42 5 ( ) Vol.42 No.5 2011 5 Journal of Central South University (Science and Technology) May 2011 / 1, 2 1 1 1 (1. 430070 2. 430070) ph=11 W/O / / 1~10 µm 38.23% 54.21% 3 d 82% / R318 A 1672 7207(2011)05 1232 06 Preparation and performance of drug-loaded nano-hydroxyapatite/chitosan microspheres LI Xiang-nan 1, 2, CHEN Xiao-ming 1, PENG Zhi-ming 1, LI Shi-pu 1 (1. Biomedical Materials and Engineering Research Center, Wuhan University of Technology, Wuhan 430070, China; 2. College of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, China) Abstract: Nano-hydroxyapatite and chitosan were selected as matrix to prepare a novel metronidazole sustained release microsphere for bone tissue recovery. Aciform nano-hydroxyapatite was synthesized in ethanol medium (ph=11) using polyacrylic acid as dispersant. Metronidazole-loaded chitosan/hydroxyapatite composite microspheres were prepared by water in oil emulsion cross-linking method. The results show that the size of as-fabricated composite microspheres is mainly distributed from 1 to 10 µm, and hydroxyapatite and metronidazole are embedded very well by chitosan. The average drug loading is 38.23%, the average entrapment efficiency is 54.21%, and the cumulative release rate to metronidazole is near 82% during 3 d. The composite microspheres are spherical and distributed uniformly in diameter with a good property for the slow-release of metronidazole, which have great potential in drug delivery system. Key words: sustained release microsphere; metronidazole; nano-hydroxyapatite; chitosan 1978 [1] (HAP) 2010 01 252010 05 20 (50872099) (1977 ) 15327392976 E-mail: xiangnanlidong@163.com
5 / 1233 [2 6] HAP HAP [7] (CS) [8 9] [10 13] [14 16] HAP / HAP 1 1.1 92% 8 10 5 1.2 5.93 g Ca(NO 3 ) 2 4H 2 O 50%( ) 150 ml 1 2.0 g (NH 4 ) 2 HPO 4 50% 150 ml 2 2 1 ( 1 000 r/min) (PAA) 2.0 mol/l ph ph 11.0 3 h( ) 12 h 3 50 1.3 /HAP /HAP 60 ml 2%( ) 1.5 g 1:1 160 ml 30 min 5 ml span80 5 ml 25%( ) 50 10 h 3 50 /HAP 1.4 /HAP 1:1:1 /HAP 1.5 X (XRD, D/Max-IIIA, Rigaku, Japan) (TEM, JEM-2100F, JEOL, Japan) (SEM, H-600 STEM/EDX PV9100, HITACHI, Japan) EDS KBr (FT-IR, Nicolet Nexus 670) /HAP 1.6 ( UV2550 ) 50 mg 500 ml 0 1.0 2.0 3.0 3.5 4.0 6.0 8.0 ml 25 ml 0 4 8 12 16 24 32 mg/l 200~800 nm 50 mg 100 ml 24 h 3 ml 25 ml 320 nm X=(ρ/60) 100% ρ mg/l X η = ( Xm / M ) 100% η M m
1234 ( ) 42 1.7 6 200 ml ph 7.4 37 100 r/min 1.2 g 6 2 ml 0.8 µm 2 ml 2 ml 10 ml 320 nm 2 Fig.2 TEM image of hydroxyapatite crystals 2 2.1 X X 1 1 (JCPDS73-0293) HAP (002) (211) (112) (300) (202) (213) (310) (002) (211) (300) 2.2 2 2 3.0~4.0 5 nm 100 nm 1 X Fig.1 X-ray diffraction pattern of hydroxyapatite 2.3 EPS 3 3 SEM 1~10 µm 3(e)C O Ca P CS HAP HAP 3(f) N Ca P N EDS N HAP HAP Ca P 2.4 CS HAP FTIR 4 4 CS 1 649 cm 1 ( C=O ) 1 599 cm 1 ( ) 3 450 cm 1 O H NH 2 N H 474 571 601 962 1 032~1 087 cm 1 3 4 PO 1 634 3 000~3 700 cm 1 OH 630 3 570 cm 1 HAP CS 3 450 cm 1 O H N H
5 / 1235 (a), (b) (c), (d) (e) EDS (f) EDS 3 EDS Fig.3 SEM images and EDS spectra of microspheres CS HAP HAP 1 599 cm 1 (1 649 cm 1 ) CS NH 2 HAP OH HAP CS CS HAP HAP CS 2.5 5 5 320 nm 320 nm y 0.051 68x 0.020 80 (x mg/l) r 0.999 9 0~32 mg/l 3 38.23% 54.21% 2.6 6 6 0~72 h 10 h 21.02% 35 h 60%
1236 ( ) 42 55 h 80% 55 h 3 d 0.826 5 6 - / Fig.6 Cumulative release curve of metronidazole-loaded HAP/CS composite microspheres 1 CS 2 HAP 3 4 CS HAP FTIR Fig.4 Fourier transform infrared spectra of CS, HAP and HAP/CS microspheres (a) (b) 5 Fig.5 UV spectrum of metronidazole and standard curve 3 8 µm 50% ph 11 30 nm 100 nm 3(a) 3(b) 0.1 g
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