Drug targeting to inflammation: Studies on antioxidant surface loaded diclofenac liposomes
Drug targeting to inflammation: Studies on antioxidant surface loaded diclofenac liposomes
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DOI：
10.1016/j.ijpharm.2011.05.031
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发表时间：
2011-07-29
影响因子：
5.8
通讯作者：
Apte, Shashank
中科院分区：
文献类型：
--
作者：
Jukanti, Raju;Devaraj, Gopinath;Apte, Shashank
炎症与增强的血管通透性、炎症标志物的产生和活性氧（ROS）的过度产生以及内源性抗氧化剂的消耗相关。从这些事件中获得线索的几种药物靶向炎症的方法已经发展出来。令人惊讶的是，尚未遵循在炎症部位利用丰富的氧化应激的药物靶向方法。抗氧化剂表面负载的脂质体可能通过氧化还原相互作用优先定位于高水平ROS存在的炎症部位。本研究采用大鼠肉芽肿气囊炎症模型，探讨抗氧化剂作为脂质体表面靶向配体的作用。我们开发了常规和抗氧化剂负载的双氯芬酸（DFS）脂质体（辅酶Q10和抗坏血酸棕榈酸酯），用于静脉给药，并表征了囊泡大小、zeta电位和包封率。体内药物靶向研究显示，与常规脂质体和药物溶液相比，载抗氧化剂的脂质体的AUC、DFS在气囊液（APF）中的治疗利用度和APF/血清DFS浓度比增加。这些有希望的结果表明，抗氧化剂作为一种可能的配体在药物靶向丰富的活性氧存在的网站的作用。(C)2011 Elsevier B. V.保留所有权利。
Inflammation is associated with enhanced vascular permeability, production of inflammatory markers and over production of reactive oxygen species (ROS) with depletion of endogenous antioxidants. Several drug targeting approaches to inflammation taking clues from these events have been evolved. Surprisingly, a drug targeting approach utilizing abundant oxidative stress at inflammatory site has not been followed. Antioxidant surface loaded liposomes might preferentially localize at inflammatory sites via redox interaction where at high level of ROS exist. The present study was focused to investigate the role of antioxidant as a targeting ligand on the surface of liposome employing rat granuloma air pouch model of inflammation. We developed conventional and antioxidant loaded diclofenac (DFS) liposomes (co-enzyme Q10 and ascorbyl palmitate) for i.v. administration and characterized for vesicle size, zeta potential and percent entrapment. In vivo drug targeting studies showed an increase in AUC, therapeutic availability of DFS in air pouch fluid (APF) and APF/serum DFS concentration ratios from antioxidant loaded liposomes compared to conventional liposomes and drug solution. The promising results suggest the role of antioxidant as a possible ligand in drug targeting to a site where at abundant ROS exist. (C) 2011 Elsevier B.V. All rights reserved.