绿原酸载药类脂囊泡和前体泡囊:体外抗氧化和抗菌活性与伤口愈合疗效  

Chlorogenic acid loaded niosomes and proniosomes:in vitro antioxidant and antibacterial activities with efficacy in wound healing

作　　者：Hemangi Ramesh Trivedi Prashant Keshao Puranik 

机构地区：[1]Department of Pharmaceutical Sciences,Rashtrasant Tukadoji Maharaj Nagpur University,Nagpur,Maharashtra 440033,India

出　　处：《Digital Chinese Medicine》2023年第2期170-188,共19页数字中医药（英文）

摘　　要：目的开发和优化天然多酚绿原酸(CGA)的类脂囊泡和前体泡囊递送系统,以提高其理化性质和渗透性,从而可能增强其药理活性。方法已配制的CGA类脂囊泡(CGANs)和CGA前体泡囊(CGAPNs)用薄膜水化法和阶段分离凝聚法进行准备,对其粒子尺寸、形态学、包封率、Z电位、变形能力、体外扩散、离体渗透性和长期稳定性等不同属性进行描述。并使用体外抗氧化测定、抗菌测定和大鼠切除创面愈合模型进一步评价其效率。结果优化后的CGANs和CGAPNs呈球形囊泡状,粒径分别为(490.1±43.0)和(280.0±22.0)nm,多分散指数(PDI)值分别为0.526和0.173,稳定Z电位值分别为(−29.3±6.4)和(−33.2±6.5)mV。与普通CGA相比,CGANs和CGAPNs囊泡具有较高的包封率(98.27%±0.46%&97.27%±0.25%)和良好的变形性(8.77±0.22&6.87±0.17),更高的体外扩散率(97.96%±1.67%&91.00%±1.32%)和渗透系数值(67×10^(−3)±1.72&52×10^(−3)±1.09),具有长期的稳定性。二者均表现出增强的DPPH自由基清除和Fe2+螯合能力,且CGAPNs优于CGANs。与普通CGA相比,它们还表现出对不同革兰氏阳性和革兰氏阴性菌株的致死杀菌活性,最小抑菌浓度(MIC)值较低(低8倍和16倍)。与市售CGANs(92.89%)和CGA水凝胶(88.89%)相比,CGANPs(99.56%)和CGANs(98.44%)在第9天观察到收缩百分比较高的伤口面积显著减小(P<0.05)。结论这些结果显示CGANs和CGAPNs在局部伤口愈合应用中的巨大潜力。这是CGA在类脂囊泡和前体泡囊局部给药系统中的首个研究。Objective To develop and optimize niosomal and proniosomal vesicular delivery systems for a naturally occurring polyphenol chlorogenic acid(CGA),so as to improve its physicochemical properties and permeability,which may enhance its pharmacological activity.Methods The formulated CGA niosomes(CGANs)and CGA proniosomes(CGAPNs)were primed by thin film hydration and phase separation coacervation methods,and were characterized with different attributes including particle size,morphology,entrapment efficiency,zeta potential,deformability,in vitro diffusion,ex vivo permeability,and long-term stability.Their efficiency was further evaluated with in vitro antioxidant assay,antibacterial assays,and excision wound healing model in rats.Results Optimized CGANs and CGAPNs showed spherical vesicles with particle size of 490.1±43.0 and 280.0±22.0 nm,polydispersity index(PDI)values of 0.526 and 0.173,and stable zeta potential values of-29.3±6.4 and-33.2±6.5 mV,respectively.The CGANs and CGAPNs vesicles showed higher entrapment(98.27%±0.46%&97.27%±0.25%)with good deformability(8.77±0.22&6.87±0.17),higher in vitro diffusion(97.96%±1.67%&91.00%±1.32%),and permeability coefficient values(67×10^(−3)±1.72&52×10^(−3)±1.09)with long-term stability in comparison with plain CGA.Enhanced 2-diphenyl-1-picrylhydrazyl(DPPH)radical scavenging and Fe2+chelation ability was obtained with CGAPNs>CGANs.They also demonstrated lethal bactericidal activity on different gram positive and gram negative strains with lower minimum inhibitory concentration(MIC)values(8×and 16×times less)as compared with plain CGA.Significant reduction(P<0.05)in wound area with higher wound contraction percentages on day 9 was observed with CGANPs(99.56%)>CGANs(98.44%)in comparison with marketed(92.89%)and CGA(88.89%)hydrogel.Conclusion These results show great potential of CGANs and CGAPNs for topical wound healing application.This is the first study of CGA in niosomal and proniosomal topical delivery systems.

关 键 词：绿原酸 类脂囊泡 前体泡囊 抗氧化剂 抗菌 伤口愈合 

分 类 号：R965[医药卫生—药理学]