Hyaluronic acid-based hydrogel for regional delivery of paclitaxel to intraperitoneal tumors.
Hyaluronic acid-based hydrogel for regional delivery of paclitaxel to intraperitoneal tumors.
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基于透明质酸的水凝胶，用于将紫杉醇局部递送至腹膜内肿瘤。
DOI：
10.1016/j.jconrel.2011.12.001
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发表时间：
2012-03-28
期刊：
影响因子：
--
通讯作者：
Yeo Y
中科院分区：
文献类型：
--
作者：
Bajaj G;Kim MR;Mohammed SI;Yeo Y
腹腔内化疗是治疗局限于腹腔的局部或区域性恶性肿瘤如卵巢癌的有效方法。然而，IP化疗的一个持续的主要挑战是需要在腹腔内提供有效的药物浓度，并维持较长时间。我们假设透明质酸（HA）基原位交联水凝胶可以作为紫杉醇（PTX）颗粒的载体，以提高其IP保留率和治疗效果。体外凝胶降解和释放动力学研究表明，透明质酸凝胶可以捕获微颗粒PTX （bbb100 μm）并在10天内释放药物，并逐渐被透明质酸酶降解，但对紫杉醇（一种14纳米胶束形式的PTX）的保留作用有限。当给荷瘤裸鼠注射IP时，PTX以PTX凝胶的形式保留在腹腔内的效果最好（微粒PTX包裹在HA凝胶中），而紫杉醇凝胶和其他紫杉醇基制剂在腹腔内的残留量在14天后可以忽略不计。尽管PTX的IP潴留增加，但PTX-凝胶并没有比紫杉醇基制剂进一步减少肿瘤负荷，可能是由于PTX的溶解有限。这一结果表明，药物的空间可用性不一定转化为增强的抗肿瘤作用，除非它伴随着时间可用性。
Intraperitoneal (IP) chemotherapy is an effective way of treating local and regional malignancies confined in the peritoneal cavity such as ovarian cancer. However, a persistent major challenge in IP chemotherapy is the need to provide effective drug concentrations in the peritoneal cavity for an extended period of time. We hypothesized that hyaluronic acid (HA)-based in-situ crosslinkable hydrogel would serve as a carrier of paclitaxel (PTX) particles to improve their IP retention and therapeutic effects. In-vitro gel degradation and release kinetics studies demonstrated that HA gels could entrap microparticulate PTX (>100 μm) and release the drug over 10 days, gradually degraded by hyaluronidase, but had limited effect on retention of Taxol, a 14-nm micelle form of PTX. When administered IP to tumor-bearing nude mice, PTX was best retained in the peritoneal cavity as PTX-gel (microparticulate PTX entrapped in the HA gel), whereas Taxol-gel and other Taxol-based formulations left negligible amount of PTX in the cavity after 14 days. Despite the increase in IP retention of PTX, PTX-gel did not further decrease the tumor burdens than Taxol-based formulations, presumably due to the limited dissolution of PTX. This result indicates that spatial availability of a drug does not necessarily translate to the enhanced anti-tumor effect unless it is accompanied by the temporal availability.
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影响因子：
158.5
作者：
Alberts, DS;Liu, PY;Hoskins, WJ
通讯作者：
Hoskins, WJ
影响因子：
3.8
作者：
HIRANO, K;HUNT, CA
通讯作者：
HUNT, CA
影响因子：
4.9
作者：
Kohane, DS;Tse, JY;Langer, R
通讯作者：
Langer, R
影响因子：
3
作者：
Lu, Hongxia;Li, Bin;Xu, Congjian
通讯作者：
Xu, Congjian
DOI：
10.3322/caac.20113
发表时间：
2011-05
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Jelovac D;Armstrong DK
通讯作者：
Armstrong DK