Paclitaxel gelatin nanoparticles for intravesical bladder cancer therapy.
Paclitaxel gelatin nanoparticles for intravesical bladder cancer therapy.
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DOI：
10.1016/j.juro.2010.11.091
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发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Au JL
中科院分区：
文献类型：
--
作者：
Lu Z;Yeh TK;Wang J;Chen L;Lyness G;Xin Y;Wientjes MG;Bergdall V;Couto G;Alvarez-Berger F;Kosarek CE;Au JL
我们已经证明，向肿瘤细胞的药物递送不足是非肌肉侵袭性膀胱癌膀胱内治疗失败的主要原因。这部分是由于治疗期间尿液产生稀释了药物浓度。为了解决这个问题，我们开发了紫杉醇 (PNP) 明胶纳米颗粒，旨在产生恒定的药物浓度。在狗身上评估了尿液、膀胱组织和肿瘤中可以达到恒定的治疗浓度的假设。我们研究了 PNP 在体外培养基中的药物释放。在无肿瘤狗和患有自然发生的移行细胞癌的宠物狗中进行了体内研究，确定了 PNP 的药代动力学（血浆、尿液和肿瘤）。 PNP 在体外和体内的紫杉醇释放速率受到水介质中药物溶解度的限制。这一特性产生了恒定的药物浓度，与 2 小时治疗期间尿量的变化无关。膀胱内 PNP 显示出较低的全身吸收和良好的膀胱组织/肿瘤靶向和保留特性，药理活性浓度在肿瘤中保留至少 1 周。 PNP 的持续药物释放可以克服新产生的尿液稀释药物的问题，并且肿瘤中持续的药物水平可以减少治疗频率。
We have shown that inadequate drug delivery to tumor cells is a major cause of failures in intravesical therapy of nonmuscle-invading bladder cancer. This is partly due to the dilution of drug concentration by urine production during treatment. To address this problem, we developed gelatin nanoparticles of paclitaxel (PNP) designed to yield constant drug concentrations. The hypothesis that constant, therapeutic concentrations in urine, bladder tissue and tumors can be attained was evaluated in dogs. We studied the drug release from PNP in culture medium in vitro. In vivo studies were performed in tumor-free dogs and in pet dogs with naturally occurring transitional cell carcinoma, where the pharmacokinetics (plasma, urine and tumors) of PNP was determined. The release of paclitaxel from PNP in vitro and in vivo was rate-limited by the drug solubility in aqueous medium. This property yielded constant drug concentrations independent of changes in the urine volume over the 2-hr treatment. Intravesical PNP showed low systemic absorption and favorable bladder tissue/tumor targeting and retention properties, with pharmacologically active concentrations retained in tumors for at least 1 week. The constant drug release from PNP may overcome the problem of drug dilution by newly produced urine and the sustained drug levels in tumors may reduce the treatment frequency.
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影响因子：
11.5
作者：
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通讯作者：
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