Preparation and Characterization of Shell Cross-linked PLGA Nanoparticles with pH-responsiveness for Drug Delivery

Sheng-long Gan; Zhen-ping Lu; Zhe Yang; Jie Liu

doi:10.11777/j.issn1000-3304.2015.14234

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Preparation and Characterization of Shell Cross-linked PLGA Nanoparticles with pH-responsiveness for Drug Delivery

Research Article | 更新时间：2021-03-19

- Preparation and Characterization of Shell Cross-linked PLGA Nanoparticles with pH-responsiveness for Drug Delivery
- Acta Polymerica Sinica Issue 2, Pages: 228-235(2015)
- 作者机构：
  
  中山大学工学院生物医学工程系,广州,510006
- 作者简介：
- 基金信息：
- DOI：10.11777/j.issn1000-3304.2015.14234
  CLC：
- Published：20 February 2015，
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Sheng-long Gan, Zhen-ping Lu, Zhe Yang, Jie Liu. Preparation and Characterization of Shell Cross-linked PLGA Nanoparticles with pH-responsiveness for Drug Delivery. [J]. Acta Polymerica Sinica (2):228-235(2015)
DOI：

Sheng-long Gan, Zhen-ping Lu, Zhe Yang, Jie Liu. Preparation and Characterization of Shell Cross-linked PLGA Nanoparticles with pH-responsiveness for Drug Delivery. [J]. Acta Polymerica Sinica (2):228-235(2015) DOI： 10.11777/j.issn1000-3304.2015.14234.

摘要

首先采用一次乳化法制备出PLGA[聚(乳酸-羟基乙酸)]纳米微球

并通过静电吸附将阳离子聚合物壳聚糖修饰到PLGA微球表面

然后以香草醛为交联剂对壳聚糖进行化学交联

得到一种壳交联的pH响应型纳米微球(PCV)

微球粒径为(277.60 38.01)nm

表面电位为(21.60 4.51)mV. 微球稳定性评价结果显示微球在24 h内粒径变化较小;流式细胞仪检测显示细胞对PCV微球的摄取量比未经修饰的PLGA微球的摄取量高;空白微球细胞毒性实验表明在空白微球浓度小于80 g/mL时细胞的存活率达93.24%.以多西他赛(DTX)为模型药物进行包载

该纳米微球DTX的载药率为7.48%

包封率为34.98%;体外药物释放实验显示

该微球在pH=5.0环境下孵育90 h的药物积累释放率达58.66%

而在pH=7.4的环境下的药物积累释放率为50.63%;此外

载DTX微球毒性试验结果表明该载药微球对A549肺癌细胞有较强的杀伤作用

其IC50 值可达0.0009 g/mL.

Abstract

To obtain the shell cross-linked PLGA-NPs (PCV-NPs)

PLGA nanoparticles (PNPs) were prepared by emulsification technique first. Subsequently

chitosan was coated on the surface of the PLGA-NPs via the electrostatic interaction. Finally

vanillin

a non-toxic chemical cross-linker

was chosen to react with the chitosan to form Schiff base on the surface of nanoparticles. Size and zeta potential of PCV-NPs detected by Malvern Zetasizer Nano ZS90 were in the range of (277. 60 38. 01) nm and (21. 60 4. 51) mV

respectively. Besides

SEM images show PCV-NPs have smooth and spherical morphology. Infrared spectroscopy was used to detect the chemical structure of all the NPs

and the characteristic vibrating peak of the Schiff base at 1640 cm-1 emerged on the spectral line of PCV-NPs. PCV-NPs performed excellent stability within 24 h incubation in the serum containing medium. The cellular uptake study was performed using hydrophobic fluorescein coumarin 6

the results indicated coumarin 6-loaded PCV-NPs possessed better transmembrane transport capacity compared with P-NPs. And the cytotoxicity studies demonstrated that there was no obvious cytotoxicity of blank PCV-NPs. Furthermore

docetaxel

a model drug

was encapsulated into PCV-NPs with high drug loading (7. 48%) and entrapment efficiency (34. 98%). In addition

the DTX cumulative release of DTX-loaded PCV-NPs was 58. 66% after 90 h of incubation at pH 5. 0. In comparison

the drug release was reduced to 50. 63% at pH 7. 4. DTX-loaded PCV-NPs showed efficient cell killing ability after 48 h incubation with A549 cells

the IC50 value of which was 0. 0009 g/mL.

关键词

PLGA微球壳聚糖香草醛壳交联pH环境响应型

Keywords

PLGA nanoparticlesChitosanVanillinShell crosslinkedpH-responsible

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Related Institution

College of Food Science and Technology, Nanjing Agricultural University

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Key Laboratory of Bio-based Material Science and Technology of Ministry of Education, College of Materials Science and Engineering, Northeast Forestry University

Department of Pharmaceutical and Biological Engineering, School of Chemical Engineering, Sichuan University

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