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

Abstract

Purpose: 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.