Eudragit-coated chitosan-tripterygium glycoside conjugate microspheres alleviate DSS-induced experimental colitis by inhibiting the TLR4/NF-κB signaling pathway - 13/01/23
Abstract |
Objective |
Tripterygium glycoside (TG) is a fat-soluble extract of Tripterygium wilfordii, with anti-inflammatory properties associated with TLR signaling pathways. This study constructed a targeted delivery system for experimental colitis, namely, eudragit (EuL)-coated chitosan (Ch)-TG conjugate microspheres (Ch-TG-MS/EuL), and evaluated its therapeutic efficacy and underlying mechanisms.
Methods |
Ch-TG-MS was fabricated using emulsification cross-linking technique and then coated with EuL to create Ch-TG-MS/EuL. Drug release properties were assessed using a dialysis model. Additionally, the therapeutic benefits of Ch-TG-MS/EuL on colonic inflammation and its specific effect on TLR4/NF-κB signaling in intestinal mucosa were evaluated in vivo using a DSS-induced murine colitis model.
Results |
The Ch-TG-MS/EuL microspheres appeared as yellow powders with a slightly enlarged shape, rough surface, and adhesions. The Ch-TG-MS/EuL formulations also exhibited high entrapment efficiency and drug loading rate. High-performance liquid chromatography revealed that Ch-TG-MS/EuL exhibited a less intense peak than free TG, confirming that the drug is contained within the formulation. Free TG displayed explosive release within the first 5 h of administration, while Ch-TG-MS/EuL prevented the pre-mature release of TG and exhibited controllable release up to 24 h. In vivo, noticeable amelioration of intestinal mucosal tissue destruction was achieved with Ch-TG-MS/EuL compared to free TG. Additionally, immunohistochemical and western blotting results revealed that Ch-TG-MS/EuL markedly down-regulated the expression of intestinal mucosal TLR4, MyD88, and NF-κB p65. Hence, Ch-TG-MS/EuL may ameliorate the colon inflammatory response by inhibiting the hyperactivation of TLR4/NF-κB signaling.
Conclusion |
Novel Ch-TG-MS/EuL preparation may represent a colonic delivery system for UC therapeutics by inhibiting TLR4/NF-κB hyperactivation.
Data availability |
All experimental data supporting the conclusions of this study are available from the corresponding author on reasonable request.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Highlights |
• | Ch-TG-MS/EuL has a high entrapment efficiency and high drug loading rate. |
• | TG is released in a slow and controlled manner from Ch-TG-MS/EuL over 24 h. |
• | Ch-TG-MS/EuL via oral gavage reduces intestinal mucosal tissue destruction in mice. |
• | Ch-TG-MS/EuL may improve colonic inflammation via inhibition of TLR4/NFκB signaling. |
Abbreviations : Ch, CMC, DAI, DSS, EE, EuL, HCTGM, H&E, HPLC, HTG, LCTGM, LE, LTG, MCTGM, MS, MTG, NF-κB, SASP, TG, TLR, UC
Keywords : Tripterygium glycoside, Chitosan, Colitis, Targeted delivery, Toll-like receptor 4, NF-κB
Plan
Vol 158
Article 114194- février 2023 Retour au numéro
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