Journal of Controlled Release最新文献

{"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}

{"title":"An environment-responsive platform based on acid-resistant metal organic framework for efficient oral insulin delivery.","authors":"Yingnan Zhu, Ruikang Zhang, Wenwen Gao, Fei Li, Mei Yang, Jie Feng, Yalan Ji, Jiahang Si, Xiangrong Wang, Yuze Dong","doi":"10.1016/j.jconrel.2024.11.045","DOIUrl":"https://doi.org/10.1016/j.jconrel.2024.11.045","url":null,"abstract":"<p><p>Oral insulin delivery is considered a revolutionary alternative to daily subcutaneous injections in terms of compliance and convenience. However, significant challenges remain in terms of inactivation in gastrointestinal environment and limited permeation across the intestinal epithelium. Herein, we used acid-resistant metal-organic framework (PCN-222) to load insulin and modified the exterior with sodium dodecyl sulfate (SDS) to achieve efficient oral insulin delivery. The PCN-222 nanocarrier with ordered mesoporous cage structure and suitable pore size achieved a high insulin loading of 75 %. The SDS on the surface of nanocarrier reduces its hydrophilicity while reversibly altering cell morphology and increasing epithelial cell permeability, thereby promoting intestinal epithelial absorption. The constructed particle (I@P@S) was encapsulated in sodium alginate (SA) microspheres to protect it from gastric acid degradation and releases it upon entry into the intestinal tract. Through an uptake pathway dominated by clathrin-mediated endocytosis, the released I@P@S realized efficient intestinal permeability and controlled insulin release under physiological conditions due to the phosphate sensitivity of PCN-222, leading to an in vivo bioavailability of 12.9 %. This work provides a valuable reference for the design of oral insulin delivery systems.</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":"142729022","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 “Golgi-customized Trojan horse nanodiamonds impair GLUT1 plasma membrane localization and inhibit tumor glycolysis [371 (2024) 338–350]”","authors":"Bei Kang ,&nbsp;Haobo Wang ,&nbsp;Huaqing Jing ,&nbsp;Yunsheng Dou ,&nbsp;Sona Krizkova ,&nbsp;Zbynek Heger ,&nbsp;Vojtech Adam ,&nbsp;Nan Li","doi":"10.1016/j.jconrel.2024.11.040","DOIUrl":"10.1016/j.jconrel.2024.11.040","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 339-340"},"PeriodicalIF":10.5,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694208","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":"Therapeutic co-assemblies for synergistic NSCLC treatment through dual topoisomerase I and tubulin inhibitors.","authors":"Hehe Xiong, Chao Du, Jinmin Ye, Heng Zhang, Yatong Qin, Fantian Zeng, Ruirui Song, Changrong Shi, Huifeng Guo, Jiang Chen, Huaxiang Shen, Yanfen Cui, Zijian Zhou","doi":"10.1016/j.jconrel.2024.11.054","DOIUrl":"https://doi.org/10.1016/j.jconrel.2024.11.054","url":null,"abstract":"<p><p>Camptothecin (CPT) and podophyllotoxin (PPT) function as topoisomerase (TOP) I and tubulin inhibitors, respectively, with potent anticancer effects in a variety of cancers. Despite its promise, the clinical applicability of the combination of CPT and PPT faces challenges, including potential side effect and limited therapeutic efficacy. In this study, we designed co-assembly nanomedicines with the different weight (w/w) ratios of amphiphilic Evans blue conjugated CPT prodrug (EB-ss-CPT) and PPT molecules, denoted as ECT Nano. The co-assembly of EB-ss-CPT and PPT without other excipients has nearly 100 % drug loading efficiency and high drug loading content of PPT of up to 74.29 ± 0.90 wt%. Notably, the ECT Nano (1:2) equipped with the ability to inhibit TOP I activity and tubulin polymerization, which provided a highly efficient strategy to improve synergistic efficacy and decrease side toxicity in non-small cell lung cancer mouse model. This work represents a step forward to the development of practical applications for dual TOP I and tubulin inhibitors and especially hopeful to the rational design of combination nanomedicine for therapeutic purposes.