Journal of Controlled Release最新文献

{"title":"Targeted NAD+ repletion via biomimetic nanoparticle enables simultaneous management of intimal hyperplasia and accelerated re-endothelialization: A proof-of-concept study toward next-generation of endothelium-protective, anti-restenotic therapy","authors":"Li Yin ,&nbsp;Yao Tong ,&nbsp;Ruosen Xie ,&nbsp;Zhanpeng Zhang ,&nbsp;Zain Husain Islam ,&nbsp;Kaijie Zhang ,&nbsp;Jacobus Burger ,&nbsp;Nicholas Hoyt ,&nbsp;Eric William Kent ,&nbsp;William Aaron Marcum ,&nbsp;Campbell Johnston ,&nbsp;Rohan Kanchetty ,&nbsp;Zoe Tetz ,&nbsp;Sophia Stanisic ,&nbsp;Yitao Huang ,&nbsp;Lian-Wang Guo ,&nbsp;Shaoqin Gong ,&nbsp;Bowen Wang","doi":"10.1016/j.jconrel.2024.10.045","DOIUrl":"10.1016/j.jconrel.2024.10.045","url":null,"abstract":"<div><div>Endovascular interventions often fail due to restenosis, primarily caused by smooth muscle cell (SMC) proliferation, leading to intimal hyperplasia (IH). Current strategies to prevent restenosis are far from perfect and impose significant collateral damage on the fragile endothelial cell (EC), causing profound thrombotic risks. Nicotinamide adenine dinucleotide (NAD⁺) is a co-enzyme and signaling substrate implicated in redox and metabolic homeostasis, with a pleiotropic role in protecting against cardiovascular diseases. However, a functional link between NAD⁺ repletion and the delicate duo of IH and EC regeneration has yet to be established. NAD⁺ repletion has been historically challenging due to its poor cellular uptake and low bioavailability. We have recently invented the first nanocarrier that enables direct intracellular delivery of NAD⁺ in vivo. Combining the merits of this prototypic NAD⁺-loaded calcium phosphate (CaP) nanoparticle (NP) and biomimetic surface functionalization, we created a biomimetic P-NAD⁺-NP with platelet membrane coating, which enabled an injectable modality that targets IH with excellent biocompatibility. Using human cell primary culture, we demonstrated the benefits of NP-assisted NAD⁺ repletion in selectively inhibiting the excessive proliferation of aortic SMC, while differentially protecting aortic EC from apoptosis. Moreover, in a rat balloon angioplasty model, a single-dose treatment with intravenously injected P-NAD⁺-NP immediately post angioplasty not only mitigated IH, but also accelerated the regeneration of EC (re-endothelialization) in vivo in comparison to control groups (i.e., saline, free NAD⁺ solution, empty CaP-NP). Collectively, our current study provides proof-of-concept evidence supporting the role of targeted NAD⁺ repletion nanotherapy in managing restenosis and improving reendothelialization.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"376 ","pages":"Pages 806-815"},"PeriodicalIF":10.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501227","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":"Extracellular vesicles powered cancer immunotherapy: Targeted delivery of adenovirus-based cancer vaccine in humanized melanoma model","authors":"Sara Mathlouthi ,&nbsp;Lukasz Kuryk ,&nbsp;Marta Prygiel ,&nbsp;Maria Giovanna Lupo ,&nbsp;Aleksandra Anna Zasada ,&nbsp;Cristiano Pesce ,&nbsp;Nicola Ferri ,&nbsp;Beate Rinner ,&nbsp;Stefano Salmaso ,&nbsp;Mariangela Garofalo","doi":"10.1016/j.jconrel.2024.10.057","DOIUrl":"10.1016/j.jconrel.2024.10.057","url":null,"abstract":"<div><div>Malignant melanoma, a rapidly spreading form of skin cancer, is becoming more prevalent worldwide. While surgery is successful in treating early-stage melanoma, patients with advanced disease have only a 20 % chance of surviving beyond five years. Melanomas with mutations in the NRAS gene are characterized for a more aggressive tumor biology, poorer prognosis and shorter survival. Hence, new therapeutic strategies are needed, especially for this specific group of patients. Novel approaches, such as cancer vaccines, offer promising solutions by stimulating the anti-tumor immune response. Nevertheless, their clinical efficacy is still modest and more effective approaches are required. Herein, we propose the systemic administration of the adenovirus-based cancer vaccine complexed in extracellular vesicles (EVs) with the aim of achieving a targeted therapeutic effect. The vaccine was based