a Department of Pharmaceutical Sciences, College of Pharmacy & Allied Health Professions , South Dakota State University , Brookings , USA.
b Department of Pharmaceutics , National Institute of Pharmaceutical Education and Research (NIPER) , Mohali , India.
Expert Opin Drug Deliv. 2018 Nov;15(11):1127-1142. doi: 10.1080/17425247.2018.1537261. Epub 2018 Oct 25.
A major concern that limits the success of cancer chemotherapy is multidrug resistance (MDR). The drug resistance mechanisms are either host related or tumor related. The host tumor interacting factors also contribute to MDR. Multifunctional polymeric micelles offer several advantages in circumventing MDR due to their design, selectivity, and stability in cancer microenvironment.
The review is broadly divided into two parts: the first part covers MDR and its mechanisms; the second part covers multifunctional polymeric micelles in combating MDR through its state-of-the-art design. This part covers various strategies like use of P-gp transporter inhibitors, TPGS, pH & thermo-sensitive, and siRNA for selectivity of PMs against multidrug-resistant tumors.
Numerous approaches have been tested using polymeric micelles to overcome MDR tumors. However, these are either limited to only in-vitro investigations and/or preliminary preclinical models and do not investigate the underlying biological mechanism. Hence, there exists an unmet need to perform fundamental research that focuses on studying the underlying mechanism and preclinical/clinical testing of the micellar formulations.
限制癌症化疗成功的一个主要问题是多药耐药（MDR）。耐药机制要么与宿主有关，要么与肿瘤有关。宿主-肿瘤相互作用因素也促成了多药耐药。多功能聚合物胶束由于其设计、选择性和在癌症微环境中的稳定性，在克服 MDR 方面具有多种优势。
综述大致分为两部分：第一部分涵盖 MDR 及其机制；第二部分涵盖多功能聚合物胶束通过其最先进的设计在对抗 MDR 方面的应用。这部分涵盖了各种策略，如使用 P-糖蛋白转运体抑制剂、TPGS、pH 和温度敏感以及 siRNA 来提高 PM 对多药耐药肿瘤的选择性。
已经使用聚合物胶束测试了许多方法来克服 MDR 肿瘤。然而，这些方法要么仅限于体外研究和/或初步的临床前模型，要么没有研究潜在的生物学机制。因此，需要进行基础研究，重点研究胶束制剂的潜在机制和临床前/临床测试。