</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":"142729099","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":"Enhanced secretion of growth factors from ADSCs using an enzymatic antioxidant hydrogel in inflammatory environments and its therapeutic effect","authors":"Kiyoon Min,&nbsp;Myeongseok Jung,&nbsp;Giyoong Tae","doi":"10.1016/j.jconrel.2024.11.041","DOIUrl":"10.1016/j.jconrel.2024.11.041","url":null,"abstract":"<div><div>A catalytic ROS-scavenging hydrogel (HGel) was developed to enhance the growth factor secretion and the therapeutic efficacy of human adipose-derived stem cells (hADSCs) in inflammatory environments. The HGel is composed of heparin and hyaluronic acid, further functionalized with hemin to endow superoxide dismutase and catalase activities. The functionalization of hemin enables the HGel to effectively scavenge ROS (superoxide and H₂O₂), thereby protecting encapsulated hADSCs from oxidative stress and maintaining their metabolic activities. As a result, the HGel enhanced growth factor secretion of hADSCs in inflammatory conditions compared to non-functionalized, bare heparin/hyaluronic acid hydrogel (Gel). The therapeutic efficacy of the hADSC-encapsulated HGel (C/HGel) was evaluated in a diabetic wound model. The C/HGel significantly accelerated wound closure, reduced ROS levels, mitigated inflammation, and promoted angiogenesis compared to the hADSC-encapsulated Gel (C/Gel) as well as the HGel itself. The HGel has the potential to be utilized as an excellent cell carrier for stem cell therapy in various inflammatory diseases. Overall, this study demonstrated a strategy of enhancing growth factor secretion from stem cells using catalytic antioxidant hydrogels for superior regenerative effects in cell therapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 301-314"},"PeriodicalIF":10.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687206","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":"Active trans-corneal drug delivery with ocular adhesive micelles for efficient glaucoma therapy.","authors":"Qiuyu Wei, Chenchen Zhu, Guiping Yuan, Jiahui Jin, Jing Zhang, Wufa Fan, Ying Piao, Shiqun Shao, Sen Lin, Jiajia Xiang, Youqing Shen","doi":"10.1016/j.jconrel.2024.11.050","DOIUrl":"https://doi.org/10.1016/j.jconrel.2024.11.050","url":null,"abstract":"<p><p>Efficient and noninvasive drug delivery for glaucoma therapy necessitates prolonged retention on the ocular surface and deep penetration into the cornea. However, inherent physiological defenses such as rapid tear clearance and low cornea permeability present significant challenges that hinder the effectiveness of trans-corneal drug delivery. In this study, we demonstrate the potential of zwitterionic micelles composed of poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate)-block-poly(ε-caprolactone) (OPDEA-PCL) amphiphiles as a biocompatible carrier for trans-corneal drug delivery. These micelles exhibit enhanced adhesion to ocular tissues and resistance to tear clearance due to their unique affinity for cell membranes. These characteristics facilitate adsorptive-mediated transcytosis, significantly augmenting trans-corneal transport and intraocular accumulation of the glaucoma medication brinzolamide (BRZ). As a result, OPDEA-PCL/BRZ formulations effectively normalize intraocular pressure in an open-angle glaucoma rat model, surpassing PEGylated and free BRZ formulations. This research underscores the potential utility of OPDEA-PCL micelles as a promising vehicle for noninvasive topical trans-corneal drug delivery in glaucoma therapy.