Frontiers in drug delivery最新文献

{"title":"Dual conjugation of magnetic nanoparticles with antibodies and siRNA for cell-specific gene silencing in vascular cells.","authors":"Katarzyna Karpinska, Lin Li, Tao Wang","doi":"10.3389/fddev.2024.1416737","DOIUrl":"10.3389/fddev.2024.1416737","url":null,"abstract":"<p><p>RNA therapy is a rapidly expanding field and has great promise in achieving targeted gene silencing and contributing to personalized medicine. However, the delivery of RNA molecules into targeted organs or cells is still challenging. To overcome this hurdle, a number of nanocarriers with pros and cons have been developed. This study was designed to develop a simple and cost-effective approach to functionalize biodegradable magnetic iron nanoparticles (MNPs) for cell-specific siRNA delivery. MNPs were synthesized based on co-precipitation and further functionalized with sodium citrate and polyethyleneimine (PEI) followed by material characterization using TEM, FTIR, and Zeta potential. The citrate and PEI-coated MNPs were further conjugated with CD31 antibody and complexed with siRNA using a linker-free approach. siRNA-loaded MNPs successfully knocked down the expression of <i>GAPDH</i> in human endothelial cells (ECs) and <i>NOTCH3</i> in human vascular smooth muscle cells (VSMCs). In an EC and VSMC co-culture system under shear stress to mimic blood flow, siRNA and CD31 conjugated MNPs specifically targeted and delivered siRNA into the ECs. Our approach represents a versatile platform that could be adopted for targeted general siRNA delivery.</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"4 ","pages":"1416737"},"PeriodicalIF":0.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies and delivery systems for cell-based therapy in autoimmunity","authors":"M. Puccetti, Claudio Costantini, A. Schoubben, S. Giovagnoli, Maurizio Ricci","doi":"10.3389/fddev.2024.1436842","DOIUrl":"https://doi.org/10.3389/fddev.2024.1436842","url":null,"abstract":"This review article explores the potential of engineering antigen-presenting cells (APCs) for the immunotherapy of autoimmune diseases. It discusses various strategies for modifying APCs to induce antigen-specific tolerance, thereby mitigating autoimmune responses. The review covers recent advancements in APC engineering techniques, including genetic modification and nanoparticle-based approaches, and evaluates their efficacy in preclinical models and clinical trials. Additionally, challenges and future directions for the development of APC-based immunotherapies for autoimmunity – and other forms of cell-based immunotherapy – are discussed. Along this direction, this review (i) describes various strategies for engineering APCs, including genetic modification, nanoparticle delivery systems, and ex vivo manipulation techniques; (ii) discusses the selection of target antigens and the design of APC-based immunotherapies, and (iii) reviews preclinical models used to evaluate the efficacy and safety of engineered APCs in inducing antigen-specific tolerance.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"14 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum: Core-shell 3D printed biodegradable calcium phosphate cement - Alginate scaffolds for possible bone regeneration applications.","authors":"Clara Schweiker, Sergej Zankovic, Anna Baghnavi, Dirk Velten, Hagen Schmal, Ralf Thomann, Michael Seidenstuecker","doi":"10.3389/fddev.2024.1452132","DOIUrl":"10.3389/fddev.2024.1452132","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fddev.2024.1407304.].</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"4 ","pages":"1452132"},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary results on novel adjuvant combinations suggest enhanced immunogenicity of whole inactivated pandemic influenza vaccines","authors":"Allegra Peletta, Aurélie Marmy, Samo Guzelj, Alcidia Ramos Barros, Ž. Jakopin, Gerrit Borchard","doi":"10.3389/fddev.2024.1382266","DOIUrl":"https://doi.org/10.3389/fddev.2024.1382266","url":null,"abstract":"Due to the inherent risk of a further pandemic influenza outbreak, there is a need and growing interest in investigating combinations of prophylactic vaccines and novel adjuvants, particularly to achieve antigen dose sparing and improved immunogenicity. Influenza is a highly variable virus, where the specific vaccine target is constantly changing, representing a major challenge to influenza vaccine development. Currently, commercial inactivated influenza vaccines have a poor CD8+ T response, which impacts cross-reactivity and the duration of response. Adjuvanted influenza vaccines