Preparation and performance of drug-loaded nano-hydroxyapatite/chitosan microspheres

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1 42 5 ( ) Vol.42 No Journal of Central South University (Science and Technology) May 2011 / 1, ( ) ph=11 W/O / / 1~10 µm 38.23% 54.21% 3 d 82% / R318 A (2011) 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 , China; 2. College of Chemical Engineering, Wuhan University of Technology, Wuhan , 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) ( ) (1977 ) xiangnanlidong@163.com

2 5 / 1233 [2 6] HAP HAP [7] (CS) [8 9] [10 13] [14 16] HAP / HAP % g Ca(NO 3 ) 2 4H 2 O 50%( ) 150 ml g (NH 4 ) 2 HPO 4 50% 150 ml ( r/min) (PAA) 2.0 mol/l ph ph h( ) 12 h /HAP /HAP 60 ml 2%( ) 1.5 g 1:1 160 ml 30 min 5 ml span80 5 ml 25%( ) 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 ml 25 ml 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

3 1234 ( ) ml ph 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 X X 1 1 (JCPDS ) HAP (002) (211) (112) (300) (202) (213) (310) (002) (211) (300) ~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 cm 1 ( C=O ) cm 1 ( ) cm 1 O H NH 2 N H ~1 087 cm PO ~3 700 cm 1 OH cm 1 HAP CS cm 1 O H N H

4 5 / 1235 (a), (b) (c), (d) (e) EDS (f) EDS 3 EDS Fig.3 SEM images and EDS spectra of microspheres CS HAP HAP cm 1 (1 649 cm 1 ) CS NH 2 HAP OH HAP CS CS HAP HAP CS nm 320 nm y x (x mg/l) r ~32 mg/l % 54.21% ~72 h 10 h 21.02% 35 h 60%

5 1236 ( ) h 80% 55 h 3 d / 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 nm 100 nm 3(a) 3(b) 0.1 g

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