Polylysine and cysteine functionalized chitosan nanoparticle as an efficient platform for oral delivery of paclitaxel
Polylysine and cysteine functionalized chitosan nanoparticle as an efficient platform for oral delivery of paclitaxel
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DOI：
10.1016/j.carbpol.2019.115484
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发表时间：
2020-02-01
影响因子：
11.2
通讯作者：
Li, Juan
中科院分区：
文献类型：
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作者：
Du, Xiao;Yin, Shaoping;Li, Juan
使用阳离子聚赖氨酸（PL）聚合物和L-半胱氨酸开发并研究了一种新型基于壳聚糖的多功能纳米颗粒（PY-CS-PLA），用于紫杉醇（PTX）的口服给药。作为两亲性聚合物，PY-CS-PLA具有良好的自组装能力，形成平均尺寸为165 nm的球形纳米粒子，并将PTX封装到疏水核中。观察到封装的PTX从功能化壳聚糖纳米颗粒中持续释放，并且与介质的pH值在1.2至7.4范围内呈正相关。体外研究表明PY-CS-PLA/PTX可以有效增强Caco-2细胞对PTX的摄取。药代动力学结果表明，PY-CS-PLA/PTX在大鼠体内的口服生物利用度是紫杉醇的5.63倍。此外，PY-CS-PLA/PTX改善了PTX在肿瘤部位的分布，在Heps荷瘤小鼠中表现出更好的抗肿瘤功效，并且比其他制剂的毒性更小。总之，PY-CS-PLA/PTX纳米颗粒可能被开发为一种有前景的递送载体，用于提高疏水性抗肿瘤药物的口服生物利用度和治疗效果。
A novel chitosan-based multifunctional nanoparticle (PY-CS-PLA) using cationic polylysine (PL) polymer and L-cysteine has been developed and investigated for the oral delivery of paclitaxel (PTX). As amphiphilic polymer, PY-CS-PLA presented good capability in self-assembling into spherical nanoparticle with mean size of 165 nm, and encapsulating PTX into the hydrophobic core. The encapsulated PTX was observed to be sustainedly released from the functionalized chitosan nanoparticle, and with a positive correlation to the pH value of the medium in the range of 1.2 to 7.4. The in vitro studies indicated that PY-CS-PLA/PTX could effectively enhance the cellular uptake of the PTX in Caco-2 cells. Pharmacokinetic result indicated that the oral bioavailability of PY-CS-PLA/PTX in rats was determined to be 5.63-fold to that of Taxol. Moreover, PY-CS-PLA/PTX improved the distribution of PTX in tumor site and presented better antitumor efficacy in Heps tumor-bearing mice and with less toxicity than other formulations. In conclusion, the PY-CS-PLA/PTX nanoparticle might be developed as a promising delivery vehicle for improving the oral bioavailability and therapeutic effect of hydrophobic antitumor drugs.