Study on Design of Biodegradable Nanoparticles with Function of Controlled Drug Release

重复五肽序列的高分子（VPGVG），简称Vpp，是磷酸化和氧化还原控制释放装置的基础。Vpp会发生自组装，称为凝聚，形成直径在400 - 600nm之间的凝聚液滴。用钴-60 γ-辐照凝聚液滴交联制备的纳米颗粒可作为药物释放装置。合成了Vpp和随机共聚物[8(VPGVG), 2(VPGK(Z)G)]简式VK(Z)pp和[8(VPGVG), 2(VPGK(Boc)G)]简式VK(Boc)pp，其中VPGVG与VPGK(Z)G或VPG(Boc)G的摩尔比为8比2。在55 ~ 60℃的温度下，聚合物和共聚物的聚簇液滴在钴-60 γ辐射下交联，得到了200 ~ 400 nm的纳米颗粒。所制备的纳米颗粒在酶的作用下是稳定的。抗肿瘤药物阿霉素在vpp衍生纳米颗粒和VK(Boc)pp衍生纳米颗粒中的负载率分别为80%和77%。vpp衍生纳米颗粒和VK(Boc)pp衍生纳米颗粒的阿霉素释放时间分别为13天和19天（释放药量的一半时间）。接下来，我们合成了两种随机共聚物，[30(VPGVG), (RGYSL)]和[7(V PGVG), 3 (VPGK(NMeN)G)]，其中RGYSL是蛋白激酶磷酸化的肽底物，VPGK(NMeN)G是带n -甲基烟酰胺的氧化还原肽。[30(VPGVG), (RGYSL)]的自组装起始温度通过磷酸化向较高温度转移，通过去磷酸化向较低温度转移。此外，[7(VPGVG), 3(VPGK(NMeN)G)]的自组装起始温度通过氧化向高温转移，通过还原向低温转移。[30(VPGVG), (RGYSL)]和[7(VPGVG), 3(VPGK(NMeN)G)]纳米颗粒控释药物的进一步研究正在进行中。

The high polymer of repeating pentapeptide sequence, (VPGVG)n simply Vpp, is basis for phosphorylation-responsible and redox-responsible controlled release devices. Vpp undergoes self-assembly called coacervation, where coacervate droplets with diameter in the range of 400 to 600 nm are formed. The nanoparticles cross-linked by cobalt-60 γ-irradiation of coacervate droplets are useful as drug release devices. Vpp and random copolymers, [8(VPGVG), 2(VPGK(Z)G)] simply VK(Z)pp and [8(VPGVG), 2(VPGK(Boc)G)] simply VK(Boc)pp, where the molar ratio of VPGVG to VPGK(Z)G or VPG(Boc)G is 8 to 2 were synthesized. The coacervate droplets of these polymer and copolymers in the coacervate state at 55-60'C were cross-linked by cobalt-60 γ-irradiation to yield nanoparticles in the range of 200 to 400 nm. The nanoparticles obtained were stable in the treatment of enzyme. The loading antitumor drug, adriamycin, into Vpp-derived and VK(Boc)pp-derived nanoparticles were 80 and 77%, respectively. The release of adriamycin from Vpp-derived and VK(Boc)pp-derived nanoparticles were 13 and 19 days (time for releasing half amount of loaded drug), respectively. Next we synthesized two random copolymers, [30(VPGVG), (RGYSL)] and [7(V PGV G), 3 (VPGK(NMeN)G)], where RGYSL which is a peptide substrate for phosphorylation by protein kinase and VPGK(NMeN)G which is a redox peptide with N-methylnicotinamide were added. The onset temperature of self-assembly of [30(VPGVG), (RGYSL)] shifted to higher temperature by phosphorylation and to lower temperature by dephosphorylation. Moreover, the onset temperature of self-assembly of [7(VPGVG), 3(VPGK(NMeN)G)] shifted to higher temperature by oxidation and to lower temperature by reduction. Further study on controlled drug release from nanoparticles of [30(VPGVG), (RGYSL)] and [7(VPGVG), 3(VPGK(NMeN)G)] is underway.