on previously tested oncolytic adenovirus Ad5/3-D24-ICOSL-CD40L in combination with melanoma-specific antigens targeting NRAS mutations to enhance the anticancer effect. The antineoplastic properties of the oncolytic vaccine were evaluated in xenograft MUG Mel-2 melanoma BALB/c nude mice. Moreover, to mimic the tumor microenvironment, while investigating at the same time immune cell infiltration and drug penetration, we established a 3D co-culture model based on human NRAS mutated MUG Mel-2 spheroids and PBMCs (HLA matched), which displayed a synergistic effect when treated with the cancer vaccine compared to relative controls. Subsequently, we investigated the systemic delivery of the vaccine in EV formulations in a humanized NSG MUG Mel-2 melanoma mouse model. Our study provides a promising strategy for a tumor-targeted vaccine delivery by EVs, resulting in improved anticancer efficacy and increased infiltration of tumor-infiltrating lymphocytes. This study explores the potential of EVs for the selective delivery of cancer vaccines against malignancies, such as NRAS melanoma. Overall, this research could pave the way for applying autologous EVs as a safe and efficacious tool for targeted cancer therapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"376 ","pages":"Pages 777-793"},"PeriodicalIF":10.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557982","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":"Immunomodulatory microneedle patch for enhanced Ferroptosis and immunogenic cell death in postoperative tumor therapy","authors":"Yuqin Wang ,&nbsp;Quanmin Wang ,&nbsp;Qingguo Zhong ,&nbsp;Yanteng Xu ,&nbsp;Chunxiong Zheng ,&nbsp;Mingqiang Li ,&nbsp;Yu Tao ,&nbsp;Enguo Ju","doi":"10.1016/j.jconrel.2024.10.042","DOIUrl":"10.1016/j.jconrel.2024.10.042","url":null,"abstract":"<div><div>Microneedle technologies have emerged as a promising transdermal drug delivery platform for postoperative tumor therapy. Despite their potential, enhancing intracellular drug delivery to tumor cells and boosting the therapeutic efficiency of microneedles pose significant challenges. Herein, we develop a nanomedicine-loaded microneedle to enhance the induction of ferroptosis and immunogenic cell death for postoperative tumor therapy. This advancement is achieved by pre-formulating small molecule drugs with transition metal and protein templates into nanomedicine. Upon insertion into the tumors, the microneedle rapidly dissolves, facilitating the release and subsequent cellular uptake of the nanomedicine by tumor cells. Notably, the nanomedicine can release Mn ions and ferroptosis-inducer sulfasalazine (SAS) under acidic conditions. Furthermore, the released Mn ions can produce reactive oxygen species, which decrease the levels of glutathione (GSH) and glutathione peroxidase 4 (GPX4) with increased lipid peroxidation and enhanced induction of ferroptosis. Besides, the treatment stimulates immunogenic cell death through the cell surface exposure of calreticulin (CRT) and release of high-mobility group box 1 (HMGB1), which further stimulates dendric cell maturation, T cell infiltration, and macrophage polarization towards the M1 phenotype. Consequently, this strategy significantly inhibits postoperative tumor regrowth and extends overall survival. Our study indicates the potential of the combination of nanomedicine and microneedle to improve postoperative therapeutic efficiency.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"376 ","pages":"Pages 766-776"},"PeriodicalIF":10.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488234","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 rapamycin and inhibition of platelet adhesion with multifunctional peptide nanoparticles for atherosclerosis treatment","authors":"Anqi Wang ,&nbsp;Kai Yue ,&nbsp;Weishen Zhong ,&nbsp;Genpei Zhang ,&nbsp;Xinxin Zhang ,&nbsp;Lei Wang","doi":"10.1016/j.jconrel.2024.10.051","DOIUrl":"10.1016/j.jconrel.2024.10.051","url":null,"abstract":"<div><div>There is increasing evidence supporting the unique benefits of targeted therapy in treating atherosclerotic disease. Given the complex nature of atherosclerosis development, we proposed a novel strategy for the efficient delivery of rapamycin (RAPA) by targeting both