a Department of Pharmacy , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , Zhejiang Province , People's Republic of China.
b Department of Cell Biology and Biochemistry , Texas Tech University Health Sciences Center , Lubbock , TX , USA.
Expert Opin Drug Deliv. 2018 Sep;15(9):869-879. doi: 10.1080/17425247.2018.1517749. Epub 2018 Sep 10.
P-glycoprotein 1 (P-gp) pumps out many foreign/toxic substances out of the cells, including intracellular drugs, causing multidrug resistance (MDR) and chemotherapy failure. It remains quite a challenge to inhibit P-gp to combat MDR and improve cellular bioavailability since it requires efficient inhibitors along with adequate formulation strategy. Lately, nanocarriers are gaining much attention and form an attractive platform for delivering drugs into cells. Therefore, nanomaterials act as direct inhibitors of P-gp will be an attractive alternative to overcome MDR.
This paper reviews the most recent advances on those nanomaterials that are currently in the developmental stage and has proven useful to treat P-gp involved MDR. Also, we emphasize those emerging multifunctional nanomaterials that can construct 'smart' carriers for both tumor targeting and P-gp inhibition. Furthermore, the mechanisms behind P-gp inhibition and the nanoformulation strategies for drug delivery are also discussed.
In light of these updated reports, this review here seeks to suggest an alternative for the chemoresistant cases, and also bring about new thoughts on tackling P-gp concerned drug delivery issues. New advances in nanomaterials with P-gp inhibition are expected to broaden nanopharmaceutics and traditional chemotherapy applications in the coming years.
P-糖蛋白 1(P-gp)将许多外来/有毒物质从细胞内泵出,包括细胞内药物,导致多药耐药(MDR)和化疗失败。由于需要高效的抑制剂和适当的制剂策略,抑制 P-gp 以对抗 MDR 和提高细胞生物利用度仍然是一个挑战。最近,纳米载体受到了广泛关注,成为将药物递送到细胞内的有吸引力的平台。因此,纳米材料作为 P-gp 的直接抑制剂将是克服 MDR 的一种有吸引力的替代方法。
本文综述了目前处于开发阶段的、已被证明可用于治疗 P-gp 参与的 MDR 的最新型纳米材料的最新进展。此外,我们还强调了那些新兴的多功能纳米材料,它们可以构建用于肿瘤靶向和 P-gp 抑制的“智能”载体。此外,还讨论了 P-gp 抑制的机制以及用于药物递送的纳米制剂策略。
鉴于这些最新报告,本综述旨在为耐药病例提供一种替代方法,并为解决与 P-gp 相关的药物递送问题带来新的思路。具有 P-gp 抑制作用的纳米材料的新进展有望在未来几年拓宽纳米药物学和传统化疗的应用。