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3D打印的他克莫司直肠制剂可改善炎症性肠病实验动物模型中的结肠炎。

3D Printed Tacrolimus Rectal Formulations Ameliorate Colitis in an Experimental Animal Model of Inflammatory Bowel Disease.

作者信息

Seoane-Viaño Iria, Gómez-Lado Noemí, Lázare-Iglesias Héctor, García-Otero Xurxo, Antúnez-López José Ramón, Ruibal Álvaro, Varela-Correa Juan Jesús, Aguiar Pablo, Basit Abdul W, Otero-Espinar Francisco J, González-Barcia Miguel, Goyanes Alvaro, Luzardo-Álvarez Asteria, Fernández-Ferreiro Anxo

机构信息

Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain.

Paraquasil Group, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain.

出版信息

Biomedicines. 2020 Dec 2;8(12):563. doi: 10.3390/biomedicines8120563.

DOI:10.3390/biomedicines8120563
PMID:33276641
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7761558/
Abstract

The aim of this study was to fabricate novel self-supporting tacrolimus suppositories using semisolid extrusion 3-dimensional printing (3DP) and to investigate their efficacy in an experimental model of inflammatory bowel disease. Blends of Gelucire 44/14 and coconut oil were employed as lipid excipients to obtain suppository formulations with self-emulsifying properties, which were then tested in a TNBS (2,4,6-trinitrobenzenesulfonic acid) induced rat colitis model. Disease activity was monitored using PET/CT medical imaging; maximum standardized uptake values (SUV), a measure of tissue radiotracer accumulation rate, together with body weight changes and histological assessments, were used as inflammatory indices to monitor treatment efficacy. Following tacrolimus treatment, a significant reduction in SUV was observed on days 7 and 10 in the rat colon sections compared to non-treated animals. Histological analysis using Nancy index confirmed disease remission. Moreover, statistical analysis showed a positive correlation (R = 71.48%) between SUV values and weight changes over time. Overall, this study demonstrates the effectiveness of 3D printed tacrolimus suppositories to ameliorate colitis and highlights the utility of non-invasive PET/CT imaging to evaluate new therapies in the preclinical area.

摘要

本研究的目的是使用半固体挤出三维打印（3DP）技术制备新型自支撑他克莫司栓剂，并在炎症性肠病实验模型中研究其疗效。采用Gelucire 44/14和椰子油的混合物作为脂质辅料，以获得具有自乳化特性的栓剂制剂，然后在三硝基苯磺酸（TNBS）诱导的大鼠结肠炎模型中进行测试。使用PET/CT医学成像监测疾病活动；最大标准化摄取值（SUV），一种衡量组织放射性示踪剂积累率的指标，连同体重变化和组织学评估，被用作炎症指标来监测治疗效果。在他克莫司治疗后，与未治疗的动物相比，在第7天和第10天观察到大鼠结肠切片中的SUV显著降低。使用南希指数进行的组织学分析证实疾病缓解。此外，统计分析表明SUV值与随时间的体重变化之间存在正相关（R = 71.48%）。总体而言，本研究证明了3D打印他克莫司栓剂改善结肠炎的有效性，并突出了非侵入性PET/CT成像在临床前领域评估新疗法的实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cf5/7761558/37d7a10b5625/biomedicines-08-00563-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cf5/7761558/13c05c9622c3/biomedicines-08-00563-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cf5/7761558/5f34a9eebd0d/biomedicines-08-00563-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cf5/7761558/d8b9a1f48f57/biomedicines-08-00563-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cf5/7761558/ed79aa2878f3/biomedicines-08-00563-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cf5/7761558/ce89c0f387d3/biomedicines-08-00563-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cf5/7761558/37d7a10b5625/biomedicines-08-00563-g010.jpg

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