通讯机构：
[Tang, Chao-Ke] U;Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.
关键词：
Cholesterol transport system;Atherosclerosis;High-density lipoprotein
摘要：
Atherosclerosis, the pathological basis of most cardiovascular disease (CVD), is closely associated with cholesterol accumulation in the arterial intima. Excessive cholesterol is removed by the reverse cholesterol transport (RCT) pathway, representing a major antiatherogenic mechanism. In addition to the RCT, other pathways are required for maintaining the whole-body cholesterol homeostasis. Thus, we propose a working model of integrated cholesterol transport, termed the cholesterol transport system (CTS), to describe body cholesterol metabolism. The novel model not only involves the classical view of RCT but also contains other steps, such as cholesterol absorption in the small intestine, low-density lipoprotein uptake by the liver, and transintestinal cholesterol excretion. Extensive studies have shown that dysfunctional CTS is one of the major causes for hypercholesterolemia and atherosclerosis. Currently, several drugs are available to improve the CTS efficiently. There are also several therapeutic approaches that have entered into clinical trials and shown considerable promise for decreasing the risk of CVD. In recent years, a variety of novel findings reveal the molecular mechanisms for the CTS and its role in the development of atherosclerosis, thereby providing novel insights into the understanding of whole-body cholesterol transport and metabolism. In this review, we summarize the latest advances in this area with an emphasis on the therapeutic potential of targeting the CTS in CVD patients.
期刊：
International Journal of Pharmaceutics,2018年535(1-2):253-260 ISSN：0378-5173
通讯作者：
Zheng, Xing;Tang, Guotao
作者机构：
[Wang, Zhe; Deng, Xiangping; Tang, Guotao; Zheng, Xing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Ding, Jinsong; Zhou, Wenhu] Cent S Univ, Xiangya Sch Pharmaceut Sci, Changsha, Hunan, Peoples R China.;[Zheng, Xing; Tang, Guotao] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zheng, X; Tang, GT] U;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.
关键词：
pH-sensitive micelles;pH-sensitive release;release mechanism;targeted drug delivery system
摘要：
During the past decades, chemotherapy has been regarded as the most effective method for tumor therapy, but still faces significant challenges, such as poor tumor selectivity and multidrug resistance. The development of targeted drug delivery systems brings certain dramatic advantages for reducing the side effects and improving the therapeutic efficacy. Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for targeted therapy. Among these approaches, pH-sensitive micelles are regarded as the most general strategy with advantages of increasing solubility of water-insoluble drugs, pH-sensitive release, high drug loading, etc. This review will focus on the potential of pH-sensitive micelles in tumor therapy, analyze four types of drug-loaded micelles and mechanisms of drug release and give an exhaustive collection of recent investigations. Sufficient understanding of these mechanisms will help us to design more efficient pH-sensitive drug delivery system to address the challenges encountered in targeted drug delivery systems for tumor therapy.