can increase immune responses, thereby achieving better protection and cross-reactivity to help contain the spread of the disease. An early exploration of a hybrid cholesterol-PLGA nanoparticle delivery system containing the saponin tomatine and a NOD2 (nucleotide-binding oligomerization domain 2) agonist called SG101 was conducted. This combination was preliminarily evaluated for its ability to induce cellular immunity when combined with whole inactivated virus (WIV) influenza vaccine. After the adjuvants were manufactured using a single emulsion process, two formulations with different drug loadings were selected and physico-chemically characterized, showing sizes between 224 ± 32 and 309 ± 45 nm and different morphologies. After ensuring the lack of in vitro toxicity and hemolytic activity, a pilot in vivo assay evaluated the hybrid nanoparticle formulation for its ability to induce humoral and cellular immunity when combined with whole inactivated virus (WIV) H5N1 influenza vaccine by intramuscular administration in mice. Hemagglutinin inhibition (HAI) titers for adjuvanted groups showed no significant difference compared to the group vaccinated with the antigen alone. It was similar for CD4+ and CD8+ T cell responses, although the high drug loading formulation induced higher titers of IFNγ-positive CD8+ T cells. These proof-of-concept results encourage further investigations to develop the hybrid formulation with increased or different loading ratios, to investigate manufacturing optimization, and to evaluate the role of the individual immunostimulatory compounds in immune responses.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"6 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141640751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of P-glycoprotein overexpression in brain endothelial cells as a model to study blood-brain barrier efflux transport","authors":"Sarah F. Hathcock, Hallie E. Knight, Emma G. Tong, Alexandra E. Meyer, Henry D. Mauser, Nadine Vollmuth, Brandon J. Kim","doi":"10.3389/fddev.2024.1433453","DOIUrl":"https://doi.org/10.3389/fddev.2024.1433453","url":null,"abstract":"The blood-brain barrier (BBB) is comprised of specialized brain endothelial cells (BECs) that contribute to maintaining central nervous system (CNS) homeostasis. BECs possess properties such as an array of multi-drug efflux transporters that eject various drugs and toxins, preventing their entry into the CNS. Together, it is estimated that these efflux transporters can eject up to 98% of known xenobiotic compounds. P-glycoprotein (P-gp) is a promiscuous efflux transporter at the BBB and can efflux up to 90 various substrates, representing a major hurdle in CNS drug delivery for therapeutic interventions. This necessitates the study of P-gp to discover drugs that are non-substrates of P-gp as well as to identify novel P-gp inhibitors. Here we report the generation of P-gp overexpressing BECs under the endogenous promoter control that could be used in the screening of P-gp substrates. These cells could provide utility in the design of drugs or identification of novel inhibitors.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141677182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microneedle-enhanced drug delivery: fabrication, characterization, and insights into release and permeation of nanocrystalline imiquimod.","authors":"Sophie Luise Meiser, Jonas Pielenhofer, Ann-Kathrin Hartmann, Lara Stein, Jule Dettweiler, Stephan Grabbe, Markus P Radsak, Peter Langguth","doi":"10.3389/fddev.2024.1425144","DOIUrl":"10.3389/fddev.2024.1425144","url":null,"abstract":"<p><p>Transcutaneous delivery systems bear several advantages over conventional needle-based injections. Considering the low bioavailability and poor water-solubility of imiquimod, a manufacturing process has been developed to incorporate imiquimod as suspended nanocrystals in different formulations. In this study, three formulations - fast-dissolving microneedle arrays that contain nanocrystalline imiquimod in a poly (vinyl)alcohol matrix and two semisolid preparations-were characterized and compared. The results show that microneedle arrays have an advantage over the semisolid preparations regarding <i>in vitro</i> release and permeation characteristics. Microneedle arrays facilitate <i>ex vivo</i> permeation, thus reducing the applied dose by 93% compared to the semisolid formulations. Additionally, the amount of imiquimod permeated after 24 h maintained the same level even when the contact time of the formulation with the skin is less than 1 hour. In conclusion, our results highlight the great potential of advanced microneedle based delivery systems and foster the further evaluation of this approach.