Unimolecular Micelle-Based Hybrid System for Perivascular Drug Delivery Produces Long-Term Efficacy for Neointima Attenuation in Rats.
Unimolecular Micelle-Based Hybrid System for Perivascular Drug Delivery Produces Long-Term Efficacy for Neointima Attenuation in Rats.
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DOI：
10.1021/acs.biomac.7b00617
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发表时间：
2017-07-10
影响因子：
6.2
通讯作者：
Kent KC
中科院分区：
文献类型：
--
作者：
Chen G;Shi X;Wang B;Xie R;Guo LW;Gong S;Kent KC
目前，临床上还没有预防开放手术(如用于治疗限流性血管疾病的搭桥手术)后新生内膜引起的(再)狭窄的选择。血管周围给药是一个很有前途的策略，但在转译研究中，获得长期(例如，3个月)抗(再)狭窄疗效仍然是一个主要挑战。在这项研究中，我们设计了一种独特的给药系统，由只有共价键的单个多臂星形两亲嵌段共聚物形成耐用的单分子胶束，以及由聚丙交酯-乙交酯-聚乙二醇-聚丙交酯-乙交酯三嵌段共聚物形成的温敏水凝胶(简称三嵌段凝胶)，体外稳定约4周。悬浮在三嵌段凝胶中的单分子药物胶束能够维持雷帕霉素4个月以上的释放。值得注意的是，即使在大鼠血管周围应用雷帕霉素胶束三块凝胶3个月后，与空白胶束/凝胶对照组(未用药)相比，动脉内膜/中膜面积比(再狭窄指标)仍受到80%的抑制。仅在三块凝胶中应用雷帕霉素是不能实现这一点的，因为它只使内膜/中膜比减少了27%。综上所述，我们创建了一种新的UM/Triblock凝胶杂化系统用于血管周围给药，在动物实验中取得了罕见的3个月抑制再狭窄的壮举。该系统显示出真正的潜力，进一步转化为开放手术的抗(再)狭窄应用。
At present, there are no clinical options for preventing neointima-caused (re)stenosis after open surgery such as bypass surgery for treating flow-limiting vascular disease. Perivascular drug delivery is a promising strategy, but in translational research, it remains a major challenge to achieve long-term (e.g., > 3 months) anti(re)stenotic efficacy. In this study, we engineered a unique drug delivery system consisting of durable unimolecular micelles, formed by single multiarm star amphiphilic block copolymers with only covalent bonds, and a thermosensitive hydrogel formed by a poly(lactide-co-glycolide)–poly(ethylene glycol)–poly(lactide-co-glycolide) triblock copolymer (abbreviated as triblock gel) that is stable for about 4 weeks in vitro. The drug-containing unimolecular micelles (UMs) suspended in Triblock gel were able to sustain rapamycin release for over 4 months. Remarkably, even 3 months after perivascular application of the rapamycin-loaded micelles in Triblock gel in the rat model, the intimal/medial area ratio (a restenosis measure) was still 80% inhibited compared to the control treated with empty micelle/gel (no drug). This could not be achieved by applying rapamycin in Triblock gel alone, which reduced the intimal/medial ratio only by 27%. In summary, we created a new UM/Triblock gel hybrid system for perivascular drug delivery, which produced a rare feat of 3-month restenosis inhibition in animal tests. This system exhibits a real potential for further translation into an anti(re)stenotic application with open surgery.
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影响因子：
14
作者：
Brinkman, Ashley M.;Chen, Guojun;Wang, Yidan;Hedman, Curtis J.;Sherer, Nathan M.;Havighurst, Thomas C.;Gong, Shaoqin;Xu, Wei
通讯作者：
Xu, Wei
影响因子：
14
作者：
Guo, Jintang;Hong, Hao;Chen, Guojun;Shi, Sixiang;Zheng, Qifeng;Zhang, Yin;Theuer, Charles P.;Barnhart, Todd E.;Cai, Weibo;Gong, Shaoqin
通讯作者：
Gong, Shaoqin
影响因子：
5.8
作者：
Antunes, Filipe E.;Gentile, Luigi;Ranieri, Giuseppe Antonio
通讯作者：
Ranieri, Giuseppe Antonio
DOI：
10.1152/ajpheart.00914.2013
发表时间：
2014-11-15
影响因子：
4.8
作者：
Gregory, Elaine K.;Webb, Antonio R.;Kibbe, Melina R.
通讯作者：
Kibbe, Melina R.
影响因子：
4.3
作者：
Jim, Jeffrey;Owens, Pamela L.;Rubin, Brian G.
通讯作者：
Rubin, Brian G.