In this work, a series of poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) diblock copolymers with relatively short PLGA blocks were synthesized by ring-opening polymerization of D,L-lactide and glycolide in the presence of monomethoxy PEG with Mn of 2000. Spherical micelles were obtained by self-assembly of copolymers using direct dissolution method. The degradation of the micelles was investigated under in vitro conditions at 37 °C. The effects of chemical composition on micelle degradation were evaluated from NMR, GPC, DLS and TEM measurements. The molar mass of copolymers constantly decreases during degradation in all cases. The copolymers with longer hydrophobic PLGA blocks exhibit larger molar mass decrease rate since only the PLGA block is degradable. Meanwhile, the molar mass distribution remains almost unchanged, in agreement with random chain cleavage. NMR spectra show that the final degradation products are lactic acid and glycolic acid. A pH decrease is also detected during degradation. The size of the micelle depends on the chemical composition of copolymers. Micelle size is smaller for copolymers with longer hydrophobic PLGA blocks because of more compact core structure. With the hydrolysis of the PLGA blocks, the structure of micelles becomes looser, and the micelle size exhibits a sharp increase after a lag time. At the later stage of degradation, the size of micelles decreases as they become unstable and could collapse. The micelle structure could be clearly distinguished after 45 days degradation for copolymers with longer PLGA blocks, whereas those with shorter PLGA blocks lost the structural integrity. It is also noteworthy that the LA/GA ratio has little effect on the degradation of PLGA-PEG copolymer micelles, which may be related to the amorphous structure of PLGA block and the relatively short block length. These findings should be helpful for the conception of drug delivery systems based on PLGA-PEG micelles.

在这项工作中，通过D，L-丙交酯的开环聚合反应合成了一系列具有相对较短PLGA嵌段的聚（D，L-丙交酯-共-乙交酯）-聚（乙二醇）（PLGA-PEG）二嵌段共聚物在Mn为2000的单甲氧基PEG存在下，制备乙交酯和乙交酯。采用直接溶解法，通过共聚物的自组装获得球形胶束。在体外研究胶束的降解条件在37°C。通过NMR，GPC，DLS和TEM测量评估化学组成对胶束降解的影响。在所有情况下，共聚物的摩尔质量在降解过程中均不断降低。具有较长疏水性PLGA嵌段的共聚物表现出较大的摩尔质量降低速率，因为仅PLGA嵌段是可降解的。同时，摩尔质量分布几乎保持不变，这与无规链断裂一致。NMR光谱表明最终的降解产物是乳酸和乙醇酸。在降解过程中还会检测到pH降低。胶束的大小取决于共聚物的化学组成。对于具有较长疏水性PLGA嵌段的共聚物，胶束尺寸较小，因为其芯结构更紧凑。随着PLGA嵌段的水解，胶束的结构变得更松散，并且胶束大小在滞后时间后急剧增加。在降解的后期，胶束的尺寸会随着它们变得不稳定并可能塌陷而减小。具有较长PLGA嵌段的共聚物在降解45天后可以清楚地区分胶束结构，而具有较短PLGA嵌段的共聚物则失去了结构完整性。还值得注意的是，LA / GA比对PLGA-PEG共聚物胶束的降解影响很小，这可能与PLGA嵌段的无定形结构和较短的嵌段长度有关。这些发现应有助于基于PLGA-PEG胶束的药物递送系统的概念。胶束的尺寸随着它们变得不稳定并可能塌陷而减小。具有较长PLGA嵌段的共聚物在降解45天后可以清楚地区分胶束结构，而具有较短PLGA嵌段的共聚物则失去了结构完整性。还值得注意的是，LA / GA比对PLGA-PEG共聚物胶束的降解影响很小，这可能与PLGA嵌段的无定形结构和较短的嵌段长度有关。这些发现应有助于基于PLGA-PEG胶束的药物递送系统的概念。胶束的尺寸会随着它们变得不稳定并可能塌陷而减小。具有较长PLGA嵌段的共聚物在降解45天后可以清楚地区分胶束结构，而具有较短PLGA嵌段的共聚物则失去了结构完整性。还值得注意的是，LA / GA比对PLGA-PEG共聚物胶束的降解影响很小，这可能与PLGA嵌段的无定形结构和较短的嵌段长度有关。这些发现应有助于基于PLGA-PEG胶束的药物递送系统的概念。还值得注意的是，LA / GA比对PLGA-PEG共聚物胶束的降解影响很小，这可能与PLGA嵌段的无定形结构和较短的嵌段长度有关。这些发现应有助于基于PLGA-PEG胶束的药物递送系统的概念。还值得注意的是，LA / GA比对PLGA-PEG共聚物胶束的降解影响很小，这可能与PLGA嵌段的无定形结构和较短的嵌段长度有关。这些发现应有助于基于PLGA-PEG胶束的药物递送系统的概念。