Stearoyl-Chitosan Coated Nanoparticles Obtained by Microemulsion Cold Dilution Technique
Stearoyl-Chitosan Coated Nanoparticles Obtained by Microemulsion Cold Dilution Technique
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DOI：
10.3390/ijms19123833
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发表时间：
2018-12-01
影响因子：
5.6
通讯作者：
Gallarate, Marina
中科院分区：
文献类型：
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作者：
Chirio, Daniela;Peira, Elena;Gallarate, Marina
壳聚糖是一种赋形剂，由于其积极的特性，如粘膜粘附和打开上皮紧密连接的能力，已在研究工作中进行了深入研究。本文合成了脂溶性的硬脂酰壳聚糖（ST-CS），并将其锚在脂质纳米粒上，采用微乳冷稀释法制备了ST-CS包被纳米粒（ST-CS-NP）。以姜黄素（Curcumin，CURC）为模型药物。CURC-ST-CS-NP通过尺寸分析、zeta电位、药物包封、药物释放进行表征;在体外对人脐静脉内皮细胞（HUVEC）进行细胞毒性测试以研究其细胞毒性，并对人胰腺癌细胞（PANC-1）进行抑制能力测试;在大鼠中进行测试以确定CURC血液特征和生物分布。CURC-ST-CS-NP的平均直径在200-400 nm范围内，CURC包封率高达73%。这些系统在所有测试的稀释度下对HUVEC细胞都没有显示出细胞毒性，并且显示在5和10 μ M CURC下对PANC-1细胞比游离CURC溶液更有效。血液特征研究表明，与CURC溶液相比，由于NP的某种隐形特性（可能归因于亲水性壳聚糖涂层），NP中的CURC包封延长了药物在体循环中的持久性。生物分布研究表明，当施用CURC-ST-CS-NP时，RES器官中的CURC浓度较小。
Chitosan is an excipient which has been studied thoroughly in research works thanks to its positive characteristics such as muco-adhesiveness and ability to open epithelial-tight-junctions. In this article, lipophilic stearoyl chitosan (ST-CS) was synthetized in order to anchor this polymer to lipid nanoparticles and prepare ST-CS-coated nanoparticles (ST-CS-NP) using the microemulsion cold dilution technique. Curcumin (CURC) was used as model drug. CURC-ST-CS-NP were characterized by dimensional analysis, zeta potential, drug entrapment, drug release; tested in vitro on Human Umbilical Vein Endothelial Cell (HUVEC) cells to study its cytotoxicity and on human pancreatic cancer cells (PANC-1) to determine inhibition ability; tested in rats to determine CURC blood profiles and biodistribution. CURC-ST-CS-NP had mean diameters in the range 200-400 nm and CURC entrapment up to 73%. These systems did not show cytotoxicity on HUVEC cells at all tested dilutions and revealed to be more effective than free CURC solution on PANC-1 cells at 5 and 10 mu M CURC. Blood profile studies evidenced as CURC entrapment in NP prolonged the permanence of drug in the systemic circulation compared to CURC solution due to a certain stealth property of NP, probably attributable to hydrophilic chitosan coating. Biodistribution studies showed a smaller CURC concentration in RES organs when CURC-ST-CS-NP were administered.