the exposed subendothelial collagen and oxidized low-density lipoprotein (oxLDL) present in plaques. In response, we developed multifunctional peptide (MP) nanoparticles for targeted drug delivery. The ability of MP nanoparticles to load RAPA and target collagen/oxLDL was investigated through molecular dynamics simulations and in vitro experiments. The efficacy of MP nanoparticles in atherosclerosis treatment was assessed via in vivo experiments on ApoE^−/− mice. Results indicate that MP nanoparticles have encapsulation and drug loading efficiencies for RAPA of 78.3 % and 43.9 %, respectively. By targeting collagen, MP nanoparticles create steric hindrance that inhibits 77.2 % of platelet adhesion. These nanoparticles can also target oxLDL, delivering RAPA into plaques and significantly reducing macrophage uptake of oxLDL. In vivo experiments showed that MP nanoparticles effectively targeted and accumulated in plaques. Treating mice with MP@RAPA nanoparticles for 10 weeks led to an 81.3 % reduction in the aortic vascular plaque area and decreased concentrations of MCP-1, hs-CRP, MMP-1, P-selectin, IL-1β, and IL-8 inflammatory factors, as well as the optical density of platelet-associated proteins (CD42, CD61, and PECAM-1). These results highlight the promising potential of MP nanoparticles for atherosclerotic disease treatment.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"376 ","pages":"Pages 753-765"},"PeriodicalIF":10.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555776","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":"Recent advances in liposomes and peptide-based therapeutics for glioblastoma treatment","authors":"M.-A. Jourdain,&nbsp;J. Eyer","doi":"10.1016/j.jconrel.2024.10.037","DOIUrl":"10.1016/j.jconrel.2024.10.037","url":null,"abstract":"<div><div>In the context of glioblastoma treatment, the penetration of drugs is drastically limited by the blood-brain-barrier (BBB). Emerging therapies have focused on the field of therapeutic peptides for their excellent BBB targeting properties that promote a deep tumor penetration. Peptide-based strategies are also renowned for their abilities of driving cargo such as liposomal system allowing an active targeting of receptors overexpressed on GBM cells. This review provides a detailed description of the internalization mechanisms of specific GBM homing and penetrating peptides as well as the latest in vitro<em>/</em>in vivo studies of liposomes functionalized with them. The purpose of this review is to summarize a selection of promising pre-clinical results that demonstrate the advantages of this nanosystem, including an increase of tumor cell targeting, triggering drug accumulation and thus a strong antitumor effect. Aware of the early stage of these studies, many challenges need to be overcome to promote peptide-directed liposome at clinical level. In particular, the lack of suitable production, the difficulty to characterize the nanosystem and therapeutic competition leaded by antibodies.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"376 ","pages":"Pages 732-752"},"PeriodicalIF":10.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488206","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":"Drug conjugates crosslinked bioresponsive hydrogel for combination therapy of diabetic wound","authors":"Manhui Zheng ,&nbsp;Wenxiang Song ,&nbsp;Peipei Huang ,&nbsp;Yueping Huang ,&nbsp;Hanxuan Lin ,&nbsp;Miao Zhang ,&nbsp;Huacheng He ,&nbsp;Jiang Wu","doi":"10.1016/j.jconrel.2024.10.046","DOIUrl":"10.1016/j.jconrel.2024.10.046","url":null,"abstract":"<div><div>Basic fibroblast growth factor (bFGF) has proved to be effective for wound healing, yet its effectiveness is extremely retarded in diabetic wounds due to the severe oxidative stress in wound beds. To solve this issue, herein a novel combination therapy of bFGF and <em>N</em>-acetylcysteine (NAC, antioxidant) was devised for improved diabetic wound repair. To avoid rapid loss of both drugs in the wound beds, a bioresponsive hydrogel (bFGF-HSPP-NAC) was engineered by incorporating bFGF and NAC into polymer-drug conjugates (HSPP) <em>via</em> thiol-disulfide exchange reactions. In response to oxidative stress (<em>e.g.