Journal of Controlled Release最新文献

{"title":"Dentin tubules as a long-term sustained release carrier to accelerate bone repair by loading FTY720","authors":"Jiaman Xie ,&nbsp;Haohui Huang ,&nbsp;Shijing Xu ,&nbsp;Keyi Zhou ,&nbsp;Xiaofeng Chen ,&nbsp;Jingxian Fang ,&nbsp;Fujian Zhao","doi":"10.1016/j.jconrel.2024.11.051","DOIUrl":"10.1016/j.jconrel.2024.11.051","url":null,"abstract":"<div><div>The controlled release of drugs remains a huge challenge in the field of tissue engineering. Current research focuses on the construction of drug carriers by using various advanced technologies. However, the pore-like structure that exists within our human body is ignored. Herein, a dental particle loaded with FTY720 by using dentin tubules (Dent-FTY720) was successfully prepared, which could achieve long-term sustained release of drugs. Meanwhile, Dent-FTY720 significantly promoted bone defect repair because of the similarity in composition to bone including hydroxyapatite and collagen. Furthermore, the loaded drugs exhibited both anti-immune and anti-inflammatory properties. This research introduces a novel concept in drug loading, highlighting the potential of dentin tubules as a drug delivery system.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 446-457"},"PeriodicalIF":10.5,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710265","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":"Nuplon: New synthetic polymers fully degradable in water.","authors":"John Garner, Kinam Park","doi":"10.1016/j.jconrel.2024.11.067","DOIUrl":"https://doi.org/10.1016/j.jconrel.2024.11.067","url":null,"abstract":"<p><p>New crosslinked polyesters, which are fully degradable in the presence of water over several months in the environment, were synthesized by direct polyesterification of multi-hydroxylic alcohols (e.g., pentaerythritol or glycerol), multi-carboxylic acids (e.g., citric acid), and hydroxy acid compounds (e.g., lactic acid). The reaction produced a crosslinked matrix with mechanical properties of solid and useful degradability in the environment. This reaction can be performed with moderate heat (100-200 °C) and without requiring the aid of additional catalysts, inert gas, or vacuum. The crosslinked matrix can be thermoplastic or thermoset, depending on the extent of crosslinking, which is controlled by reaction time and temperature. The polyesters formed with various ratios of the monomers degrade in water in 12 h at 95 °C, 3 days at 70 °C, and about 3 months at 30 °C. These environmentally degradable alkyl polyesters include a range of mechanical strengths and elasticity, making them suitable for various applications. These environmentally degradable, synthetic polymers can replace current non-degradable polymers in various applications. These new polymers are named \"Nuplons\".</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754932","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":"Corrigendum to “Gold core@CeO2 halfshell Janus nanocomposites catalyze targeted sulfate radical for periodontitis therapy” [Journal of Controlled Release 370 (2024) 600–613]","authors":"Sijia Li ,&nbsp;Qihang Ding ,&nbsp;Lingling Zhang ,&nbsp;Fangyu Shi ,&nbsp;Chengyu Liu ,&nbsp;Tingxuan Li ,&nbsp;Yujia Shi ,&nbsp;Manlin Qi ,&nbsp;Lin Wang ,&nbsp;Biao Dong ,&nbsp;Shuyan Song ,&nbsp;Jiao Sun ,&nbsp;Jong Seung Kim ,&nbsp;Chunyan Li","doi":"10.1016/j.jconrel.2024.11.049","DOIUrl":"10.1016/j.jconrel.2024.11.049","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 442-445"},"PeriodicalIF":10.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718608","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":"Interaction design in mRNA delivery systems","authors":"Mengyao Yu ,&nbsp;Lixin Lin ,&nbsp;Dezhong Zhou ,&nbsp;Shuai Liu","doi":"10.1016/j.jconrel.2024.11.038","DOIUrl":"10.1016/j.jconrel.2024.11.038","url":null,"abstract":"<div><div>Following the coronavirus disease 2019 (COVID-19) pandemic, mRNA technology has made significant breakthroughs, emerging as a potential universal platform for combating various diseases. To address the challenges associated with mRNA delivery, such as instability and limited delivery efficacy, continuous advancements in genetic engineering and nanotechnology have led to the exploration and refinement of various mRNA structural modifications and delivery platforms. These achievements have significantly broadened the clinical applications of mRNA therapies. Despite the progress, the understanding of the interactions in mRNA delivery systems remains limited. These interactions are complex and multi-dimensional, occurring between mRNA and vehicles as well as delivery materials and helper ingredients. Resultantly, stability of the mRNA delivery systems and their delivery efficiency can be both significantly affected. This review outlines the current state of mRNA delivery strategies and summarizes the interactions in mRNA delivery systems. The interactions include the electrostatic interactions, hydrophobic interactions, hydrogen bonding, π-π stacking, coordination interactions, and so on. This interaction understanding provides guideline for future design of next-generation mRNA delivery systems, thereby offering new perspectives and strategies for developing diverse mRNA therapeutics.