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Frontiers of Materials Science

ISSN 2095-025X

ISSN 2095-0268(Online)

CN 11-5985/TB

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2018 Impact Factor: 1.701

Front Mater Sci    2011, Vol. 5 Issue (4) : 367-378    https://doi.org/10.1007/s11706-011-0146-0
RESEARCH ARTICLE
Biocompatibility and characteristics of chitosan/cellulose acetate microspheres for drug delivery
Hui-Yun ZHOU1,2(), Dong-Ju ZHOU1, Wei-Fen ZHANG2,3, Ling-Juan JIANG1, Jun-Bo LI1, Xi-Guang CHEN2()
1. Chemical Engineering and Pharmaceutics College, Henan University of Science and Technology, Luoyang 471003, China; 2. College of Marine Life Science, Ocean University of China, Qingdao 266003, China; 3. Department of Pharmaceutics, Weifang Medical College, Weifang 261042, China
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Abstract

In this work, chitosan/cellulose acetate microspheres (CCAM) were prepared by the method of W/O/W emulsion with no toxic reagents. The microspheres were spherical, free flowing, and non-aggregated, which had a narrow size distribution. More than 90% of the microspheres had the diameter ranging from 200 to 280 μm. The hemolytic analysis indicated that CCAM was safe and had no hemolytic effect. The implanted CCAM did not produce any significant changes in the hematology of Sprague-Dawley (SD) rats, such as white blood cell, red blood cell, platelet, and the volume of hemoglobin. In addition, the levels of serum alanine aminotransferase, blood urea nitrogen, and creatinine had no obvious changes in SD rats implanted with CCAM, surger thread, or normal SD rats without any implantation. Thus, the CCAM had good blood compatibility and had no hepatotoxicity or renal toxicity to SD rats. Furthermore, CCAM with or without the model drug had good tissue compatibility with respect to the inflammatory reaction in SD rats and showed no significant difference from that of SD rats implanted with surgery thread. CCAM shows promise as a long-acting delivery system, which had good biocompatibility and biodegradability.