</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"4 ","pages":"1425144"},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-throughput drug screening to investigate blood-brain barrier permeability <i>in vitro</i> with a focus on breast cancer chemotherapeutic agents.","authors":"Carolin J Curtaz, Sophia Wucherpfennig, Emad Al-Masnaea, Saskia-Laureen Herbert, Achim Wöckel, Patrick Meybohm, Malgorzata Burek","doi":"10.3389/fddev.2024.1331126","DOIUrl":"10.3389/fddev.2024.1331126","url":null,"abstract":"<p><p>Therapy of cerebral diseases such as brain metastatic breast cancer is still challenging. Due to the blood-brain barrier (BBB), a tight barrier that protects the brain and prevents the passage of many drugs, therapeutically sufficient drug concentrations in the brain are often not achieved. Therefore, methods and drugs to manipulate the BBB permeability are required. Here we used high-throughput screening (HTS) to identify chemicals that may increase BBB permeability. Human BBB <i>in vitro</i> model derived from hematopoietic CD34⁺ stem cells (differentiated to brain-like endothelial cells, BLECs) was used. BLECs were seeded on 96-well plates coated with biotinylated gelatin, treated with respective chemicals for 24 h followed by addition of FITC-avidin for permeability estimation. Selected substances were further tested <i>in vitro</i> on BLECs. Cell viability, gene and protein expression were measured using CellTiter-Glo^®, qPCR and Western blot, respectively. From 1,278 compounds, we identified 175 substances that cause at least a 50 percent increase in BBB permeability. Two substances from the substance classes used in breast cancer therapy, GW2974 (tyrosine kinase inhibitor) and 4-amino-1,8-naphthalimide (ANI) (PARP inhibitor), were analyzed in more detail. ANI was nontoxic to BLECs, while GW2974 decreased or increased viability depending on the concentration used. Both compounds significantly increased BBB permeability and altered protein and mRNA expression in BLECs. Influencing the BBB permeability in patients with brain metastases could increase the response rate to systemic therapy. Using HTS, we were able to accurately and quickly identify compounds that increase BBB permeability and show that using this type of screening method can be applied to endothelial paracellular permeability testing.</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"4 ","pages":"1331126"},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SpheroMold: modernizing the hanging drop method for spheroid culture","authors":"Ana Paula Pereira Guimaraes, I. R. Calori, Hong Bi, Antonio Claudio Tedesco","doi":"10.3389/fddev.2024.1397153","DOIUrl":"https://doi.org/10.3389/fddev.2024.1397153","url":null,"abstract":"The hanging drop method is a cost-effective approach for 3D spheroid culture. However, obtaining numerous spheroids in a limited area becomes challenging due to the risk of droplet coalescence, primarly during Petri dish handling. In this study, we describe a general method to fabricate a 3D printing-based support called SpheroMold that facilitates Petri dish handling and enhances spheroid production per unit area. As a proof-of-concept, we designed a digital negative mold which comprised 37 pegs within a 13.52 cm2 area, and then printed it using stereolithography; the density of pegs can be adjusted according to user requirements. The SpheroMold was created by pouring the base and curing agent (10:1) (Sylgard® 184 silicone) into the mold, curing it at 80°C, and then attaching it to the lid of a Petri dish. Our SpheroMold effectively prevented droplet coalescence during Petri dish inversion, enabling the production of numerous 3D spheroids while simplifying manipulation. Unlike conventional techniques, our design also facilitated a larger volume of culture medium per drop compared to a standard Petri dish, potentially decreasing the necessity for frequent medium exchange to sustain cellular health and reducing labor intensity.