Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-03-24DOI: 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":"<p><p>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.</p>","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}
{"title":"Harnessing nanofibers for targeted delivery of phytoconstituents in age-related macular degeneration.","authors":"Ulia Andrades, Sahil Gaikar, Khushali Nathani, Sujata Sawarkar, Abdelwahab Omri","doi":"10.1080/10717544.2025.2489491","DOIUrl":"10.1080/10717544.2025.2489491","url":null,"abstract":"<p><p>Age-related macular degeneration is a degenerative eye condition that affects the macula and results in central vision loss. Phytoconstituents show great promise in the treatment of AMD. AMD therapy can benefit from the advantages of phytoconstituents loaded nanofibers. There are opportunities to improve the effectiveness of phytoconstituents in the treatment of age-related macular degeneration (AMD) through the use of nanofiber-based delivery methods. These novel platforms encapsulate and distribute plant-derived bioactives by making use of the special qualities of nanofibers. These qualities include their high surface area-to-volume ratio, variable porosity, and biocompatibility. Exploring the use of nanofiber-based delivery methods to provide phytoconstituents in AMD treatment is a great choice for enhancing patient adherence, safety, and efficacy in managing this condition. This article explores the potential of nanofiber-based delivery methods to revolutionize AMD treatment, providing an innovative and effective approach to treat this condition.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2489491"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794964","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: 2025-02-06DOI: 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":"<p><p>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 <i>in vitro</i> 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. <i>In vitro</i> 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.</p>","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}
{"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":"<p><p>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 <i>Brassicaceae family</i>, 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 <i>in vivo</i> and <i>in vitro</i>. The <i>in vitro</i> results show that SYN-DPI has low hygroscopicity and good aerodynamic properties. The <i>in vitro</i> and <i>in vivo</i> 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.</p>","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}
{"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":"<p><p>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.</p>","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}
Drug DeliveryPub Date : 2025-12-01Epub Date: 2025-01-09DOI: 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":"<p><p>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.</p>","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}
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 : 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}