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 413-426"},"PeriodicalIF":10.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695542","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":"Amniotic fluid stem cell extracellular vesicles promote lung development via TGF-beta modulation in a fetal rat model of oligohydramnios","authors":"Fabian Doktor ,&nbsp;Rebeca Lopes Figueira ,&nbsp;Victoria Fortuna ,&nbsp;George Biouss ,&nbsp;Kaya Stasiewicz ,&nbsp;Mikal Obed ,&nbsp;Kasra Khalaj ,&nbsp;Lina Antounians ,&nbsp;Augusto Zani","doi":"10.1016/j.jconrel.2024.11.043","DOIUrl":"10.1016/j.jconrel.2024.11.043","url":null,"abstract":"<div><div>Oligohydramnios (decreased amniotic fluid volume for gestational age) is a severe condition associated with high morbidity and mortality mainly due to fetal pulmonary hypoplasia. Currently, there are limited treatment options to promote fetal lung development. Administration of stem cells and their derivates have shown promising regenerative properties for several fetal and neonatal diseases related to arrested lung development. Herein, we first characterized pulmonary hypoplasia secondary to oligohydramnios in a surgical rat model. Experimental induction of oligohydramnios led to impaired lung growth, branching morphogenesis (fewer airspaces with decreased <em>Fgf10</em>, <em>Nrp1</em>, <em>Ctnnb1</em> expression), proximal/distal progenitor cell patterning (decreased Sox2 and Sox9 expression), and TGF-β signaling. We then tested antenatal administration of extracellular vesicles derived from amniotic fluid stem cells (AFSC-EVs). In oligohydramnios lungs, AFSC-EV administration improved lung branching morphogenesis and airway progenitor cell patterning at least in part through the release of miR-93-5p. Our experiments suggest that AFSC-EV miR-93-5p blocked SMAD 7, resulting in upregulation of pSMAD2/3 and restoration of TGF-β signaling. Conversely, oligohydramnios lungs treated with antagomir 93-5p transfected AFSC-EVs had decreased branching morphogenesis and TGF-β signaling. This is the first study reporting that antenatal administration of stem cell derivatives could be a potential therapy to rescue lung development in fetuses with oligohydramnios.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 427-441"},"PeriodicalIF":10.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692887","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":"Dual-phase nanoscissors disrupt vasculature-breast cancer stem cell crosstalk for breast cancer treatment.","authors":"Yao Qi, Shuai Lv, Changheng Xie, Shi Du, Jing Yao","doi":"10.1016/j.jconrel.2024.11.058","DOIUrl":"https://doi.org/10.1016/j.jconrel.2024.11.058","url":null,"abstract":"<p><p>Clinical treatment effects of breast cancer are heavily frustrated by the malignant crosstalk between tumor vasculature and breast cancer stem cells (BCSCs). This study introduces a two-phase therapeutic strategy targeting the interplay between tumor vasculature and BCSCs to overcome this challenge. Here, we designed an FLG/ZnPc nanoscissor, which combines mild photodynamic therapy (PDT) to generate reactive oxygen species (ROS) with vascular normalization therapy (VNT) to break the crosstalk between tumor vessels and BCSCs. In the first phase, our approach breaks the vascular niche that supports BCSCs by restoring tumor vascular function and promoting ROS-induced BCSCs differentiation into less malignant forms, enhancing treatment sensitivity. The second phase employs high-impact photothermal therapy (PTT) to ablate tumor masses. This integrated \"mild PDT-PTT\" approach aims to reduce tumor growth and metastasis, offering a comprehensive strategy for effective breast cancer management.