Key Laboratory of Standardization of Chinese Herbal Medicine, Ministry of Education, State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Key Laboratory of Standardization of Chinese Herbal Medicine, Ministry of Education, State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Biomater Adv. 2022 May;136:212798. doi: 10.1016/j.bioadv.2022.212798. Epub 2022 Apr 12.
The blocking of gastric mucosal intestinal metaplasia (IM) has been considered to be the pivotal method to control the occurrence of gastric cancer. However, there is still a lack of effective therapeutic agent. Here, we developed mucus-penetrating liposome system by covering surface with polyethylene glycol (PEG) chains (hydrophilic and electroneutral mucus-inert material) to co-delivery candidate drugs combination. Then studied the impact on the transmucus performance of different conformations, which were constructed by controlling the density of PEG chains on the surface. The results showed that the particle size of 5%PEG-Lip was less than 120 nm, the polydispersity index was less than 0.3, and the surface potential tended to be neutral. The D value (long chain spacing) of 5% PEG-Lip was 3.25 nm, which was close to the R value (diameter of spherical PEG long chain group without external force interference) of 3.44 nm, and the L value (extended length) was slightly larger than 3.44 nm. In this case, PEG showed mushroom-brush transitional conformation on the surface of liposomes. This conformation was not only promoted stable delivery, but also shielded the capture of mucus more favorably, leading to a more unrestricted transportation in mucus. The further in vivo experimental results demonstrated the rapid distribution of liposomes, which gradually appeared both in the superficial and deep glandular of mucosa and gland cells at 1 h and absorbed into the cell cytoplasm at 6 h. The 5% PEG-Lip with the mushroom-brush transitional configuration recalled abnormal organ index and improved inflammation and intestinal metaplasia. The modified PEG conformation assay presented here was more suitable for liposomes. This PEG-modified liposome system has potential of mucus-penetrating and provides a strategy for local treatment of gastric mucosal intestinal metaplasia.
阻断胃黏膜肠上皮化生（IM）被认为是控制胃癌发生的关键方法。然而，仍然缺乏有效的治疗药物。在这里，我们通过覆盖表面的聚乙二醇（PEG）链（亲水性和电中性的黏液惰性材料）来开发透黏液脂质体系统，以共同递送候选药物组合。然后研究了不同构象对跨黏液性能的影响，这些构象是通过控制表面上 PEG 链的密度来构建的。结果表明，5%PEG-Lip 的粒径小于 120nm，多分散指数小于 0.3，表面电位趋于中性。5%PEG-Lip 的 D 值（长链间距）为 3.25nm，接近 3.44nm 的 R 值（无外力干扰时球形 PEG 长链基团的直径），L 值（延伸长度）略大于 3.44nm。在这种情况下，PEG 在脂质体表面呈现出蘑菇刷过渡构象。这种构象不仅促进了稳定的递药，而且更有利于屏蔽黏液的捕获，从而在黏液中更不受限制地运输。进一步的体内实验结果表明，脂质体迅速分布，在 1h 时逐渐出现在黏膜的浅层和深层腺体以及腺细胞中，并在 6h 时被吸收到细胞质中。具有蘑菇刷过渡构象的 5%PEG-Lip 可恢复异常器官指数，并改善炎症和肠上皮化生。本文提出的修饰 PEG 构象的测定方法更适合脂质体。这种经 PEG 修饰的脂质体系统具有穿透黏液的潜力，为胃黏膜肠上皮化生的局部治疗提供了一种策略。
