AUTHOR=Li Qing-qing , Yan Jia-hui , Zhou Zhi-e , Geng Xiang , Xiong Jian-hua 

TITLE=Enhanced anti-inflammatory activity of chlorogenic acid via folic acid-TPGS-modified liposomes encapsulation: characterization and In vivo evaluation on colitis mice

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1437773

DOI=10.3389/fphar.2024.1437773

ISSN=1663-9812

ABSTRACT=<sec><title>Introduction</title><p>Chlorogenic acid (CGA) has been identified to possess salient anti-inflammatory, antioxidant, and anticancer attributes. However, its application is limited by its instability and low bioavailability. Liposomes have been considered effective pharmaceutical delivery vehicles due to their ability to continuously release loaded drugs, improve drug stability, and display good biocompatibility. They can be easily modified by other small molecules to acquire additional biological functions. In this study, we developed and characterized folic acid-TPGS-modified chlorogenic acid liposome (FTCLP) and evaluated its anti-inflammatory activity.</p></sec><sec><title>Methods</title><p>The successful encapsulation of CGA within FTCLP was confirmed through examination using electron microscopy, fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The <italic>in vitro</italic> release characteristics of FTCLP were evaluated using the dialysis bag membrane method. Meanwhile, a dextran sulfate sodium (DSS) -induced colitis model was employed to investigate the anti-inflammatory effect of FTCLP and its mechanism.</p></sec><sec><title>Results</title><p>The FTCLP exhibited an encapsulation efficiency (EE) of 84.85 ± 1.20% and a drug loading (DL) of 11.67 ± 0.04%. The particle size of FTCLP was determined to be 150.63 ± 0.71 nm, with a polydispersity index (PDI) of 0.198 ± 0.02 and a zeta potential of 2.61 ± 0.38 mV. The <italic>in vitro</italic> release profile followed the Higuchi model, indicating sustained-release characteristics. The <italic>in vivo</italic> study demonstrated that FTCLP treatment was effective in improving the symptoms of DSS-induced inflammatory response, as evidenced by mitigation of weight loss, reduction in the disease activity index (DAI) score, restoration of colon length, and attenuation of colon tissue damage. Furthermore, the levels of pro-inflammatory cytokines, including interferon-gamma (INF-γ), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), were markedly diminished in both the serum and colon tissue. FTCLP was also observed to suppress the expression of <italic>INF-γ</italic>, <italic>IL-1β</italic>, <italic>IL-6</italic>, tumor necrosis factor-alpha (<italic>TNF-α</italic>), and nuclear factor kappa B (<italic>NF-κB</italic>) <italic>p65</italic>, while concomitantly upregulating the expression of Janus kinase (<italic>JAK</italic>) and signal transducer and activator of transcription 3 (<italic>STAT3</italic>). Besides, the administration of FTCLP was found to result in an increase in the abundance of <italic>Lactobacillaceae</italic> and <italic>Peptostreptococcaceae</italic>, while decreasing the abundance of <italic>Bacteroidaceae</italic>, <italic>Rikenellaceae</italic>, and <italic>Helicobacteraceae</italic>.</p></sec><sec><title>Conclusion</title><p>Following encapsulation of CGA within liposomes, FTCLP revealed favorable stability and sustained release properties, and enhanced the anti-inflammatory effects by modulating multiple inflammation-related biomarkers. FTCLP has the potential to be a safe and effective drug for targeted therapy of colitis.</p></sec>