College of Pharmacy, Liaoning University, Liaoning, Shenyang, 110036, China.
State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.
J Nanosci Nanotechnol. 2019 Apr 1;19(4):2260-2268. doi: 10.1166/jnn.2019.16531.
With the increasing development in scientific technology, building a nanocarrier system for cancer drugs has become a bliss for cancer patients. To allow for the oral administration of hydrophilic drugs, a nanocarrier that was based on negatively charged graphene oxide (GO) and prepared through the Layer-by-Layer (LbL) self-assembly of poly(acrylic acid)-cysteine (PAA-cys) and poly(allylamine hydrochloride) (PAH) was established. In the present study, we demonstrated the excellent biological properties of GO, the biological adhesiveness of PAA-cys, and the protection and controlled release profiles of polyelectrolyte. Pingyangmycin (PYM) was loaded onto the nanocarrier through non-covalent interactions. drug release studies of the prepared PAA-cys-PAH-GO-PYM were pH-sensitive and showed sustained release effects for over 8 h, before they were completely expelled by gastrointestinal peristalsis. Furthermore, cell viability experiments using A549 lung adenocarcinoma cells revealed that the IC50 of PAA-cys-PAH-GO-PYM, free drug, and GO-PYM were 159.241 M, 134.960 M, and 129.815 M respectively, indicating the higher retention and cytotoxicity of PYM When comparing the oral bioavailability of PYM with free drug, pharmacokinetics studies showed a 1.03-fold and 1.74-fold increase after GO loading and double-layer polyelectrolyte coating, respectively. Thus, PAA-cys-PAH-GO was successfully developed for oral delivery of PYM as anti-cancer therapy, and may provide further insight for oral administration of GO-based nanomaterials.
随着科学技术的不断发展，为癌症药物构建纳米载体系统已成为癌症患者的福音。为了实现亲水性药物的口服给药，我们构建了一种基于带负电荷的氧化石墨烯（GO）的纳米载体，该载体是通过聚（丙烯酸）-半胱氨酸（PAA-cys）和聚（烯丙基胺盐酸盐）（PAH）的层层（LbL）自组装制备的。在本研究中，我们展示了 GO 的优异生物特性、PAA-cys 的生物黏附性以及聚电解质的保护和控制释放特性。平阳霉素（PYM）通过非共价相互作用装载到纳米载体上。所制备的 PAA-cys-PAH-GO-PYM 的药物释放研究表明，其具有 pH 敏感性，并表现出超过 8 小时的持续释放效果，随后被胃肠道蠕动完全排出。此外，使用 A549 肺腺癌细胞进行细胞活力实验表明，PAA-cys-PAH-GO-PYM、游离药物和 GO-PYM 的 IC50 分别为 159.241 μM、134.960 μM 和 129.815 μM，表明 PYM 的保留率和细胞毒性更高。与游离药物相比，GO 负载和双层聚电解质包被后，PYM 的口服生物利用度分别提高了 1.03 倍和 1.74 倍。因此，成功开发了 PAA-cys-PAH-GO 用于 PYM 的口服递送作为抗癌治疗，并可能为基于 GO 的纳米材料的口服给药提供进一步的见解。
