Dual-Stage Targeted Oral Drug Loaded Nanostructured Lipid Carriers Enhance the Efficacy of Ulcerative Colitis

Meijia Liu, Junyi Cui, Hanqing Li, Jie Yang, Guoyun Liu State Key Laboratory of Macromolecular Drugs and Large-Scale Preparation, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng, Shandong, 252059, People’s Republic of ChinaCorrespondence: Guoyun Liu, Email [email protected] Jie Yang, Email [email protected]: Ulcerative colitis (UC) is a non-specific inflammatory intestinal disease with long course and easy recurrence, which is one of the refractory diseases. In the previous work, para-quinone methide compound p-QM- 1i was found to be a potential anti-UC drug in UC mice; however, its water solubility was poor, and the oral dosage was high. In this study, in response to these shortcomings, an oral, actively targeted, and drug-loaded nanostructured lipid carrier (NLC) was constructed, and the dual-stage targeted design was performed on it.Methods: Firstly, the p-QM- 1i-loaded NLC surface was modified with infliximab (IFX) (p-QM- 1i-IFX-NLC), which can target highly expressed TNF-α in inflammatory cells or tissues; secondly, p-QM- 1i-IFX-NLC was coated with Eudragit S100 (S100- 1i-IFX-NLC), which can achieve specific release in the colon and protect NLC from interference from the gastrointestinal environment.Results: The experimental results suggested that the dual-stage targeted design of S100- 1i-IFX-NLC can effectively increase the solubility of p-QM- 1i, allowing S100- 1i-IFX-NLC to target the colon and p-QM- 1i-IFX-NLC to target the inflammatory tissue, increasing the aggregation of p-QM- 1i in the colon, enhancing the efficacy of p-QM- 1i, reducing the usage of p-QM- 1i, and increasing safety.Conclusion: The construction of Eudragit S100-coated p-QM- 1i-loaded IFX-modified NLC (S100- 1i-IFX-NLC) was effective and can improve the therapeutic effect of free drugs on UC. Keywords: ulcerative colitis, nanostructured lipid carriers, target delivery, TNF-α, colon specific release