Preparation and in vitro Release of Multilayer Alginate Chitosan Microspheres Loading VEGF and Vancomycin†

doi:10.7503/cjcu20140992

Abstract

Abstract:

The core ball carrying vascular epithelial growth factor(VEGF) was first prepared by crosslinking of alginate and calcium. Then, chitosan, alginate, and chitosan again were coated on the surface of the core ball layer by layer using self-assembly technology, which constituted a multi-drug loaded release-controlled system at last, and vancomycin was loaded in the chitosan layer. The effect of the concentration of alginate, calcium and chitosan on microspheres’ morphology, size, drug loading and in vitro release was studied by an orthogonal experiment to find the best formula design. Morphologies of the surface and cross section and dia-meter were observed by scanning electron microscopy(SEM). Infrared absorption spectrum of the multilayer microspheres was also detected by Fourier transformed infrared spectrometer(FTIR). The result showed that the best concentrations of alginate, calcium and chitosan were 0.04, 0.15 and 0.01 g/mL, respectively. And in this case, the multilayer microspheres were typical spherical with smooth surface and the internal solid structure with a diameter ranging from 900 to 1100 μm. The entrapment efficiency of VEGF and vancomycin was 61.31% and 3.48%, respectively. In vitro, the release of VEGF could be sustained stably for up to 15.5 d with two releasing peak, which is surprising and exciting. As well, the release of vancomycin lasted for 4.5 d, which also meets the clinical needs. The research indicates that VEGF and vancomycin loaded multilayer microspheres possess good controlled release characteristics and have the potentials of controlling infection and promoting vascularization at the same time, which is hopeful for basic research and clinical application of tissue engineering bone(TEB).

Key words: Vascular epithelial growth factor, Vancomycin, Multilayer microspheres, Drug controlled release, Alginate, Chitosan

CLC Number:

O631

TrendMD:

YANG Junxing, WANG Qi, WANG Yuanyuan, HAN Shu, YAO Jiawei, SHAO Siqi, WANG Jinglong, LIU Zhihui, GUO Yupeng. Preparation and in vitro Release of Multilayer Alginate Chitosan Microspheres Loading VEGF and Vancomycin^†[J]. Chem. J. Chinese Universities, 2015, 36(5): 1025.

Figures/Tables 8

References 26

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Group	Concentration of SA(A)/ (g·mL^-1)	Concentration of CaCl₂(B)/ (g·mL^-1)	Concentration of CS(C)/ (g·mL^-1)
1	0.04	0.05	0.03
2	0.01	0.15	0.02
3	0.04	0.15	0.01
4	0.01	0.10	0.03
5	0.02	0.15	0.03
6	0.04	0.10	0.02
7	0.02	0.05	0.02
8	0.02	0.10	0.01
9	0.01	0.05	0.01

Group	Concentration of SA(A)/ (g·mL^-1)	Concentration of CaCl₂(B)/ (g·mL^-1)	Concentration of CS(C)/ (g·mL^-1)
1	0.04	0.05	0.03
2	0.01	0.15	0.02
3	0.04	0.15	0.01
4	0.01	0.10	0.03
5	0.02	0.15	0.03
6	0.04	0.10	0.02
7	0.02	0.05	0.02
8	0.02	0.10	0.01
9	0.01	0.05	0.01

Group	Level			EE of VEGF(%)	EE of VAN(%)	DL of VEGF(%)	DL of VAN(%)
Group	A/(g·mL^-1)			EE of VEGF(%)	EE of VAN(%)	B/(g·mL^-1)	C/(g·mL^-1)
1	0.04	0.05	0.03	49.4	0.970	7.20×10^-5	0.532
2	0.01	0.15	0.02	27.7	2.53	1.23×10^-4	4.20
3	0.04	0.15	0.01	61.3	3.48	5.90×10^-5	1.25
4	0.01	0.10	0.03	46.9	2.55	1.77×10^-4	3.61
5	0.02	0.15	0.03	47.4	3.68	7.80×10^-5	2.26
6	0.04	0.10	0.02	55.2	0.850	6.10×10^-5	0.351
7	0.02	0.05	0.02	64.5	2.36	1.35×10^-4	1.86
8	0.02	0.10	0.01	39.6	4.17	7.10×10^-5	2.81
9	0.01	0.05	0.01	32.8	6.05	1.50×10^-4	10.4

Group	Level			EE of VEGF(%)	EE of VAN(%)	DL of VEGF(%)	DL of VAN(%)
Group	A/(g·mL^-1)			EE of VEGF(%)	EE of VAN(%)	B/(g·mL^-1)	C/(g·mL^-1)
1	0.04	0.05	0.03	49.4	0.970	7.20×10^-5	0.532
2	0.01	0.15	0.02	27.7	2.53	1.23×10^-4	4.20
3	0.04	0.15	0.01	61.3	3.48	5.90×10^-5	1.25
4	0.01	0.10	0.03	46.9	2.55	1.77×10^-4	3.61
5	0.02	0.15	0.03	47.4	3.68	7.80×10^-5	2.26
6	0.04	0.10	0.02	55.2	0.850	6.10×10^-5	0.351
7	0.02	0.05	0.02	64.5	2.36	1.35×10^-4	1.86
8	0.02	0.10	0.01	39.6	4.17	7.10×10^-5	2.81
9	0.01	0.05	0.01	32.8	6.05	1.50×10^-4	10.4

EE of VEGF(%)				EE of VAN(%)				DL of VEGF(%)				DL of VAN(%)
K1	K2	K3	R	K1	K2	K3	R	K1	K2	K3	R	K1	K2	K3	R
55.3	50.5	35.8	19.5	1.77	3.40	3.71	1.94	6.40×10^-5	9.50×10^-5	1.50×10^-4	8.60×10^-5	0.710	2.31	6.06	5.35
45.5	47.3	48.9	3.47	3.23	2.52	3.13	0.710	8.70×10^-5	1.03×10^-4	1.19×10^-4	0.320×10^-5	2.57	2.26	4.26	2.00
47.9	49.1	44.6	4.54	2.40	1.91	4.57	2.65	1.09×10^-4	1.06×10^-4	9.30×10^-5	1.70×10^-5	2.13	2.14	4.82	2.68