budesonide palmitate | 102638-08-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: budesonide palmitate
• 英文别名: Budesonide-21-palmitate；(11I(2),16I+/-)-16,17-[Butylidenebis(oxy)]-11-hydroxy-21-[(1-oxohexadecyl)oxy]pregna-1,4-diene-3,20-dione；[2-[(1S,2S,4R,8S,9S,11S,12S,13R)-11-hydroxy-9,13-dimethyl-16-oxo-6-propyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-8-yl]-2-oxoethyl] hexadecanoate
• CAS: 102638-08-4
• 化学式: C₄₁H₆₄O₇
• 分子量: 668.955
• InChiKey: KZHFZMFWUHTKDG-QFDZWVBESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.4
• 重原子数：
  48
• 可旋转键数：
  20
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  99.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  左布地奈德 、 棕榈酰氯 在 吡啶 、 盐酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 24.0h， 生成 budesonide palmitate
  参考文献：
  名称：

  Mannosylation of budesonide palmitate nanoprodrugs for improved macrophage targeting

  摘要：

  In a strategy to improve macrophage targeting of glucocorticoids (GCs) for anti-inflammatory therapy, a so-called nanoprodrug of budesonide palmitate decorated by mannose moieties was designed. The synthesis of budesonide palmitate (BP) was obtained by esterification and mannosylated lipid (DSPE-PEG-Man) by reacting 1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine (DSPE)-polyethylene glycol-amine and α-D-mannopyranosylphenyl isothiocyanate (MPITC). Nanoparticles were formulated by emulsion-evaporation and different ratios of mannosylated lipid were introduced in the formulation of BP nanoprodrugs. Using up to 75% of DSPE-PEG-man (75/25) led to 200 nm particles with a polydispersity index below 0.2, a negative zeta potential ranging from -10 to -30 mV, and one-month stability at 4°C. The encapsulation efficiency of BP approached 100% proving that the prodrug was associated with the particles, leading to a final BP loading of 50-to 60% (w/w). The lectin agglutination test confirmed the availability of mannose on the nanoprodrug surface. Nanoprodrug uptake by RAW 264.7 macrophages was observed by confocal microscopy and flow cytometry. After 24 and 48 hours of incubation, a significantly greater internalization of mannosylated nanoparticles as compared to PEGylated nanoparticles was achieved. The mannose receptor-mediated uptake was confirmed by a mannan inhibition study. After LPS-induced inflammation, the anti-inflammatory effect of mannosylated nanoparticles was assessed. After 48 hours of incubation, cytokines (MCP-1 and TNFα) were reduced demonstrating that the functionalization of nanoprodrugs is possible and efficient.

  DOI：

  10.1016/j.ejpb.2021.12.001

文献信息

• Mannosylation of budesonide palmitate nanoprodrugs for improved macrophage targeting
  作者：Ludmila Pinheiro do Nascimento、Nicolas Tsapis、Franceline Reynaud、Didier Desmaële、Laurence Moine、Juliette Vergnaud、Sonia Abreu、Pierre Chaminade、Elias Fattal

  DOI：10.1016/j.ejpb.2021.12.001

  日期：2022.1

  In a strategy to improve macrophage targeting of glucocorticoids (GCs) for anti-inflammatory therapy, a so-called nanoprodrug of budesonide palmitate decorated by mannose moieties was designed. The synthesis of budesonide palmitate (BP) was obtained by esterification and mannosylated lipid (DSPE-PEG-Man) by reacting 1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine (DSPE)-polyethylene glycol-amine and α-D-mannopyranosylphenyl isothiocyanate (MPITC). Nanoparticles were formulated by emulsion-evaporation and different ratios of mannosylated lipid were introduced in the formulation of BP nanoprodrugs. Using up to 75% of DSPE-PEG-man (75/25) led to 200 nm particles with a polydispersity index below 0.2, a negative zeta potential ranging from -10 to -30 mV, and one-month stability at 4°C. The encapsulation efficiency of BP approached 100% proving that the prodrug was associated with the particles, leading to a final BP loading of 50-to 60% (w/w). The lectin agglutination test confirmed the availability of mannose on the nanoprodrug surface. Nanoprodrug uptake by RAW 264.7 macrophages was observed by confocal microscopy and flow cytometry. After 24 and 48 hours of incubation, a significantly greater internalization of mannosylated nanoparticles as compared to PEGylated nanoparticles was achieved. The mannose receptor-mediated uptake was confirmed by a mannan inhibition study. After LPS-induced inflammation, the anti-inflammatory effect of mannosylated nanoparticles was assessed. After 48 hours of incubation, cytokines (MCP-1 and TNFα) were reduced demonstrating that the functionalization of nanoprodrugs is possible and efficient.