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

五肽重复序列的高分子聚合物（VPGVG）n简称Vpp，是磷酸化和氧化还原型控释装置的基础。Vpp经历称为凝聚的自组装，其中形成直径在400至600 nm范围内的凝聚液滴。通过钴-60 γ-辐射凝聚液滴交联的纳米颗粒可用作药物释放装置。合成了Vpp和无规共聚物[8（VPGVG），2（VPGK（Z）G）]简单VK（Z）pp和[8（VPGVG），2（VPGK（Boc）G）]简单VK（Boc）pp，其中VPGVG与VPGK（Z）G或VPG（Boc）G的摩尔比为8：2。在55- 60 ℃下处于凝聚状态的这些聚合物和共聚物的凝聚液滴通过钴-60 γ-辐射交联以产生在200 - 400 nm范围内的纳米颗粒。所得纳米粒子在酶处理中稳定。抗肿瘤药物阿霉素在Vpp和VK（Boc）pp纳米粒中的载药量分别为80%和77%。阿霉素从VPP衍生的和VK（Boc）pp衍生的纳米颗粒的释放分别为13天和19天（释放一半量的负载药物的时间）。接下来，我们合成了两种无规共聚物，[30（VPGVG），（RGYSL）]和[7（VPGVG），3（VPGK（NMeN）G）]，其中添加了RGYSL（其是用于通过蛋白激酶磷酸化的肽底物）和VPGK（NMeN）G（其是具有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高温移动，通过去磷酸化向低温移动。此外，[7（VPGVG），3（VPGK（NMeN）G）]的自组装起始温度通过氧化向高温移动，通过还原向低温移动。[30（VPGVG），（RGYSL）]和[7（VPGVG），3（VPGK（NMeN）G）]纳米粒药物控释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.