Target drug delivery system as a new scarring modulation after glaucoma filtration surgery.
Target drug delivery system as a new scarring modulation after glaucoma filtration surgery.
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DOI：
10.1186/1746-1596-6-64
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发表时间：
2011-07-08
影响因子：
2.6
通讯作者：
Ge J
中科院分区：
文献类型：
--
作者：
Shao T;Li X;Ge J
青光眼滤过手术后的过度伤口愈合是手术失败的主要决定因素，这是由人Tenon囊成纤维细胞（HTF）的激活引起的。为了缓解过度的伤口愈合，局部使用抗增殖剂，如丝裂霉素C（MMC）和5-氟尿嘧啶（5-FU），提高了手术成功率，但这些药物的传统给药可导致多种毒性和非特异性损伤。然而，调节伤口愈合过程以防止过度的成纤维细胞增殖和瘢痕形成可以在改善手术结果中发挥重要作用。因此，需要寻找替代的给药模式和新的药物，以减少眼部并发症，提高手术的成功率。我们已经表明，有一个术后过表达的LDL受体（LDLr）在激活的HTFs可能提供一个新的目标，药物输送系统。我们推测，抗纤维化药物（MMC）包裹在低密度脂蛋白靶向药物递送系统（LDL-MMC-壳聚糖纳米粒）可能被提议用于抗瘢痕治疗，以增加安全性和有效性，并减少毒性。合成了丝裂霉素C的壳聚糖基高分子前药，并证明其细胞毒性较低。此外，我们建议透明质酸膜作为容器，在青光眼滤过手术后的结膜下滤过部位逐渐释放LDL-MMC-壳聚糖纳米颗粒，以消除LDL-MMC-壳聚糖纳米颗粒。该策略可适用于结膜伤口过度愈合期间的抗疤痕治疗。这一假说综合了靶向给药和抗纤维化药物的优点，如高效、方便、低毒性。
Excessive wound healing following glaucoma filtration surgery is the main determinant of surgical failure, resulting from the activation of human Tenon's capsule fibroblasts (HTFs). To mitigate the excessive wound healing, the topicall use of antiproliferative agents, such as mitomycin C (MMC) and 5-fluorouracil (5-FU), has increased the surgery success rate, but the traditional administration of these agents can result in a variety of toxicities with nonspecific damage. However, modulation of the wound healing process to prevent excessive fibroblast proliferation and scar formation can play a major role in improving the outcome of surgery. Therefore, the search for alternative modes of drug delivery and new agents is needed to minimize the ocular complications and improve the success of surgery. We have shown that there is a postoperative overexpression of the LDL receptor (LDLr) in the activated HTFs may provide a novel target for drug delivery systems. We hypothesize that antifibrotic agents (MMC) encapsulated in LDLr targeting drug delivery system (LDL-MMC-chitosan nanoparticles) may be proposed in anti-scarring therapy to increase the safety and effectiveness and to reduce toxicity. A chitosan-based polymeric predrug of MMC was synthesized and its cytotoxicity was proved to be low. In addition, we propose hyaluronic acid film as a container to release LDL-MMC-chitosan nanoparticles gradually at subconjunctival filtering site after glaucoma filtration surgery to eliminate the LDL-MMC-chitosan nanoparticles. This strategy can be applicable to anti-scarring therapy during excessive conjunctival wound healing. This hypothesis integrates advantages of the targeting drug delivery and antifibrotic agents, such as high efficiency, convenience, and lower the toxicity.
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影响因子：
1.2
作者：
Adjadj, E.;Roy, S.;Drewe, J.
通讯作者：
Drewe, J.
影响因子：
3.5
作者：
Li, H;Marotta, DE;Zheng, G
通讯作者：
Zheng, G
影响因子：
4
作者：
Mansouri, Kaweh;Ravinet, Emilie
通讯作者：
Ravinet, Emilie
影响因子：
4.4
作者：
Memarzadeh, Farnaz;Varma, Rohit;Eliott, Dean
通讯作者：
Eliott, Dean
影响因子：
2.3
作者：
Shao, Tingting;Gao, Qianying;Ge, Jian
通讯作者：
Ge, Jian