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739604","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":"White paper: Understanding, informing and defining the regulatory science of microneedle-based dosage forms that are applied to the skin.","authors":"Maria Dul, Mohammed Alali, Mahmoud Ameri, Matthew Douglas Burke, Benjamin Paul Creelman, Lisa Dick, Ryan F Donnelly, Michael N Eakins, Collrane Frivold, Angus Harry Forster, Philippe-Alexandre Gilbert, Stefan Henke, Sebastien Henry, Desmond Hunt, Hayley Lewis, Jessica Joyce Mistilis, Jung-Hwan Park, Mark R Prausnitz, David Kenneth Robinson, Carmen Amelia Rodriguez Hernandez, Juyeop Shin, Tycho Joseph Speaker, Caroline Strasinger, Kevin M G Taylor, Darin Zehrung, James C Birchall, Courtney Jarrahian, Sion A Coulman","doi":"10.1016/j.jconrel.2024.11.056","DOIUrl":"https://doi.org/10.1016/j.jconrel.2024.11.056","url":null,"abstract":"<p><p>The COVID-19 pandemic has accelerated pre-clinical and clinical development of microneedle-based drug delivery technology. However the regulatory science of this emerging dosage form is immature and explicit regulatory guidance is limited. A group of international stakeholders has formed to identify and address key issues for the regulatory science of future products that combine a microneedle device and active pharmaceutical ingredient (in solid or semi-solid state) in a single entity that is designed for application to the skin. Guided by the principles of Quality by Design (QbD) and informed by consultation with wider stakeholders, this 'White Paper' describes fundamental elements of the work in an effort to harmonise understanding, stimulate discussion and guide innovation. The paper discusses classification of the dosage form (combination / medicinal product), the regulatory nomenclature that is likely to be adopted and the technical vocabulary that best describes its form and function. More than twenty potential critical quality attributes (CQAs) are identified for the dosage form, and a prioritisation exercise identifies those CQAs that are most pertinent to the dosage form and that will likely require bespoke test methods (delivered dose, puncture performance) or major adaptions to established compendial test methods (dissolution). Hopefully the work will provide a platform for the development of dosage form specific guidance (from regulatory authorities and/or international pharmacopoeias), that expedites clinical translation of safe and effective microneedle-based products.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739622","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":"Subconjunctival injection of microcrystalline prodrug of dexamethasone for long-acting anti-inflammation after phacoemulsification surgery.","authors":"Xueyan Zhou, Zunkai Xu, Yanliang Dong, Maoyu Cai, Zhixia Chen, Jingqing Mu, Bo Yuan, Xia Hua, Xiaoyong Yuan, Shutao Guo","doi":"10.1016/j.jconrel.2024.11.046","DOIUrl":"10.1016/j.jconrel.2024.11.046","url":null,"abstract":"<p><p>Long-acting injectable formulations of dexamethasone with minimal invasiveness are highly desired to manage chronic ocular inflammatory conditions. Here, we applied microcrystals (MCs) of a hydrophobic acetone-based ketal-linked prodrug of dexamethasone (SKD) to treat postoperative ocular inflammation. We compared the efficacy and safety of SKD MCs through subconjunctival (SC) injection with that of Maxidex (a topical suspension of dexamethasone MCs) through SC injection and eye drops in the phacoemulsification combined with intraocular lens implantation (Phaco-IOL) rabbit model. In Phaco-IOL rabbit eyes, a single SC injection of SKD MCs (0.4 mg dexamethasone equiv.) showed anti-inflammatory effects comparable to Maxidex eye drops and completely alleviated the inflammation within 28 days, while an SC injection of Maxidex at the same dose only provided anti-inflammatory effects for 7 days. The study on the dose-dependent anti-inflammatory effects of SKD MCs showed no significant difference in anti-inflammatory effects for the high dosage (0.8 mg dexamethasone equiv.) and the low dosage (0.4 mg dexamethasone equiv.) in 28 days. Nevertheless, systematic drug distribution of SKD MCs and Maxidex in normal rabbits after SC injection demonstrates that the drug concentration in conjunctiva was higher for the high dosage and that a considerable amount of prodrug and dexamethasone could still be detected in the cornea and iris-ciliary body at least 84 days for SKD MCs at high dosage. Furthermore, no persistent elevated intraocular pressure and abnormality in retinal structure and thickness were observed, confirming the excellent safety of long-acting SKD MCs post-SC injection. Our findings provide valuable insights into using prodrug-based MCs for treating ocular postoperative inflammation, and the detailed drug distribution analysis would promote the clinical translation of these MCs in ocular diseases.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"399-412"},"PeriodicalIF":10.