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 (SUVmax), 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 SUVmax 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 (R2 = 71.48%) between SUVmax 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.
Highlights
Inflammatory bowel disease (IBD) is a chronic disorder of unknown aetiology that causes prolonged inflammation of the gastrointestinal (GI) tract
In the study semisolid extrusion 3-dimensional printing (3DP) was used to prepare 3D printed suppositories loaded with the drug tacrolimus and subsequently test the feasibility of this approach to treat experimental colitis in a TNBS rat model
The versatility of semisolid extrusion 3DP allowed the preparation of small self-emulsifying suppositories containing an exact dose of the drug with a size and shape adapted for their rectal administration in rats
Summary
Inflammatory bowel disease (IBD) is a chronic disorder of unknown aetiology that causes prolonged inflammation of the gastrointestinal (GI) tract. The aetiology of IBD remains to be fully elucidated, an interplay of luminal microbiota, external environment and disturbances in the immune responses are hypothesized to trigger the onset of the disease in a genetically susceptible host [2]. Conventional treatment of IBD is based on the topical and systemic use of 5-aminosalicylic acid, azathioprine and steroids. This first line of treatment does not always achieve remission of the disease. When this happens, biological treatments such as infliximab, tocilizumab or ustekinumab are used [3,4]. In cases where even these commercialized drugs are not sufficient to treat symptoms, pharmaceutical compounding is the last alternative to treat these patients [5]
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