Keywords chitosan      cellulose acetate      CCAM      blood compatibility      tissue compatibility     
Corresponding Author(s): ZHOU Hui-Yun,Email:zhouhuiyun@hotmail.com (H.Y.Z.); CHEN Xi-Guang,Email:xgchen@ouc.edu.cn (X.G.C.)   
Issue Date: 05 December 2011
 Cite this article:   
Hui-Yun ZHOU,Dong-Ju ZHOU,Wei-Fen ZHANG, et al. Biocompatibility and characteristics of chitosan/cellulose acetate microspheres for drug delivery[J]. Front Mater Sci, 2011, 5(4): 367-378.
 URL:  
https://academic.hep.com.cn/foms/EN/10.1007/s11706-011-0146-0
https://academic.hep.com.cn/foms/EN/Y2011/V5/I4/367
Fig.1  SEM images of microspheres: CCAM without model drug; CCAM-loaded RT.
Fig.2  Size distribution of CCAM (mean±S.D., = 5).
SampleOptical density (mean±S.D.)Rate of hemolysis /%
Distilled water1.446±0.051+control
Physiological saline0.046±0.006-control
Chitosan0.101±0.0123.96
Cellulose acetate0.069±0.0081.67
Blank CCAM0.087±0.0132.92
CCAM-loaded RT0.081±0.0102.47
Tab.1  Hemolytic activity of CCAM and materials (mean±S.D., = 3)
TimeHematology parameterValue
Normal control groupNegative control groupExperimental group IExperimental group II
4 daysWBC content /(109 L-1)4.3±0.93.7±1.23.6±0.93.4±1.4
RBC content /(1012 L-1)5.05±1.396.33±1.676.05±1.676.16±0.78
HGB content /(g·L-1)100±8128±13118±9119±11
PLT content /(109 L-1)366±121222±101542±98467±121
1 weekWBC content /(109 L-1)3.9±1.14.2±0.83.0±1.32.7±1.0
RBC content /(1012 L-1)5.65±1.845.79±1.011.95±1.563.67±1.37
HGB content /(g·L-1)110±10121±12129±1173±9
PLT content /(109 L-1)540±220305±158471±123236±178
2 weeksWBC content /(109 L-1)2.1±0.84.2±1.13.2±1.46.2±0.9
RBC content /(1012 L-1)5.74±1.584.30±0.786.38±1.136.17±0.74
HGB content /(g·L-1)122±1188±14126±9123±15
PLT content /(109 L-1)590±246326±212349±189308±166
4 weeksWBC content /(109 L-1)8.9±0.77.1±0.53.9±1.410.7±0.8
RBC content /(1012 L-1)5.90±1.916.10±1.315.46±0.855.88±1.11
HGB content /(g·L-1)130±13123±17109±9123±10
PLT content /(109 L-1)319±135541±179388±217625±136
6 weeksWBC content /(109 L-1)4.2±1.24.4±1.55.9±0.74.5±0.9
RBC content /(1012 L-1)5.49±2.112.17±2.565.41±1.664.86±1.91
HGB content /(g·L-1)105±9102±13112±18117±20
PLT content /(109 L-1)329±164206±232296±209264±175
8 weeksWBC content /(109 L-1)6.2±1.43.6±0.94.2±1.44.8±0.7
RBC content /(1012 L-1)5.16±1.552.47±2.156.13±1.346.15±1.21
HGB content /(g·L-1)117±1594±19124±21132±13
PLT content /(109 L-1)557±187259±123522±177234±198
12 weeksWBC content /(109 L-1)2.1±0.74.1±0.92.6±1.22.7±1.3
RBC content /(1012 L-1)3.88±1.654.33±1.872.16±1.745.65±1.12
HGB content /(g·L-1)83±1288±18125±24124±21
PLT content /(109 L-1)936±123418±167317±148442±213
Tab.2  Hematology parameters of rats in different times postoperatively (mean±S.D., = 3)
TimeClinical biochemistry parameterValue
Normal control groupNegative control groupExperimental group IExperimental group II
4 daysALT content /(U·L-1)25.86±9.1350.07±10.1141.09±8.7943.53±9.26
BUN content /(mmol·L-1)4.79±1.246.07±1.424.04±1.314.21±1.05
Cr content /(μmol·L-1)47.43±8.1284.31±9.3263.03±8.9664.77±7.98
1 weekALT content /(U·L-1)37.69±8.8343.59±9.1334.05±9.4244.98±9.82
BUN content /(mmol·L-1)3.84±1.252.52±1.967.59±1.193.72±1.45
Cr content /(μmol·L-1)57.72±7.1251.32±8.1145.89±8.3444.01±9.14
2 weeksALT content /(U·L-1)43.18±8.2245.74±9.7744.77±9.3550.43±8.65
BUN content /(mmol·L-1)4.29±1.335.06±1.073.85±1.873.78±1.51
Cr content /(μmol·L-1)55.35±7.6655.56±8.1263.05±8.5657.88±7.98
4 weeksALT content /(U·L-1)64.66±9.17136.7±9.3754.59±8.1127.51±8.64
BUN content /(mmol·L-1)5.58±1.668.74±1.256.09±1.784.09±1.09
Cr content /(μmol·L-1)72.09±8.1689.12±9.0354.47±7.5631.21±8.46
6 weeksALT content /(U·L-1)46.24±8.1133.31±8.3436.57±9.1137.69±8.89
BUN content /(mmol·L-1)2.92±1.763.08±1.123.48±1.963.51±1.01
Cr content /(μmol·L-1)61.93±9.0660.95±9.3763.41±8.8658.55±8.29
8 weeksALT content /(U·L-1)39.09±9.0143.42±8.1354.59±8.0255.43±7.93
BUN content /(mmol·L-1)2.88±1.815.32±1.036.09±1.234.36±1.44
Cr content /(μmol·L-1)25.05±8.8545.99±9.1654.47±8.8846.34±9.61
12 weeksALT content /(U·L-1)40.94±8.9745.55±9.017.51±8.1127.35±8.76
BUN content /(mmol·L-1)3.19±1.732.96±1.355.79±1.65.09±1.04
Cr content /(μmol·L-1)25.21±8.1331.22±8.2753.36±9.2334.65±9.62
Tab.3  Clinical biochemistry parameters of rats in different times postoperatively (mean±S.D., = 3)
Fig.3  Photomicrographs of the tissues implanted with surgery thread, CCAM-loaded RT, blank CCAM stained with H&E retrieved at 4 days, surgery thread, CCAM-loaded RT, and blank CCAM retrieved at 1 week (×100).
Fig.4  Photomicrographs of the tissues implanted with surgery thread, CCAM-loaded RT, blank CCAM retrieved at 2 weeks, surgery thread, CCAM-loaded RT, and blank CCAM retrieved at 4 weeks (×100).
Fig.5  Photomicrographs of the tissues implanted with surgery thread, CCAM-loaded RT, blank CCAM retrieved at 8 weeks, surgery thread, CCAM-loaded RT, and blank CCAM retrieved at 12 weeks (×100).
Fig.6  SEM images of implanted CCAM retrieved at 2 weeks postoperatively: blank CCAM; CCAM-loaded RT.
Fig.7  SEM images of implanted CCAM retrieved at 8 weeks postoperatively: blank CCAM; CCAM-loaded RT.
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