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687209","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":"Formulation development of dual-compartment topical inserts combining Tenofovir Alafenamide and Elvitegravir for flexible on-demand HIV prevention.","authors":"Vivek Agrahari, M Melissa Peet, Neelima Chandra, Prakash Ramalingam, Pardeep K Gupta, Sriramakamal Jonnalagadda, Onkar N Singh, Timothy J McCormick, Gustavo F Doncel, Meredith R Clark","doi":"10.1016/j.jconrel.2024.11.062","DOIUrl":"https://doi.org/10.1016/j.jconrel.2024.11.062","url":null,"abstract":"<p><p>Pre-exposure prophylaxis (PrEP) has emerged as a prominent approach for the prevention of HIV infections. While the latest advances have resulted in effective oral and injectable product options, there are still gaps in on-demand, event-driven, topical products for HIV prevention that are safe and effective. Here we describe the formulation development of a dual-compartment topical insert containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) that may be administered when needed, vaginally or rectally, pre- or post-coitus, for flexible HIV prophylaxis. Specifically, we describe the lab-scale formulation development, preclinical mucosal safety and pharmacokinetics (PK) testing in rabbits, long-term stability, and scale-up clinical manufacturing of the lead TAF/EVG (20 mg/16 mg) inserts, which are currently in clinical stages of development. As designed, the inserts are small, discreet and portable, offering a number of promising attributes, such as simple and robust direct-compression manufacturing, fast initial disintegration/dissolution, and suitable mechanical strengths showing low hardness (<8 kg), friability (<1 %), and moisture content (<1 %). The inserts initiated disintegration quickly (~ ≤ 15 min) providing full in vitro release (>90 %) of TAF and EVG within 60 min of dissolution. The lead insert was selected from formulation prototypes that met the evaluation criteria for manufacturability and characterization, together with a dose-ranging PK study in non-human primates. Successful technology transfer for clinical development of the lead TAF/EVG (20 mg/16 mg) insert was confirmed under cGMP conditions. Based on the 12 months (lab-scale) and 24 months (clinical batch) stability data, the TAF/EVG inserts are projected to have a long shelf life of over 2 years, if stored at or below 30 °C/65 % RH. Overall, these newly designed topical inserts have formulation properties that enable stable storage and fast release of the antiretroviral payload from a small, portable and discreet dosage form. They are safe and effective when applied vaginally or rectally, before or after coitus, providing the basis for a new method of flexible on-demand HIV prevention for cisgender and transgender women and men. The TAF/EVG inserts are currently the most clinically advanced on-demand topical product, as attested by their completed and ongoing clinical trials.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729094","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":"Channel-assembling tumor microenvironment on-chip for evaluating anticancer drug efficacy","authors":"Jaehun Lee ,&nbsp;Youngwon Kim ,&nbsp;Hyo-Il Jung ,&nbsp;Jiseok Lim ,&nbsp;Bong Seop Kwak","doi":"10.1016/j.jconrel.2024.11.030","DOIUrl":"10.1016/j.jconrel.2024.11.030","url":null,"abstract":"<div><div>Organ-on-a-chip is an advanced system for evaluating drug response in diseases. It simulates the <em>in vivo</em> tumor microenvironment, aiding in the understanding of drug mechanisms and tumor responses. It mimics the structure of the tumor microenvironment and the dynamic conditions within the body. As a result, it holds the potential for applications in precision and personalized medicine. However, there are still limitations in sequential development processes and complex structures, resulting in time-consuming molecular interference during system development. In this study, we developed a channel-assembling tumor microenvironment-on-chip (CATOC) system to overcome these limitations. CATOC was easily segmented into blood vessels and a tumor microenvironment-on-chip, which can be independently developed. The tumor microenvironment-on-chip consists of two independent channels for evaluating drug responses in different types of tumor microenvironments. Each fully developed system was physically interconnected to create a CATOC. Interconnected CATOC was used to validate chemical and targeted anticancer drug responses in different subtypes of the breast tumor microenvironment. We also emphasized the significance of on-chip experiments by observing the drug response of tumor spheroids on CATOC and scaffold-free platforms.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 376-384"},"PeriodicalIF":10.5,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681953","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}