</em>, reactive oxygen species), the disulfide bonds (<em>S<img>S</em>) within the hydrogel are broken into thiol groups (<em>-S-H</em>), thereby promoting hydrogel degradation and enabling controlled drug release. Initially, NAC is released to scavenge free radicals and ameliorate oxidative damage. Subsequently, bFGF is released to expedite tissue regeneration. This combinatorial strategy is tailored to the specific characteristics of the wound microenvironment at various stages of diabetic wound healing, thereby achieving therapeutic efficacy. The results indicate that the bFGF-HSPP-NAC hydrogel markedly enhances re-epithelialization, collagen deposition, hair follicle regeneration, and neovascularization. In conclusion, the bioresponsive bFGF-HSPP-NAC hydrogel demonstrates significant potential for application in combinatorial therapeutic approaches for diabetic wound healing.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"376 ","pages":"Pages 701-716"},"PeriodicalIF":10.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490514","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":"A bifunctional nanocomplex with remineralizing and antibacterial activities to interrupt dental caries","authors":"Cheng Zhi ,&nbsp;Xu Chen ,&nbsp;Kaining Yu ,&nbsp;Min Li ,&nbsp;Fan Li ,&nbsp;Yangyang Ye ,&nbsp;Yanyun Pang ,&nbsp;Ye Zhang ,&nbsp;Xiangyu Zhang ,&nbsp;Xu Zhang","doi":"10.1016/j.jconrel.2024.10.041","DOIUrl":"10.1016/j.jconrel.2024.10.041","url":null,"abstract":"<div><div>Dental caries result from an imbalance between the demineralization and remineralization of dental hard tissues, primarily caused by biofilm accumulation. According to the theory of interrupting dental caries, effective anticaries materials and techniques should possess both remineralizing and antibacterial properties. However, current anticaries materials fail to mimic the process of amelogenesis to achieve remineralization while inhibiting the adhesion of cariogenic bacteria and the formation of biofilms. In this study, silk fibroin (SF) loaded with benzalkonium chloride (BZC) successfully formed an SF-BZC composite. This composite stabilized amorphous calcium phosphate (ACP), creating an ACP@SF-BZC dual-functional nanocomplex with both remineralizing and antibacterial properties. ACP@SF-BZC demonstrated significant anti-adhesion and biofilm inhibitory effects against <em>Streptococcus mutans</em> and <em>Streptococcus sobrinus</em>. Moreover, compared to fluoride, ACP@SF-BZC significantly enhanced the remineralization of demineralized enamel surfaces, forming a stable remineralized layer with improved mechanical properties, both in vitro and in vivo. In summary, the dual-function ACP@SF-BZC nanocomplex, with its remineralizing and antibacterial effects, offers a promising alternative for preventing and arresting enamel caries.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"376 ","pages":"Pages 717-731"},"PeriodicalIF":10.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501226","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":"A single molecule carrier for ocular posterior segment diseases","authors":"Xiao-Ling Zhang, Yu-Xin Yue, Yang Yang, An-Kang Ying, Rong Ma, Jie Chen, Fang-Yuan Chen, Xiao-Yun Hou, Yu-Chen Pan, Da-Zhuang Ren, Tao Yang, Zhi-Qing Li, Dong-Sheng Guo","doi":"10.1016/j.jconrel.2024.10.052","DOIUrl":"https://doi.org/10.1016/j.jconrel.2024.10.052","url":null,"abstract":"Eye drops are envisaged as the most promising non-invasive formulation for the treatment of the ocular posterior segment diseases, while it is hindered by a series of complex ocular barriers, both static and dynamic in nature. In this context, we propose a single molecule nanomedicine based on host-guest chemistry to achieve highly efficient drug delivery targeted to ocular posterior segment. Sulfonated azocalix[4]arene (SAC4A) serves as the single molecule carrier, owing the multiple features of small size (24.0 Å in length, 21.2 Å in width, 14.8 Å in height with a Van der Waals volume of 930 Å³), negative charge, hydrophilicity, loading universality and hypoxia-triggered release. As a proof-of-concept, an eye drop formed by the complexation of SAC4A with sunitinib (SUN) is prepared to treat wet age-related macular degeneration (wAMD). SAC4A successfully transports SUN to the ocular posterior segment (the amount of SUN reaching the retinal-choroid tissue in the SUN@SAC4A group was 2.47 times larger than that in the SUN group at 30 min), significantly enhancing its anti-choroidal neoangiogenesis effect of SUN to wAMD, which played a key role in the treatment. We believe that the single molecule nanomedicine paradigm is highly amenable for treating various ocular posterior segment diseases in the future.