新型中空羟基磷灰石微球/壳聚糖复合药物载体用于药物控制释放

doi:10.15541/jim20150488

摘要/Abstract

摘要：

利用中空羟基磷灰石微球和pH敏感型壳聚糖溶液制备了一种具有良好药物缓释和pH敏感型特性的新型复合药物载体材料。采用组分为19Na₂O-17CaO-64B₂O₃(wt%)的硼酸盐玻璃在磷酸盐溶液中的原位转化反应制备了多壳层介孔中空HA微球, 通过SEM、SEM-EDS、XRD和FTIR等方法对产物微球进行表征。结果表明: 微球具有多层介孔中空结构, 且属于B型碳酸HA。释药结果表明: 中空HA微球在释药初期产生了突释现象, 包覆壳聚糖后, 复合载体的释药量和释药速率显著下降。与此同时, 复合药物载体在不同pH的PBS溶液中表现出pH敏感型药物释放特征, 利用浓度20 g/L的壳聚糖溶液包覆的复合载体在pH为6.0、7.4和8.5的PBS溶液中的药物累积释放率分别为85.63%、65.85%和71.85%。

关键词: 中空羟基磷灰石(HA)微球, 复合药物载体, pH敏感, 壳聚糖

Abstract:

A novel composite drug carrier with excellent sustained and pH-sensitive release performance was prepared by mixing hollow hydroxyapatite (HA) microspheres and chitosan solution with pH-sensitive characteristics. The hollow HA microspheres with mesopores filled on their multilayered spherical shell were obtained by converting borate glass with a novel composition of 19Na₂O-17CaO-64B₂O₃(wt%). The structure, phase composition and morphology of HA microspheres were characterized by SEM, SEM-EDS, XRD, FTIR and N₂ adsorption-desorption measurements. The results indicated that the HA microspheres were B-type carbonated HA with hollow structure, in which the carbonate ions occupied the phosphate sites. The drug release results indicated that the HA microspheres generated burst release at initial stage. Coating the hollow HA microspheres with chitosan (CS) reduced the vancomycin release amount and release rate significantly. Meanwhile, the release profile of vancomycin into PBS with different pH value indicated that the CS-coated composite drug carrier shows pH-sensitive release property. The cumulative percentage of vancomycin released into PBS from the CS (20 g/L)-coated composite drug carrier was 85.63%, 65.85% and 71.85% for pH 6.0, 7.4, 8.5, respectively.

Key words: hollow hydroxyapatite (HA) microspheres, composite drug carrier, pH-sensitive, chitosan

中图分类号:

TQ171

朱开平, 孙静, 叶松, 周杰, 王会, 王德平. 新型中空羟基磷灰石微球/壳聚糖复合药物载体用于药物控制释放[J]. 无机材料学报, 2016, 31(4): 434-442.

ZHU Kai-Ping, SUN Jing, YE Song, ZHOU Jie, WANG Hui, WANG De-Ping. A Novel Hollow Hydroxyapatite Microspheres/Chitosan Composite Drug Carrier for Controlled Release[J]. Journal of Inorganic Materials, 2016, 31(4): 434-442.

图/表 12

Fig. 1 SEM image of the as-prepared microspheres with a cross-section in the inset

Fig. 2 Surface SEM images of the hollow HA microspheres (a) Dried at 60℃; (b) Sintered at 600℃ The inset in (a) and (b) show the high magnification image of the surface

Fig. 3 The N2 adsorption-desorption isotherm (a) and the pore size distribution (b) of the microspheres treated at different temperatures

Table 1 The surface characteristics and pore structure parameters of the microspheres

Sample	SA/(m²·g^-1)	PV/(cm³·g^-1)	PS/nm
60℃	55.32	0.21	15.38
600℃	31.17	0.17	28.29

Fig. 4 XRD patterns (a) and FTIR spectrum (b) of the microspheres treated at different temperatures

Fig. 5 EDS spectrum of the shell wall of the hollow HA microspheres (a) Select location (black frame) of the EDS; (b) EDS spectrum

Fig. 6 XRD patterns (a) and FTIR spectra (b) of the CS-coated composite drug carrier

Fig. 7 SEM images of the surface and the cross-section of the CS-coated composite drug carrier (a) Surface of the CS (20 g/L)-coated; (b) Cross-section of the CS (20 g/L)- coated; (c) Surface of the CS (30 g/L)-coated; (d) Cross-section of the CS (30 g/L)-coated

Fig. 8 The cumulative release percentage of vancomycin from the hollow HA microspheres, CS (20 g/L)-coated and CS (30 g/L)-coated composite drug carrier into PBS as a function of time

Fig. 9 The cumulative release percentage of vancomycin into PBS with different pH from the hollow HA microspheres (a), the CS (20 g/L)- coated composite drug carrier (b) and the CS (30 g/L)-coated composite drug carrier (c)

Fig. 10 Physical photos of the CS (20 g/L)-coated composite drug carrier at special time points immersing in PBS with different pH

Fig. 11 SEM image of the CS (20 g/L)-coated HA microspheres after immersing in PBS with the high pH 8.5. Red arrows indicate the hollow HA microspheres; black arrows indicate the chitosan gel

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