Photodegradable poly(ester amide)s for indirect light-triggered release of paclitaxel

Abstract

A photodegradable poly(ester amide) was developed. An amphiphilic graft copolymer derivative with paclitaxel conjugated via ester linkages formed micelles that released paclitaxel in response to UV light.

Progress in Research of Photo-controlled Drug Delivery Systems

“…包载 Tagalsin G (250 μg•mL -1 )的纳米颗粒对 RAW 264.7 细胞几乎没有细胞毒性(9%), 而在光照情况下, 细胞死 亡率达到了 67%, 表明该纳米颗粒具有很好的光触发释 药的效果. Soleimani 等 [44] 制备了聚合物主链含有 ONB 的聚酯酰胺(PEA)纳米颗粒(图 7), 10 min 的 UV 光照射 获得了 20%的药物释放(无光照组释放量小于 3%). Yan 等 [45] 用含有光响应基团 ONB 的聚丙烯酰胺-聚(乙二醇) 交联剂制备了网格状的水凝胶分子(图 8a), 结合上转换 纳米颗粒(upconversion nanoparticles UCNPs)实现了用 NIR 光作为刺激源控制药物释放的目的, 在 NIR 光的照 射下, 水凝胶中的 ONB 基团断裂后, 通过凝胶-溶胶 图 6 (a)光敏感聚氨酯分子结构; (b)疏水性模型药物和光敏感聚氨酯 自组装成载药纳米颗粒, 在 UV 照射下, 聚合物主链降解释放药物 [43] Figure 6 (a) The chemical structure of light-sensitive polyurethane molecules; (b) the drug-loaded nanoparticles are formed by the hydrophobic model drug and the light-sensitive polymer, which are degraded to release the drug under UV irradiation [43] 图 7 (a)光敏感聚酯酰胺单体分子结构; (b)UV 光诱导光敏感聚酯酰 胺主链断裂释放药物分子 [44] Figure 7 (a) The chemical structure of light-sensitive polyester amide molecules; (b) the light-sensitive nanoparticles are broken to release drug under UV irradiation [44] 图 8 (a)光敏感水凝胶分子的化学结构; (b) NIR 光触发的光敏感水凝 胶降解示意图 [45] Figure 8 (a) The chemical structure of light-sensitive hydrogel; (b) Schematic illustration of the NIR-light-triggered degradation of a light-sensitive hydrogel using the UV light generated by encapsulated UCNPs [45] (gel-sol)转变破坏整个凝胶的结构, 释放所封装的生物 大分子(图 8b), 实验结果显示在 NIR 光(980 nm, 5 W)照 射 57 min 后装载的生物大分子(胰蛋白酶)累积释放量达 到了 72%, 这些结果说明掺杂 UCNPs 的光敏感水凝胶 能够响应 NIR 光刺激, 释放装载的生物活性分子.…”

Covalent drug immobilization in poly(ester amide) nanoparticles for controlled release

“…As previously reported, PEA-Asp (Figure 3), composed of a 9:1 molar ratio of L-phenylalanine and L-aspartic acid monomers, provides carboxylic acid functional handles for the conjugation of drugs or other reagents. [29,35,36] Thus, PEA-Asp was prepared as previously reported (Figure 3). [29] Rhod-OH was also prepared by a previously reported procedure, [51] and was coupled to PEA-Asp in dry CH 2 Cl 2 using DCC in the presence of DMAP and DPTS.…”

“…[16,22,23,[25][26][27][28] In addition, the ability to incorporate amino acids such as L-lysine and L-aspartic acid, which have pendant functional groups, was recently demonstrated through the use of protecting group strategies, and offers the possibility of functionalizing these pendant groups on the polymer after protecting group removal. [21,29,30] PEAs containing a-amino acids have recently been investigated in applications including particle- [31][32][33] and micelle-based [34][35][36] drug delivery, hydrogels, [18,37] vascular grafts, [38] and vascular tissue engineering. [39][40][41] In these applications, they have been shown to be well tolerated by cells, non-immunogenic, and supporting of cell growth.…”

“…[23,24] There are several different backbone structures for PEAs, but PEAs containing a-amino acids are of particular interest because of their biomimetic nature, as a-amino acids are the main constituents of proteins. [21,29,30] PEAs containing a-amino acids have recently been investigated in applications including particle- [31][32][33] and micelle-based [34][35][36] drug delivery, hydrogels, [18,37] vascular grafts, [38] and vascular tissue engineering. [21,29,30] PEAs containing a-amino acids have recently been investigated in applications including particle- [31][32][33] and micelle-based [34][35][36] drug delivery, hydrogels, [18,37] vascular grafts, [38] and vascular tissue engineering.…”

Photo-responsive polymeric micelles and prodrugs: synthesis and characterization

“…[2][3][4][5] However, many drug delivery systems face strong limitations that potentially affect their further translation to clinical tests: the burst release in which a large fraction of adsorbed drug is rapidly released aer administration and the inadequate drug loading which usually necessitates a high concentration of nanocarriers to obtain a noticeable therapeutic effect. These major obstacles may be overcome by applying the polymer prodrug approach, where the drug is covalently conjugated onto polymer backbones and side chains through labile linkers that can be cleaved in certain conditions.…”