■绿原酸(CGA)已被确定具有显着的抗炎作用,抗氧化剂,和抗癌属性。然而,它的应用受到其不稳定性和低生物利用度的限制。脂质体被认为是有效的药物递送载体,因为它们能够连续释放负载的药物。提高药物稳定性,并显示出良好的生物相容性。它们可以很容易地被其他小分子修饰以获得额外的生物学功能。在这项研究中,我们开发并表征了叶酸-TPGS修饰的绿原酸脂质体(FTCLP),并评估了其抗炎活性。
■通过电子显微镜检查证实了在FTCLP内成功封装CGA,傅里叶变换红外光谱(FTIR),和差示扫描量热法(DSC)。采用透析袋膜法评价FTCLP的体外释放特性。同时,采用葡聚糖硫酸钠(DSS)诱导的结肠炎模型,研究FTCLP的抗炎作用及其机制。
■FTCLP表现出84.85±1.20%的包封效率(EE)和11.67±0.04%的载药量(DL)。FTCLP的粒径确定为150.63±0.71nm,多分散指数(PDI)为0.198±0.02,ζ电位为2.61±0.38mV。体外释放曲线遵循Higuchi模型,表明缓释特性。体内研究表明,FTCLP治疗可有效改善DSS诱导的炎症反应症状,正如减轻体重减轻所证明的那样,疾病活动指数(DAI)评分降低,恢复结肠长度,和减轻结肠组织损伤。此外,促炎细胞因子的水平,包括干扰素-γ(INF-γ),白细胞介素-1β(IL-1β),和白细胞介素-6(IL-6),血清和结肠组织均明显减少。还观察到FTCLP抑制INF-γ的表达,IL-1β,IL-6,肿瘤坏死因子-α(TNF-α),和核因子κB(NF-κB)p65,同时上调Janus激酶(JAK)和信号转导和转录激活因子3(STAT3)的表达。此外,发现FTCLP的施用导致乳杆菌科和肽链球菌科的丰度增加,同时减少了拟杆菌科的丰度,Rikenellaceae,和螺旋杆菌科。
■在脂质体中包封CGA后,FTCLP显示出良好的稳定性和持续释放特性,并通过调节多种炎症相关的生物标志物增强抗炎作用。FTCLP有望成为一种安全有效的结肠炎靶向治疗药物。
UNASSIGNED: 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.
UNASSIGNED: 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 in vitro 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.
UNASSIGNED: 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 in vitro release profile followed the Higuchi model, indicating sustained-release characteristics. The in vivo 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 INF-γ, IL-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) p65, while concomitantly upregulating the expression of Janus kinase (JAK) and signal transducer and activator of transcription 3 (STAT3). Besides, the administration of FTCLP was found to result in an increase in the abundance of Lactobacillaceae and Peptostreptococcaceae, while decreasing the abundance of Bacteroidaceae, Rikenellaceae, and Helicobacteraceae.
UNASSIGNED: 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.