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716352","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":"Enzymatic nanomotors with chemotaxis for product-based cancer therapy","authors":"Haixin Tan ,&nbsp;Ziwei Hu ,&nbsp;Jiajun Miao ,&nbsp;Bin Chen ,&nbsp;Huaan Li ,&nbsp;Junbin Gao ,&nbsp;Yicheng Ye ,&nbsp;Wenxin Xu ,&nbsp;Jiamiao Jiang ,&nbsp;Hanfeng Qin ,&nbsp;Hao Tian ,&nbsp;Fei Peng ,&nbsp;Yingfeng Tu","doi":"10.1016/j.jconrel.2024.11.042","DOIUrl":"10.1016/j.jconrel.2024.11.042","url":null,"abstract":"<div><div>The development of an intelligent nanomotor system holds great promise for enhancing the efficiency and effectiveness of antitumor therapy. Leveraging the overexpressed substances in the tumor microenvironment as propellants and chemotactic factors for enzyme-powered nanomotors represents a versatile and compelling approach. Herein, a plasma amine oxidase (PAO)-based chemotactic nanomotor system has been successfully developed, with the ability to enzymatically produce toxic acrolein and H₂O₂ from the upregulated polyamines (PAs) in the tumor microenvironment for active tumor therapy. Zwitterionic polymeric nanoparticles with superior biocompatibility are synthesized, followed by PAO modification <em>via</em> electrostatic interactions. As expected, the resulting nanomotor system exhibits positive chemotaxis toward PAs concentration gradient. Upon reaching the tumor region, our nanomotors, actuated by the tumor microenvironmental PAs, effectively enhance diffusion and enable deep penetration into the tumor site. This leads to the induction of tumor apoptosis and simultaneous inhibition of tumor invasion and migration by decomposing PAs into toxic products. By smartly utilizing the consumption of these local chemotactic factors and their enzymatic products, our nanomotor system provides a versatile and intelligent platform for active and enhanced tumor therapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 288-300"},"PeriodicalIF":10.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687208","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":"Toward precision medicine: End-to-end design and construction of integrated microneedle-based theranostic systems","authors":"Yiming Qin ,&nbsp;Feiyun Cui ,&nbsp;Yifei Lu ,&nbsp;Peng Yang ,&nbsp;Weiming Gou ,&nbsp;Zixuan Tang ,&nbsp;Shan Lu ,&nbsp;H. Susan Zhou ,&nbsp;Gaoxing Luo ,&nbsp;Xiaoyan Lyu ,&nbsp;Qing Zhang","doi":"10.1016/j.jconrel.2024.11.020","DOIUrl":"10.1016/j.jconrel.2024.11.020","url":null,"abstract":"<div><div>With the growing demand for precision medicine and advancements in microneedle technology, microneedle-based drug delivery systems have evolved into integrated theranostic platforms. However, the development of these systems is currently limited by the absence of clear conclusions and standardized construction strategies. The end-to-end concept offers an innovative approach to theranostic systems by creating a seamless process that integrates target sampling, sensing, analysis, and on-demand drug delivery. This approach optimizes each step based on data from the others, effectively eliminating the traditional separation between drug delivery and disease monitoring. Furthermore, by incorporating artificial intelligence and machine learning, these systems can enhance reliability and efficiency in disease management, paving the way for more personalized and effective healthcare solutions. Based on the concept of end-to-end and recent advancements in theranostic systems, nanomaterials, electronic components, micro-composites, and data science, we propose a modular strategy for constructing integrated microneedle-based theranostic systems by detailing the methods and functions of each critical component, including monitoring, decision-making, and on-demand drug delivery units, though the total number of units might vary depending on the specific application. Notably, decision-making units are emerging trends for fully automatic and seamless systems and featured for integrated microneedle-based theranostic systems, which serve as a bridge of real-time monitoring, on-demand drug delivery, advanced electronic engineering, and data science for personalized disease management and remote medical application. Additionally, we discuss the challenges and prospects of integrated microneedle-based theranostic systems for precision medicine and clinical application.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"377 ","pages":"Pages 354-375"},"PeriodicalIF":10.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692893","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}