Nanoparticulate delivery of agents for induced elastogenesis in three-dimensional collagenous matrices.
Nanoparticulate delivery of agents for induced elastogenesis in three-dimensional collagenous matrices.
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DOI：
10.1002/term.1889
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发表时间：
2016-12
影响因子：
3.3
通讯作者：
Ramamurthi, Anand
中科院分区：
文献类型：
--
作者：
Venkataraman, Lavanya;Sivaraman, Balakrishnan;Vaidya, Pratik;Ramamurthi, Anand
关键词：
肾下主动脉壁弹性基质的降解是腹主动脉瘤（AAA）形成和进展的关键参数。它是由基质金属蛋白酶（MMP）-2和-9的慢性过度表达介导的，导致进行性弹性丧失和主动脉壁弱化。递送治疗剂以抑制MMP，同时诱导弹性基质的基于细胞的再生修复代表了减缓或阻止AAA生长的潜在策略。我们先前的研究已经证明，在二维（2-D）培养中，外源性递送弹性生成因子（如TGF-β1）以及MMP抑制剂（如强力霉素（DOX））后，健康和平滑肌瘤主动脉平滑肌细胞（SMC）的弹性生成诱导和MMP抑制。基于这些发现，以及其他证明在2-D培养中纳米颗粒递送这些药物的弹性益处的发现，我们开发了聚（丙交酯-共-乙交酯）纳米颗粒，用于在I型胶原凝胶的三维（3-D）凝胶内将DOX和TGF-β1局部、受控和持续地递送至人主动脉SMC（HASMC），其紧密地唤起动脉组织微环境。从这些NP释放的DOX和TGF-β1在21天的培养中积极影响胶原构建体内的弹性生成结果，这与培养基内外源性补充DOX和TGF-β1诱导的结果相当。然而，这是在比外源剂量的试剂低20倍的剂量下实现的，这说明它们从嵌入3-D支架内的NP的局部、受控和持续递送是定向弹性细胞生成的有效策略。
The degradation of elastic matrix in the infrarenal aortic wall is a critical parameter underlying the formation and progression of abdominal aortic aneurysms (AAAs). It is mediated by the chronic overexpression of matrix metalloproteases (MMPs) -2 and -9, leading to a progressive loss of elasticity and weakening of the aortic wall. Delivery of therapeutic agents to inhibit MMPs, while concurrently coaxing cell-based regenerative repair of the elastic matrix represents a potential strategy for slowing or arresting AAA growth. Our prior studies have demonstrated elastogenic induction of healthy and aneurysmal aortic smooth muscle cells (SMCs) and inhibition of MMPs, following exogenous delivery of elastogenic factors such as TGF-β1, as well as MMP-inhibitors such as doxycycline (DOX) in two-dimensional (2-D) culture. Based on these findings, and others that demonstrated elastogenic benefits of nanoparticulate delivery of these agents in 2-D culture, we have developed poly(lactide-co-glycolide) nanoparticles for localized, controlled and sustained delivery of DOX and TGF-β1 to human aortic SMCs (HASMCs) within a three-dimensional (3-D) gels of type-I collagen gel, which closely evoke the arterial tissue microenvironment. DOX and TGF-β1 released from these NPs influenced elastogenic outcomes positively within the collagen constructs over 21 days of culture, which were comparable to that induced by exogenous supplementation of DOX and TGF-β1 within the culture medium. However, this was accomplished at doses ∼20-fold lower than the exogenous dosages of the agents, illustrating that their localized, controlled, and sustained delivery from NPs embedded within a 3-D scaffold is an efficient strategy for directed elastogenesis.
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DOI：
10.1002/9780470514771.ch5
发表时间：
2007-01-01
期刊：
CULTURAL DIPLOMACY IN U.S.-JAPANESE RELATIONS, 1919-1941
影响因子：
--
作者：
Davidann, Jon Thares
通讯作者：
Davidann, Jon Thares
影响因子：
64.5
作者：
BATTEGAY, EJ;RAINES, EW;ROSS, R
通讯作者：
ROSS, R
影响因子：
7.6
作者：
DAVIES, AK;CUNDALL, RB;SLIFKIN, MA
通讯作者：
SLIFKIN, MA
影响因子：
5.8
作者：
Daugherty, Alan;Cassis, Lisa A
通讯作者：
Cassis, Lisa A
影响因子：
4.3
作者：
Curci, JA;Mao, DL;Thompson, RW
通讯作者：
Thompson, RW