College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.
School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Colloids Surf B Biointerfaces. 2020 May;189:110832. doi: 10.1016/j.colsurfb.2020.110832. Epub 2020 Jan 30.
Bladder cancer, with the highest recurrence rate in all malignancy, is a common urologic cancer that arises on the bladder mucosa. Currently, tumor resection followed by intravesical chemotherapy is the primary treatment of bladder cancer, which has limited effectiveness ascribe to short dwell-time of intravesical drugs in bladder. Therefore, there is a need to develop mucoadhesive and sustained drug delivery systems to increase drug residence time for intravesical chemotherapy. In this study, poly(amidoamine) (PAMAM) dendrimers were modified onto the surface of mesoporous silica nanoparticles (MSNPs) through a layer-by-layer grafting method. A series of PAMAM-modified MSNPs were prepared and compared for their mucoadhesive capabilities on pig bladder wall and controlled drug release properties. Results demonstrated an increase in the mucoadhesive capacity of PAMAM-modified MSNPs upon an increase in the number of PAMAM amino groups, and the maximum nanoparticle mucoadhesivity was observed after two-generation PAMAM were grafted on the surface of MSNPs. An antineoplastic, doxorubicin, was encapsulated in the mesopores of PAMAM-modified MSNPs, and the drug-loaded nanoparticles can provide a sustained drug release triggered by acidic pH. The present study demonstrates that the mucoadhesive and drug release properties of MSNPs can be controlled by the layer number of PAMAM dendrimers on the nanoparticle surface, holding significant potential for the development of mucoadhesive drug delivery systems for bladder cancer therapy.
膀胱癌是所有恶性肿瘤中复发率最高的一种，是一种常见的泌尿系统癌症，起源于膀胱黏膜。目前，肿瘤切除后进行膀胱内化疗是膀胱癌的主要治疗方法，但由于膀胱内药物在膀胱中的停留时间短，其效果有限。因此，需要开发具有黏膜黏附性和持续药物释放系统的药物，以增加膀胱内化疗的药物停留时间。在本研究中，通过层层嫁接的方法将聚（酰胺-胺）（PAMAM）树枝状大分子修饰到介孔硅纳米粒子（MSNPs）的表面。制备了一系列 PAMAM 修饰的 MSNPs，并比较了它们在猪膀胱壁上的黏膜黏附能力和控制药物释放性能。结果表明，随着 PAMAM 氨基数量的增加，PAMAM 修饰的 MSNPs 的黏膜黏附能力增加，在将第二代 PAMAM 接枝到 MSNPs 表面后，观察到纳米颗粒的最大黏膜黏附性。阿霉素是一种抗肿瘤药物，被包裹在 PAMAM 修饰的 MSNPs 的介孔中，载药纳米颗粒可以在酸性 pH 值触发下提供持续的药物释放。本研究表明，MSNPs 的黏膜黏附性和药物释放性能可以通过纳米颗粒表面的 PAMAM 树状大分子的层数来控制，这为开发用于膀胱癌治疗的黏膜黏附性药物传递系统具有重要意义。