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"46 28","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141384385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-printed weight holders design and testing in mouse models of spinal cord injury","authors":"Sara De Vincentiis, Francesca Merighi, Peter Blümler, Jose Gustavo De La Ossa Guerra, Mariachiara Di Caprio, Marco Onorati, Marco Mainardi, V. Raffa, Marina Carbone","doi":"10.3389/fddev.2024.1397056","DOIUrl":"https://doi.org/10.3389/fddev.2024.1397056","url":null,"abstract":"This paper details the comprehensive design and prototyping of a 3D-printed wearable device tailored for mouse models which addresses the need for non-invasive applications in spinal cord studies and therapeutic treatments. Our work was prompted by the increasing demand for wearable devices in preclinical research on freely behaving rodent models of spinal cord injury. We present an innovative solution that employs compliant 3D-printed structures for stable device placement on the backs of both healthy and spinal cord-injured mice. In our trial, the device was represented by two magnets that applied passive magnetic stimulation to the injury site. This device was designed to be combined with the use of magnetic nanoparticles to render neurons or neural cells sensitive to an exogenous magnetic field, resulting in the stimulation of axon growth in response to a pulling force. We show different design iterations, emphasizing the challenges faced and the solutions proposed during the design process. The iterative design process involved multiple phases, from the magnet holder (MH) to the wearable device configurations. The latter included different approaches: a “Fitbit”, “Belt”, “Bib”, and ultimately a “Cape”. Each design iteration was accompanied by a testing protocol involving healthy and injured mice, with qualitative assessments focusing on animal wellbeing. Follow-up lasted for at least 21 consecutive days, thus allowing animal welfare to be accurately monitored. The final Cape design was our best compromise between the need for a thin structure that would not hinder movement and the resistance required to maintain the structure at the correct position while withstanding biting and mechanical stress. The detailed account of the iterative design process and testing procedures provides valuable insights for researchers and practitioners engaged in the development of wearable devices for mice, particularly in the context of spinal cord studies and therapeutic treatments. Finally, in addition to describing the design of a 3D-printed wearable holder, we also outline some general guidelines for the design of wearable devices.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"25 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141110098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Core-shell 3D printed biodegradable calcium phosphate cement—Alginate scaffolds for possible bone regeneration applications","authors":"Clara Schweiker, Sergej Zankovic, Anna Baghnavi, Dirk Velten, Hagen Schmal, Ralf Thomann, Michael Seidenstuecker","doi":"10.3389/fddev.2024.1407304","DOIUrl":"https://doi.org/10.3389/fddev.2024.1407304","url":null,"abstract":"The core/shell 3D printing process using CPC and alginate is intended to create biodegradable scaffolds that have a similar stability to bone tissue and also offer sufficient and continuous antibiotic release. In this way, a patient-specific and patient-friendly process will be established, which should optimally support the human organism in its regeneration. To generate the best possible strength values, the printed scaffolds underwent various post-treatments and were then tested in a material test. The test methods included self-setting, storage in a drying cabinet with a water-saturated atmosphere at 37°C, followed by incubation in PBS, freeze-drying, and coating the samples with alginate. Additionally, a degradation test at pH 7.4 and pH 5 was carried out to test stability under in vitro conditions. It was shown that the untreated and freeze-dried samples failed at a maximum load of 30–700 N, while the remaining scaffolds could withstand a load of at least 2,000 N. At this failure load, most of the test series showed an average deformation of 43.95%. All samples, therefore, remained below the strength of cancellous bone. However, based on a 20% load after surgery, the coated scaffolds represented the best possible alternative, with a Young’s modulus of around 1.71 MPa. We were able to demonstrate that self-setting occurs in core-shell printed CPC/alginate scaffolds after only 1 day, and that mass production is possible. By coating with alginate, the compressive strength could be increased without the need for additional post-treatment. The mechanical strength was sufficient to be available as a scaffold for bone regeneration and additionally as a drug delivery device for future applications and experiments.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"39 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140966247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}