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"37 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541490","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":"Optimizing lipid nanoparticles for fetal gene delivery in vitro, ex vivo, and aided with machine learning","authors":"Amr Abostait ,&nbsp;Mahmoud Abdelkarim ,&nbsp;Zeqing Bao ,&nbsp;Yuichiro Miyake ,&nbsp;Wai Hei Tse ,&nbsp;Caterina Di Ciano-Oliveir ,&nbsp;Tina Buerki-Thurnherr ,&nbsp;Christine Allen ,&nbsp;Richard Keijzer ,&nbsp;Hagar I. Labouta","doi":"10.1016/j.jconrel.2024.10.047","DOIUrl":"10.1016/j.jconrel.2024.10.047","url":null,"abstract":"<div><div>There is a clinical need to develop lipid nanoparticles (LNPs) to deliver congenital therapies to the fetus during pregnancy. The aim of these therapies is to restore normal fetal development and prevent irreversible conditions after birth. As a first step, LNPs need to be optimized for transplacental transport, safety on the placental barrier and fetal organs and transfection efficiency. We developed and characterized a library of LNPs of varying compositions and used machine learning (ML) models to delineate the determinants of LNP size and zeta potential. Utilizing different in vitro placental models with the help of a Random Forest algorithm, we could identify the top features driving percentage LNP transport and kinetics at 24 h, out of a total of 18 input features represented by 41 LNP formulations and 48 different transport experiments. We further evaluated the LNPs for safety, placental cell uptake, transfection efficiency in placental trophoblasts and fetal lung fibroblasts. To ensure the integrity of the LNPs following transplacental transport, we screened LNPs for transport and transfection using a high-throughput integrated transport-transfection in vitro model. Finally, we assessed toxicity of the LNPs in a tracheal occlusion fetal lung explant model. LNPs showed little to no toxicity to fetal and placental cells. Immunoglobin G (IgG) orientation on the surface of LNPs, PEGylated lipids, and ionizable lipids had significant effects on placental transport. The Random Forest algorithm identified the top features driving LNPs placental transport percentage and kinetics. Zeta potential emerged in the top driving features. Building on the ML model results, we developed new LNP formulations to further optimize the transport leading to 622 % increase in transport at 24 h versus control LNP formulation. To induce preferential siRNA transfection of fetal lung, we further optimized cationic lipid percentage and the lipid-to-siRNA ratio. Studying LNPs in an integrated placental and fetal lung fibroblasts model showed a strong correlation between zeta potential and fetal lung transfection. Finally, we assessed the toxicity of LNPs in a tracheal occlusion lung explant model. The optimized formulations appeared to be safe on ex vivo fetal lungs as indicated by insignificant changes in apoptosis (Caspase-3) and proliferation (Ki67) markers. In conclusion, we have optimized an LNP formulation that is safe, with high transplacental transport and preferential transfection in fetal lung cells. Our research findings represent an important step toward establishing the safety and effectiveness of LNPs for gene delivery to the fetal organs.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"376 ","pages":"Pages 678-700"},"PeriodicalIF":10.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490563","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":"Allan Hoffman - My friend.","authors":"James M Anderson","doi":"10.1016/j.jconrel.2024.10.022","DOIUrl":"https://doi.org/10.1016/j.jconrel.2024.10.022","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545737","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}