use of hydrophilic pharmaceutical excipients to modulate release of metal ions from silicone elastomers.","authors":"Xin Shen, Xinyu Zhao, Clare F McCoy, Yahya H Dallal Bashi, Peter Boyd, R Karl Malcolm","doi":"10.1080/10717544.2025.2545515","DOIUrl":"https://doi.org/10.1080/10717544.2025.2545515","url":null,"abstract":"<p><p>Silicone elastomers based on polydimethylsiloxane are biocompatible and non-biodegradable thermosetting polymers used in various drug delivery applications, including subdermal implants, vaginal rings, and intrauterine devices. Without exception, all marketed silicone elastomer drug delivery products provide sustained or controlled release of highly hydrophobic small drug molecules, since drug solubility in the silicone matrix is a prerequisite for molecular diffusion and release. We are interested in developing multipurpose silicone elastomer vaginal rings for local administration of metal ions-such as copper and zinc-for non-hormonal contraception and antimicrobial therapy. However, sustained/controlled release of metal ions from silicone elastomers containing metal nanopowders or metal salts is challenging due to their limited solubility in silicone. In this study, we assess the potential for enhancing the release of copper or zinc ions from silicone elastomer devices by co-formulating copper nanopowder, zinc nanopowder, copper sulfate, or zinc acetate with four common pharmaceutical excipients-gelatin, polyvinylpyrrolidone, sucrose, and hydroxypropyl methylcellulose. The study demonstrates that (i) copper/zinc nanopowders and salts can be successfully incorporated into addition-cure silicone elastomers, (ii) <i>in vitro</i> release of Cu<sup>2+</sup>/Zn<sup>2</sup> ions from silicone elastomers loaded with divalent salts was ∼100 times greater compared to nanopowders; (iii) incorporation of gelatin, polyvinylpyrrolidone, sucrose and hydroxypropyl methylcellulose significantly enhanced the release of Cu<sup>2+</sup>/Zn<sup>2+</sup> ions (up to ∼30-fold), and (iv) enhanced release was due to water absorption into the silicone elastomer devices, causing swelling of the devices to an extent proportional to the excipient loading.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2545515"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946421","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}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-07-11DOI: 10.1080/10717544.2025.2525223
Hong Cheng, Youjie Wang, Yanlong Hong, Fei Wu, Lan Shen, Xiao Lin
{"title":"Characteristics, preparation and applicability in oral delivery systems of cellulose ether-based buccal films.","authors":"Hong Cheng, Youjie Wang, Yanlong Hong, Fei Wu, Lan Shen, Xiao Lin","doi":"10.1080/10717544.2025.2525223","DOIUrl":"10.1080/10717544.2025.2525223","url":null,"abstract":"<p><p>With the rapid development of buccal films (BFs), the demand for film-forming materials and preparation techniques has increased. Cellulose ethers (CEs) exhibit favorable properties, such as effective film formation, mucosal adhesion, and biocompatibility; as such, they are most commonly employed as film-forming materials, essential for BF fabrication. CE-based BFs, classified as orodispersible and buccal mucoadhesive films, can be prepared through solvent casting, inkjet printing, three-dimensional printing, electrospinning, and hot melt extrusion. Hydrophilic CE-based orodispersible films can rapidly dissolve or disintegrate upon contact with saliva to release drugs. High-viscosity or hydrophobic CEs can serve as protective layers for BFs, controlling the unidirectional release of drugs and mitigating the effects of saliva and buccal movements. These mucoadhesive films can firmly adhere to the buccal mucosa for an extended period, prolonging drug release time and enhancing bioavailability. CEs come in various types and grades, exhibiting different rheological and physicomechanical properties, which also provide options for customized design to specific patients. This review provides an overview of CE-based BF technology, analyzes the challenges and development directions of this film, and identifies key areas for scientific research, such as the interactions of bioadhesive materials in buccal mucosal drug delivery. The objectives of this review are to (i) highlight the value of their application in oral drug delivery and (ii) promote the broader adoption of BF-based patient-centric dosing.