{"title":"Prolonged, staged, and self-regulated methotrexate release coupled with ROS scavenging in an injectable hydrogel for rheumatoid arthritis therapy","authors":"","doi":"10.1016/j.jconrel.2024.08.046","DOIUrl":"10.1016/j.jconrel.2024.08.046","url":null,"abstract":"<div><p>Rheumatoid arthritis (RA) remains a formidable healthcare challenge due to its chronic nature and potential for irreversible joint damage. Methotrexate (MTX) is a cornerstone treatment for RA but carries significant risks of adverse effects with repeated administration, necessitating the exploration of alternative delivery methods. Injectable hydrogels loaded with MTX for intra-articular injection present a promising solution, allowing sustained drug release directly into affected joints. However, current hydrogel systems often lack extended therapeutic periods and the ability to self-regulate drug release according to disease state. Furthermore, RA is associated with excessive production of reactive oxygen species (ROS), which exacerbates inflammation and joint damage. Herein, we developed an advanced injectable hydrogel (MPDANPs/MTX HA-PEG gel) based on “bio-orthogonal chemistry”, combining hyaluronic acid and polyethylene glycol (PEG) matrices <em>co</em>-loaded with mesoporous polydopamine nanoparticles (MPDANPs) and MTX. MPDANPs/MTX HA-PEG gel achieved prolonged, staged, and self-regulated MTX release, coupled with ROS scavenging capabilities for enhanced therapeutic efficacy. Due to its optimized MTX release behavior and significant ROS scavenging function, MPDANPs/MTX HA-PEG gel exhibited potent anti-inflammatory effects in collagen-induced arthritis (CIA) rats following a single intra-articular injection. Our findings highlight the potential of MPDANPs/MTX HA-PEG gel as a highly effective treatment strategy for RA, offering a promising avenue for improving patient outcomes.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the optimal chain length of modification module in disulfide bond bridged paclitaxel prodrug nanoassemblies for breast tumor treatment","authors":"","doi":"10.1016/j.jconrel.2024.08.052","DOIUrl":"10.1016/j.jconrel.2024.08.052","url":null,"abstract":"<div><p>In the prodrug-based self-assembled nanoassemblies, prodrugs usually consist of drug modules, response modules, and modification modules. Modification modules play a critical role in regulating the nano-assembly ability of the prodrugs. Herein, we carried out a “fatty alcoholization” strategy and chose various lengths of aliphatic alcohol chains (AC) as modification modules to construct disulfide bond bridged paclitaxel (PTX) prodrug nanoassemblies. The PTX-AC prodrugs would self-assemble into nanoassemblies (PTX-AC PNs) with higher drug loading, stability, and tumor selectivity than commercial preparations. After comprehensive exploration, we found the chain length (AC<sub>12</sub>, AC<sub>16</sub>, AC<sub>20</sub>, AC<sub>24</sub>) of modification modules affected the assembly of PTX-AC PNs, further leading to disparate in vivo fate and antitumor efficacy. With the increase of the chain length of the modification modules (from AC<sub>12</sub> to AC<sub>20</sub>), the assembly ability of the nanoassemblies was improved, attributed to the appropriate enhancement of hydrophobic force. When the chain length was further increased to AC<sub>24</sub>, the excessive hydrophobic force will lead to the aggregation of prodrugs and weaken the assembly ability. Therefore, PTX-AC<sub>20</sub> PNs with proper chain length may solve the paradox of efficacy and tolerance in 4 T1 breast tumor owing to their optimal nano-assembly stability and modest redox-sensitivity. In short, this work highlighted the importance of screening optimal modification modules in developing prodrug nanoassemblies.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Liver-targeting chimeras as a potential modality for the treatment of liver diseases","authors":"","doi":"10.1016/j.jconrel.2024.08.044","DOIUrl":"10.1016/j.jconrel.2024.08.044","url":null,"abstract":"<div><p>Liver diseases pose significant challenges to global public health. In the realm of drug discovery and development, overcoming ‘on-target off-tissue’ effects remains a substantial barrier for various diseases. In this study, we have pioneered a Liver-Targeting Chimera (LIVTAC) approach using a proteolysis-targeting chimera (PROTAC) molecule coupled to the liver-specific asialoglycoprotein receptor (ASGPR) through an innovative linker attachment strategy for the precise induction of target protein degradation within the liver. As a proof-of-concept study, we designed XZ1606, a mammalian bromodomain and extra-terminal domain (BET)-targeting LIVTAC agent, which not only demonstrated enduring tumor suppression (over 2 months) in combination with sorafenib but also an improved safety profile, notably ameliorating the incidence of thrombocytopenia, a common and severe on-target dose-limiting toxic effect associated with conventional BET inhibitors. These encouraging results highlight the potential of LIVTAC as a versatile platform for addressing a broad spectrum of liver diseases.