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

• Published in: Biomedicines Vol. 8; no. 12; p. 563
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02-12-2020; MDPI
• Subjects: 3-D printers; Animal models; Body weight; Clinical medicine; Coconut oil; Colitis; Colon; Computed tomography; Design; Drug delivery systems; Drug dosages; Inflammatory bowel disease; Inflammatory bowel diseases; Intestine; Lipids; M3dimaker; PET/CT imaging; Pharmaceuticals; rectal drug delivery; Rectum; Remission; Statistical analysis; Tacrolimus; three-dimensional printing; TNBS rat model; ulcerative colitis; United Kingdom > UK; United States > US; Spain; M3dimaker; personalized medicines and pharmaceuticals; PET/CT imaging; three-dimensional printing; rectal drug delivery; TNBS rat model; 3D printed drug products; ulcerative colitis
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines8120563

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.