壳聚糖酶解物和聚乙二醇-聚谷氨酸共聚物的立体稳定聚离子复合纳米凝胶用于递送伊立替康活性代谢物（SN-38）。
Sterically Stabilized Polyionic Complex Nanogels of Chitosan Lysate and PEG-b-Polyglutamic Acid Copolymer for the Delivery of Irinotecan Active Metabolite (SN-38).
机构信息
Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz 71345, Iran.
出版信息
Curr Drug Deliv. 2021;18(6):741-752. doi: 10.2174/1567201817999201103195846.
BACKGROUND
Poly Ionic Complex (PIC) nanogels are promising delivery systems with numerous attractions such as simple, fast, and organic solvent-free particle formation and mild drug loading conditions. Among polyelectrolytes, poly (L-amino acid) copolymers, such as poly (ethylene glycol)-block-poly (L-glutamic acid) copolymers (PEG-b-PGlu) are interesting biocompatible and biodegradable candidates bearing carboxylic acid functional groups.
OBJECTIVE
Aiming to solubilize and to preserve short-acting irinotecan active metabolite (SN38), sterically stabilized PIC nanogels were prepared through electrostatic charge neutralization between PEG-b-PGlu and chitosan lysate, a polycationic natural polymer obtained through digestion of chitosan by hydrogen peroxide oxidation and is soluble in a wide range of pH.
METHODS
Synthesis of PEG-b-PGlu was accomplished by N-carboxy anhydride polymerization of γ -benzyl L-glutamic acid, which is initiated by methoxy PEG-NH2 and successive debenzylation reaction.
RESULTS
The resulting block copolymer was characterized by FTIR, H-NMR, and Size Exclusion Chromatography (SEC). Self-assembling properties of the PIC nanogels were investigated by pyrene assay, Dynamic Light Scattering (DLS), and Transmission Electron Microscopy (TEM), indicating the formation of homogeneous spherical particles with a mean size of 28 nm at the PEGb- PGlu concentrations/LMWC weight ratio of 5:1. Upon direct loading of SN38, the drug solubility enhanced more than 4×10 folds with a mean loading efficiency of 89% and the drug loading of 30%. PIC nanogels exhibited zeta potential of +1 mV, acceptable biocompatibility, and superior cytotoxicity in murine colorectal carcinoma (CT26 cell line) compared to free drug.
CONCLUSION
In addition, the PIC nanogels provided SN38 protection against hydrolytic degradation in physiologic conditions. Conclusively, the well-tuned PIC nanogels are suggested as a potentially biocompatible nanocarrier for SN38 delivery.
背景
聚离子复合物（PIC）纳米胶是一种很有前途的药物传递系统，具有许多优点，如简单、快速、无有机溶剂的颗粒形成和温和的药物加载条件。在聚电解质中，聚（L-氨基酸）共聚物，如聚乙二醇-嵌段-聚（L-谷氨酸）共聚物（PEG-b-PGlu）是一种有趣的生物相容和可生物降解的候选物，带有羧酸官能团。
目的
为了增溶和保存短半衰期伊立替康活性代谢物（SN38），通过静电中和作用制备了具有空间稳定性的 PIC 纳米胶，PEG-b-PGlu 与壳聚糖水解物（一种通过过氧化氢氧化消化壳聚糖得到的多阳离子天然聚合物，在很宽的 pH 值范围内都可溶解）之间的静电中和作用。
方法
PEG-b-PGlu 的合成是通过 γ-苄基 L-谷氨酸的 N-羧基酐聚合来完成的，该聚合是由甲氧基 PEG-NH2 引发的，随后进行脱苄基反应。
结果
所得嵌段共聚物通过傅里叶变换红外光谱（FTIR）、氢核磁共振（H-NMR）和凝胶渗透色谱（SEC）进行了表征。通过芘荧光探针法、动态光散射（DLS）和透射电子显微镜（TEM）研究了 PIC 纳米胶的自组装性质，结果表明，在 PEG-b-PGlu 浓度/LMWC 重量比为 5:1 时，形成了均一的球形颗粒，平均粒径为 28nm。直接加载 SN38 后，药物溶解度提高了 40 倍以上，平均载药效率为 89%，载药量为 30%。PIC 纳米胶的 ζ 电位为+1mV，具有可接受的生物相容性，在鼠结直肠癌细胞（CT26 细胞系）中的细胞毒性优于游离药物。
结论
此外，PIC 纳米胶还能在生理条件下保护 SN38 免受水解降解。综上所述，经过精心调整的 PIC 纳米胶有望成为 SN38 传递的一种潜在生物相容的纳米载体。
Zotero 插件