Machine learning-enabled one-step fabrication of targeted emodin liposomes via novel micromixer: A breakthrough for ulcerative colitis therapy

Ulcerative colitis (UC), characterized by intestinal mucosal ulcers and impaired barrier function, has seen a rising global incidence. Existing clinical treatments often yield limited efficacy and notable side effects, highlighting an urgent need for safer and more effective therapeutic strategies. Emodin (EMO), a natural bioactive compound, exhibits potent anti-inflammatory properties and potential to repair intestinal barriers, but its clinical application is restricted by poor water solubility and low bioavailability.

Traditional liposome preparation methods, such as thin-film hydration, are cumbersome, time-consuming, and prone to batch-to-batch variations. While microfluidic technology offers precise control over liposome synthesis, conventional micromixers struggle with scaling up production due to insufficient mixing efficiency. Additionally, optimizing liposome particle size—affected by flow rate, solvent, and other parameters—relies heavily on empirical trials, which are time- and labor-intensive.

To address these challenges, Prof. Xueye Chen’s team integrated microfluidic technology with machine learning, achieving one-step synthesis of targeted emodin liposomes (Apt-EMO@Lip). Their novel micromixer (VGHM), combining bionic vein groove microstructures (VGM) and horseshoe-shaped split-recombination channels (HSM), boasts a mixing efficiency of 99.93%. Compared to traditional thin-film hydration, the preparation cycle is shortened to 1/20, with reduced costs, minimal batch-to-batch variation in particle size, and excellent reproducibility.

The team also developed a CNN-LSTM-Attention multivariate regression model optimized by the Newton-Raphson algorithm (NRBO), which predicts liposome particle size with high accuracy (R²=0.9574, RMSE=6.52 nm), providing an efficient tool for experimental parameter optimization.

"Apt-EMO@Lip demonstrates sustained release properties, with a 48-hour release rate of 58.62%," explained Associate Professor Cheng Bao, co-corresponding author. "It significantly inhibits the secretion of LPS-induced pro-inflammatory factors in RAW264.7 cells and accelerates intestinal epithelial barrier repair, alleviating UC pathological features through multiple mechanisms."

Prof. Xueye Chen emphasized, "This strategy bridges the gap between lab-scale synthesis and clinical translation of targeted liposomes. By combining high-efficiency microfluidics with intelligent prediction, we’ve laid a foundation for personalized UC therapy and scalable production of nano-drugs."

Moving forward, the team aims to optimize the liposome’s targeting efficiency and conduct preclinical trials, striving to translate this innovation into a safe and effective clinical therapy for UC patients.

This work was supported by Yantai Science and Technology Innovation Development Plan Key Basic Research Projects(2023JCYJ048)，Special Supporting Funds for Leading Talents above Provincial Level in Yantai(220-20230002),Young Taishan Scholars Program of Shandong Province of China(tsqn202103091), Shandong Provincial Natural Science Foundation(ZR2024ME052), Ludong University introduced talents and started funding project(LD22065), Project supported by the Young Scientists Fund of the National Natural Science Foundation of China (32202024), and Project supported by the Young Scientists Fund of Shandong Provincial Natural Science Foundation (ZR2024QC103).

About Nano Research

Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 7,000 articles. In 2024 InCites Journal Citation Reports, its 2024 IF is 9.0 (8.7, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.