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2525223"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607772","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":"Transfersomal delivery of <i>Centella asiatica</i> promotes efficient excision wound healing in rats.","authors":"Sarawut Lapmanee, Phichaporn Bunwatcharaphansakun, Waleewan Phongsupa, Katawut Namdee, Khomson Suttisintong, Udom Asawapirom, Uracha Ruktanonchai, Prapimpun Wongchitrat, Sakkarin Bhubhanil, Phornphimon Maitarad, Mattaka Khongkow","doi":"10.1080/10717544.2025.2563649","DOIUrl":"10.1080/10717544.2025.2563649","url":null,"abstract":"<p><p>This study presents the development and evaluation of <i>Centella Asiatica</i> (CA)-loaded transfersomes (CANP) as a novel nanocarrier for transdermal delivery. CANP were prepared using an oil-in-water emulsion method, producing nanoparticles with a size of 135.22 ± 4.80 nm, a polydispersity index of 0.22 ± 0.01, and a zeta potential of -26.13 ± 0.58 mV. Stability tests confirmed consistent physicochemical properties under various storage conditions, with encapsulation efficiencies above 68% for madecassoside and 89% for asiaticoside. <i>Ex vivo</i> permeation studies using porcine skin showed significantly improved skin penetration compared to liposomes and niosomes, attributed to the high deformability index (1.31 ± 0.21 mg/cm<sup>2</sup>). <i>In vitro</i> cytotoxicity assays indicated cell viability above 80% across concentrations. Functionally, CANP reduced nitric oxide production in LPS-stimulated RAW 264.7 cells, demonstrating superior anti-inflammatory effects over native CA. CANP also promoted fibroblast proliferation and collagen production by 91.9% and 213.3% at days 7 and 14, respectively, exceeding vitamin C. Wound healing assays confirmed enhanced fibroblast migration and closure rates similar to fibroblast growth factor. <i>In vivo</i>, CANP hydrogels accelerated healing, with early fibroblast activity and collagen deposition between days 7-14, supporting epithelial regeneration over 21 days. Compared to controls, they more effectively reduced inflammation and increased dermal growth factor expression. These findings support CANP as a promising transdermal nanocarrier with enhanced skin penetration, anti-inflammatory activity, and regenerative potential. Encapsulating CA into transfersomes boosts its therapeutic efficacy, making it a strong candidate for advanced dermal applications.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2563649"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191324","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}
Drug DeliveryPub Date : 2024-12-01Epub Date: 2024-10-20DOI: 10.1080/10717544.2024.2415579
Imke Rudnik-Jansen, Jie Du, Nina Karssemakers-Degen, Anna R Tellegen, Parvesh Wadhwani, Daniele Zuncheddu, Björn P Meij, Jens Thies, Pieter Emans, Fetullah C Öner, George Mihov, Joao Pedro Garcia, Anne S Ulrich, Sibylle Grad, Marianna A Tryfonidou, Hugo van Ingen, Laura B Creemers
{"title":"Drug retention after intradiscal administration.","authors":"Imke Rudnik-Jansen, Jie Du, Nina Karssemakers-Degen, Anna R Tellegen, Parvesh Wadhwani, Daniele Zuncheddu, Björn P Meij, Jens Thies, Pieter Emans, Fetullah C Öner, George Mihov, Joao Pedro Garcia, Anne S Ulrich, Sibylle Grad, Marianna A Tryfonidou, Hugo van Ingen, Laura B Creemers","doi":"10.1080/10717544.2024.2415579","DOIUrl":"10.1080/10717544.2024.2415579","url":null,"abstract":"<p><p>Intradiscal drug delivery is a promising strategy for treating intervertebral disk degeneration (IVDD). Local degenerative processes and intrinsically low fluid exchange are likely to influence drug retention. Understanding their connection will enable the optimization of IVDD therapeutics. Release and retention of an inactive hydrophilic fluorine-19 labeled peptide (<sup>19</sup>F-P) as model for regenerative peptides was studied in a whole IVD culture model by measuring the <sup>19</sup>F-NMR (nuclear magnetic resonance) signal in culture media and IVD tissue extracts. In another set-up, noninvasive near-infrared imaging was used to visualize IR-780, as hydrophobic small molecular drug model, retention upon injection into healthy and degenerative caudal IVDs in a rat model of disk degeneration. Furthermore, IR-780-loaded degradable polyester amide microspheres (PEAM) were injected into healthy and needle pricked degenerative IVDs, subcutaneously, and in knee joints with and without surgically-induced osteoarthritis (OA). Most <sup>19</sup>F-P was released from the IVD after 7 days. IR-780 signal intensity declined over a 14-week period after bolus injection, without a difference between healthy and degenerative disks. IR-780 signal declined faster in the skin and knee joints compared to the IVDs. IR-780 delivery by PEAMs enhanced disk retention beyond 16 weeks. Moreover, in degenerated IVDs the IR-780 signal was higher over time than in healthy IVDs while no difference between OA and healthy joints was noted. We conclude that the clearance of peptides and hydrophobic small molecules from the IVD is relatively fast. These results illustrate that development of controlled release formulations should take into account the target anatomical location and local (patho)biology.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"31 1","pages":"2415579"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460840","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}