具有梯级释药性能的核壳型双重载药微球

doi:10.16085/j.issn.1000-6613.2020-0608

摘要/Abstract

摘要：

分别利用单轴和同轴静电喷雾法成功制备出以聚乳酸-羟基乙酸共聚物（PLGA）为内核基质、聚乙烯吡咯烷酮（PVP）为外壳基质的核壳型双重载药微球，其中，抗菌药物盐酸万古霉素（VA）被包封于微球外壳，促成骨药物地塞米松（DA）被负载于微球内核。对载药微球的形貌结构、物理性质和体外释药性能进行了表征和分析。结果表明，当电喷前体PVP浓度为80g/L时，单轴和同轴静电喷雾方法均可得到大小均一、球形良好的核壳型微球。X射线衍射（XRD）和差示扫描量热（DSC）结果表明，DA晶体被成功包封于核壳型微球后转变为无定形状态。基于PVP的水溶性和PLGA的缓慢降解特性，两种核壳型载药微球都实现了壳层VA快速释放、内核DA缓慢释放的梯级释药性能。本文制备得到的具有梯级释药性能的核壳型载药微球在药物控释、组织工程等领域有很好的应用前景。

关键词: 核壳型微球, 单轴静电喷雾, 同轴静电喷雾, 双重载药, 梯级释药

Abstract:

Dual drug-loaded core-shell microspheres were successfully prepared by single and coaxial electrostatic spraying methods under mild conditions with poly(lactic acid-co-glycolic acid) (PLGA) as the core matrix and poly(vinylpyrrolidone) (PVP) as the shell matrix. Vancomycin hydrochloride (VA) as an antibacterial model drug was loaded into the PVP shell and osteogenic dexamethasone (DA) as an osteogenic model drug was loaded into the PLGA core. The results showed that when PVP concentration is 80g/L, both single and coaxial electrostatic spraying methods could obtain core-shell microspheres with good spherical shape and distinct core-shell structure. The results of X-ray diffraction (XRD) and differential scanning calorimeter (DSC) showed that DA is amorphous when it is encapsulated into the microspheres. Based on the water-solubility of PVP and the slow degradation of PLGA, these core-shell microspheres can achieve the rapid-release of VA and the sustained-release of DA. The programmed sequential release behavior of these dual drug-loaded core-shell microspheres endows them with potential applications in the drug controlled-release and tissue engineering.

Key words: core-shell microspheres, single electrostatic spraying, coaxial electrostatic spraying, dual drug-loading, programmed sequential release

中图分类号:

TQ469

尹微虹, 巨晓洁, 谢锐, 汪伟, 刘壮, 褚良银. 具有梯级释药性能的核壳型双重载药微球[J]. 化工进展, 2021, 40(2): 998-1007.

Weihong YIN, Xiaojie JU, Rui XIE, Wei WANG, Zhuang LIU, Liangyin CHU. Dual drug-loaded core-shell microspheres for programmed sequential release[J]. Chemical Industry and Engineering Progress, 2021, 40(2): 998-1007.

图/表 10

图1 核壳型双重载药微球的制备装置

图2 PLGA纳米颗粒的SEM图和粒径分布

表1 单轴电喷前体参数

微球	电喷产物编号	PVP浓度/g·L^-1	电喷前体黏度/mPa·s
核壳型空白微球	SBMs1	10	2.32
	SBMs2	20	2.85
	SBMs3	40	4.35
	SBMs4	80	8.71
	SBMs5	160	24.1
	SBMs6	240	57.44
核壳型载药微球	SDMs1	10	2.56
	SDMs2	20	3.16
	SDMs3	40	4.75
	SDMs4	80	9.67
	SDMs5	160	25.41
	SDMs6	240	60.23

表2 同轴电喷前体参数

微球	电喷产物编号	PVP浓度/g·L^-1	电喷前体黏度/mPa·s
核壳型空白微球	CBMs1	10	1.94
	CBMs2	20	2.5
	CBMs3	40	3.79
	CBMs4	80	7.49
	CBMs5	160	22.6
	CBMs6	240	50.7
核壳型载药微球	CDMs1	10	1.95
	CDMs2	20	2.46
	CDMs3	40	3.85
	CDMs4	80	8.03
	CDMs5	160	23.84
	CDMs6	240	53.16

图3 PVP浓度为80g/L时的静电喷雾

图4 单轴静电喷雾所得空白[（a)~(f）]和载药[（g)~(l）]产物的SEM图（标尺10μm）

图5 同轴静电喷雾所得空白[（a)~(f）]和载药[（g)~(l）]产物的SEM图（标尺10μm）

图6 PVP浓度为80g/L时两种核壳型载药微球的TEM图

图7 原材料和两种核壳型载药微球的物理性质

图8 两种核壳型载药微球在PBS缓冲溶液中的释药曲线

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