摘要：重组人白细胞介素-2(rhIL-2)具有促进免疫细胞增殖和分化的潜能， 可用于治疗肺癌。然而， rhIL-2半衰期短， 生物活性不稳定， 需要将其载入微球中进行缓释给药。本研究采用同轴静电喷涂技术制备了载rhIL-2的核壳微球。以量子点为示踪材料， 核层用壳聚糖做载体包裹rhIL-2和量子点偶联物， 壳层采用透明质酸做载体制备核壳复合微球。采用单因素法对载体浓度、电压、针孔内径、喷雾流量等因素进行了研究。优化了同轴静电喷雾法制备核壳微球的工艺参数。结果表明， 制备的核壳微球粒径在1.2–2.0 μm， 包封率和载药量分别为78.39% ± 1.96%和19.58 ± 2.76 μg/mg。体外释放实验显示微球释放效果较好， 无突释现象。该制剂的生物学活性实验表明， 核壳微球中的rhIL-2与游离蛋白药物具有相同的作用。体内成像分析也显示微球具有主动靶向性。本研究为rhIL-2靶向缓释微球的研制提供了理论依据。
文章目录
1. Introduction
2. Materials and methods
2.1. Experimental animals
2.2. Main reagents
2.3. Preparation of QD-protein conjugates
2.4. Optimization of process parameters for nuclear layer microsphere preparation using uniaxial electrostatic spray
2.5. Optimization of process parameters for coaxial electrostatic spray preparation of core-shell structure microspheres
2.6. Preparation of composite microspheres using core-shell structure (CS-rhIL-2-QDs-HA-MS)
2.7. Characterization of the properties of microspheres
2.7.1. Morphology and size distribution
2.7.2. Drug EE and DL capacity
2.7.3. Fluorescence stability analysis
2.7.4. Protein biological activity
2.7.5. In vitro release and kinetic study
2.7.6. Targeting effect of microspheres
3. Results and discussion
3.1. Screening and analysis of nuclear layer microsphere process
3.1.1. Effect of acetic acid concentration
3.1.2. Effect of PVA concentration
3.1.3. Effect of CS concentration
3.1.4. Effect of electric jet flow rate
3.1.5. Effect of voltage
3.1.6. Effect of acceptable distance parameters
3.1.7. Effect of pinhole inner diameter
3.2. Screening and analysis of core-shell microsphere process
3.2.1. Effect of sodium hyaluronate concentration
3.2.2. Effect of solvent ratio mixtures
3.2.3. Effect of receiving distance
3.3. Characterization of microspheres (CS-rhIL-2-QDs-HA-MS)
3.3.1. Analysis of morphology and size distribution
3.3.2. EE and DL capacity
3.3.3. Analysis of fluorescence stability
3.3.4. Analysis of protein biological activity
3.3.5. In vitro release and drug release kinetics
3.3.6. Targeting activities
4. Conclusions
