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局部注射治疗中明胶制剂的逆流减少。

Backflow reduction in local injection therapy with gelatin formulations.

机构信息

Department of Biomedical, R&D C-enter, Nitta Gelatin, Inc, Yao City, Osaka, Japan.

出版信息

Drug Deliv. 2024 Dec;31(1):2329100. doi: 10.1080/10717544.2024.2329100. Epub 2024 Mar 22.

Abstract

The local injection of therapeutic drugs, including cells, oncolytic viruses and nucleic acids, into different organs is an administrative route used to achieve high drug exposure at the site of action. However, after local injection, material backflow and side effect reactions can occur. Hence, this study was carried out to investigate the effect of gelatin on backflow reduction in local injection. Gelatin particles (GPs) and hydrolyzed gelatin (HG) were injected into tissue models, including versatile training tissue (VTT), versatile training tissue tumor-in type (VTT-T), and broiler chicken muscles (BCM), using needle gauges between 23 G and 33 G. The backflow material fluid was collected with filter paper, and the backflow fluid rate was determined. The backflow rate was significantly reduced with 35 μm GPs ( value < .0001) at different concentrations up to 5% and with 75 μm GPs ( value < .01) up to 2% in the tissue models. The reduction in backflow with HG of different molecular weights showed that lower-molecular-weight HG required a higher-concentration dose (5% to 30%) and that higher-molecular-weight HG required a lower-concentration dose (7% to 8%). The backflow rate was significantly reduced with the gelatin-based formulation, in regard to the injection volumes, which varied from 10 μL to 100 μL with VTT or VTT-T and from 10 μL to 200 μL with BCM. The 35 μm GPs were injectable with needles of small gauges, which included 33 G, and the 75 μm GPs and HG were injectable with 27 G needles. The backflow rate was dependent on an optimal viscosity of the gelatin solutions. An optimal concentration of GPs or HG can prevent material backflow in local injection, and further studies with active drugs are necessary to investigate the applicability in tumor and organ injections.

摘要

将治疗性药物(包括细胞、溶瘤病毒和核酸)局部注射到不同器官是一种给药途径,可使药物在作用部位达到高暴露量。然而,局部注射后可能会发生物质回流和副作用反应。因此,本研究旨在探讨明胶对局部注射中减少回流的效果。使用 23G 和 33G 之间的针规将明胶颗粒(GPs)和水解明胶(HG)注入包括多功能训练组织(VTT)、多功能训练组织肿瘤型(VTT-T)和肉鸡肌肉(BCM)在内的组织模型中。用滤纸收集回流材料液,并测定回流液率。在不同浓度下,35μm 的 GPs( 值<0.0001)可显著降低 5%的回流率,75μm 的 GPs( 值<0.01)可降低 2%的回流率。不同分子量 HG 的回流减少表明,低分子量 HG 需要更高浓度的剂量(5%至 30%),而高分子量 HG 需要较低浓度的剂量(7%至 8%)。在注射体积为 10μL 至 100μL 的 VTT 或 VTT-T 以及 10μL 至 200μL 的 BCM 时,基于明胶的制剂显著降低了回流率。35μm 的 GPs 可与 33G 等小口径针一起注射,75μm 的 GPs 和 HG 可与 27G 针一起注射。回流率取决于明胶溶液的最佳粘度。GP 或 HG 的最佳浓度可防止局部注射中的物质回流,需要进一步研究活性药物在肿瘤和器官注射中的适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c58/10962293/3a00dc3bc3e7/IDRD_A_2329100_F0001_C.jpg

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