Machine learning-guided one-step fabrication of targeted emodin liposomes via novel micromixer for ulcerative colitis therapy

This study demonstrates a one-step synthesis strategy for fabricating aptamer-conjugated emodin liposomes (Apt-EMO@Lip) through the integration of microfluidic technology and machine learning. We developed a novel vein groove and horseshoe-shaped micromixer (VGHM) that synergistically combines biomimetic vein-groove microstructures (VGM) with horseshoe-shaped splitting-confluence channels (HSM), achieving exceptional mixing efficiency (99.93% at outlet). Both blank liposomes (Blank@Lip) and Apt-EMO@Lip prepared via VGHM display monodisperse size distributions with narrow polydispersity indices, along with superior in vitro stability and biocompatibility. Systematic investigation of microfluidic parameters reveals that flow rate ratio (FRR) and solvent selection critically influence liposomal characteristics, while total flow rate (TFR) shows negligible impact on nanoparticle synthesis. Compared with conventional thin-film hydration methods, the VGHM approach reduces liposome preparation time by 95% while maintaining equivalent physicochemical properties, significantly lowering production costs and establishing a more efficient platform for nanocarrier fabrication. Innovatively, we developed a CNN-LSTM-Attention multivariate regression model incorporating a Newton-Raphson-based optimization (NRBO) algorithm, achieving superior predictive accuracy for liposome size (R² = 0.9574, root-mean-square error (RMSE) = 6.52 nm). This machine learning framework provides an intelligent parameter optimization tool for nanomedicine development. In vitro experiments demonstrated that emodin-loaded liposomes (EMO@Lip) exhibited sustained-release properties (58.62% cumulative release over 48 h) and effectively suppressed lipopolysaccharide (LPS)-induced secretion of pro-inflammatory mediators (NO, tumor necrosis factor-α (TNF-α), IL-6, IL-1β)—in RAW264.7 macrophages. The Caco-2 scratch assay further confirms EMO@Lip's ability to enhance intestinal epithelial barrier repair and comprehensively ameliorate ulcerative colitis pathology. This strategy significantly enhances drug enrichment efficiency at inflammatory sites via aptamer modification, establishing a novel, efficient, and safe nanomedicine delivery platform for precision-targeted ulcerative colitis therapy. The modular design enables high-throughput continuous production, thereby demonstrating exceptional clinical translation potential and industrial scalability.