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeted delivery of activatable 131I-radiopharmaceutical for sustained radiotherapy with improved pharmacokinetics","authors":"","doi":"10.1016/j.jconrel.2024.07.005","DOIUrl":"10.1016/j.jconrel.2024.07.005","url":null,"abstract":"<div><p><span><span>Targeted radionuclide therapy (TRT) is an effective treatment for tumors. Self-condensation strategies can enhance the retention of radionuclides in tumors and enhance the anti-tumor effect. Considering </span>legumain is overexpressed in multiple types of human cancers, a </span><sup>131</sup><span>I-labeled radiopharmaceutical (</span><strong>[</strong><sup><strong>131</strong></sup><strong>I]MAAN</strong>) based on the self-condensation reaction between 2-cyanobenzothiazole (CBT) and cysteine (Cys) was developed by us recently for treating legumain-overexpressed tumors. However, liver enrichment limits its application. In this study, a new radiopharmaceutical <strong>[</strong><sup><strong>131</strong></sup><strong>I]IM(HE)</strong><sub><strong>3</strong></sub><strong>AAN</strong> was designed and synthesized by introducing a hydrophilic peptide sequence His-Glu-His-Glu-His-Glu ((HE)<sub>3</sub>) into <strong>[</strong><sup><strong>131</strong></sup><strong>I]MAAN</strong><span> to optimize the pharmacokinetics. Upon activation by legumain under a reducing environment, hydrophilic </span><strong>[</strong><sup><strong>131</strong></sup><strong>I]IM(HE)</strong><sub><strong>3</strong></sub><strong>AAN</strong> could react with its precursor to form heterologous dimer <strong>[</strong><sup><strong>131</strong></sup><strong>I]H-Dimer</strong> that is highly hydrophobic. Cerenkov imaging revealed that <strong>[</strong><sup><strong>131</strong></sup><strong>I]IM(HE)</strong><sub><strong>3</strong></sub><strong>AAN</strong> displayed superior tumor selectivity and longer tumor retention time as compared with <strong>[</strong><sup><strong>131</strong></sup><strong>I]MAAN</strong>, with a significant reduction in the liver uptake. After an 18-day treatment with <strong>[</strong><sup><strong>131</strong></sup><strong>I]IM(HE)</strong><sub><strong>3</strong></sub><strong>AAN</strong><span>, the tumor proliferation was obviously inhibited, while no obvious injury was observed in the normal organs. These findings suggest that </span><strong>[</strong><sup><strong>131</strong></sup><strong>I]IM(HE)</strong><sub><strong>3</strong></sub><strong>AAN</strong> could serve as a promising drug candidate for treating legumain-overexpressed tumors.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Drugs need to be formulated with scale-up in mind","authors":"","doi":"10.1016/j.jconrel.2024.07.016","DOIUrl":"10.1016/j.jconrel.2024.07.016","url":null,"abstract":"<div><p>Formulation scale-up remains a major hurdle in drug development in part because preliminary formulation research efforts rarely consider the challenges of scaling up production for commercialization. This Perspective outlines considerations around scalability that can be incorporated into formulation design work in order to increase the chances of successful translation. Both technical (unit operations, excipient selection, scaling principles) and non-technical (funding, publications, and personnel) considerations are discussed, with a focus on lab-scale work by academic researchers.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168365924004474/pdfft?md5=210332156889d394156ef0e6dd1d706d&pid=1-s2.0-S0168365924004474-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Content list including Graphcal Abstracts","authors":"","doi":"10.1016/S0168-3659(24)00570-4","DOIUrl":"10.1016/S0168-3659(24)00570-4","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168365924005704/pdfft?md5=ea3800b80ed6666424500f6ef761c8a1&pid=1-s2.0-S0168365924005704-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142150248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to “Cascade-targeting polymeric particles eliminate intracellular C. neoformans in fungal infection therapy” [Journal of Controlled Release 373 (2024) 399–409]","authors":"","doi":"10.1016/j.jconrel.2024.08.007","DOIUrl":"10.1016/j.jconrel.2024.08.007","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168365924005467/pdfft?md5=49b34c5469afa955e46f7e032c3c55e0&pid=1-s2.0-S0168365924005467-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Outside Back Cover","authors":"","doi":"10.1016/S0168-3659(24)00572-8","DOIUrl":"10.1016/S0168-3659(24)00572-8","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168365924005728/pdfft?md5=58c7ec92352afe17b327075cc1b70e38&pid=1-s2.0-S0168365924005728-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142150247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Forty years Journal of Controlled Release: ‘Quality is not an act, it is a habit’","authors":"","doi":"10.1016/j.jconrel.2024.08.004","DOIUrl":"10.1016/j.jconrel.2024.08.004","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biocompatible polymer-based micro/nanorobots for theranostic translational applications","authors":"","doi":"10.1016/j.jconrel.2024.08.040","DOIUrl":"10.1016/j.jconrel.2024.08.040","url":null,"abstract":"<div><p>Recently, micro/nanorobots (MNRs) with self-propulsion have emerged as a promising smart platform for diagnostic, therapeutic and theranostic applications. Especially, polymer-based MNRs have attracted huge attention due to their inherent biocompatibility and versatility, making them actively explored for various medical applications. As the translation of MNRs from laboratory to clinical settings is imperative, the use of appropriate polymers for MNRs is a key strategy, which can prompt the advancement of MNRs to the next phase. In this review, we describe the multifunctional versatile polymers in MNRs, and their biodegradability, motion control, cargo loading and release, adhesion, and other characteristics. After that, we review the theranostic applications of polymer-based MNRs to bioimaging, biosensing, drug delivery, and tissue engineering. Furthermore, we address the challenges that must be overcome to facilitate the translational development of polymeric MNRs with future perspectives. This review would provide valuable insights into the state-of-the-art technologies associated with polymeric MNRs and contribute to their progression for further clinical development.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142097813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}