Preparation Technology And Biomedical Characteristics Of Implantable Absorbable Sustained Releasing Carboxymethyl Chitosan Microspheres

In the prevention and treatment for local infection, conventional oral and venous administraton of antibiotic have lots of limits, such as low and instable blood concentration, side effects as well. At present, local admistration of antibiotics has low efficiency; the carrier is not be easily degraded and need to be taken out secondly. In our study, we aimed to explore a new kind of implantable drug delivery system (IDDS) , which has better effect, lower prevention for tissue repiring, better biodegradability and biocompatibility.We adopt microspheres (MS ) as drug form according to the drug efficency of antibiotics and the biodegradability and biocompatibity and lower tissue repare prevention of the carrier, and chose the carboxymethyl chitosan (CMC) as sustained releasing excipient, ciprofloxacin Hydrochloride (CPX) as loaded antibiotics. The emulsification and cross-link was chosed as preparation process according to the characteristics of the carrier and excipient. The formular was choosen throuth orthogonal design acccoding to the MS' apparent characteristics. Then we detected the physiochemical characteristics of the MS sample through scanning electron microscopy ( SEM ) , infrared spectrum ( IR )and differential thermal analysis ( DTA ) . We detected the releasing characteristics of sample and its influencing factors. And the formular was optimized according the detected results.We probe the purifyication technique of blood and tussue fluid and used the method of high performance liquid chromatography (HPLC ) to examine the blood and tissue fluid concentratein of CPX. The CMC/CPXMS samples was prepared according to the optimized formular and preparation processs. We implanted the prepared sample into animal model and detected biocharicteristics such as biodegradability and biocompatibity through general observation, pathology examination and transmission electron microscopy (TFM ) et al. At the same time, we detected in vivo the drug concentrateion and diversification in blood and tissue fluid of animal model and definituded the drug releaseing pattern in vivo.We got the optimized formular as The ratio of CMC's concentration to CPX's to NaCl's was 2 to 1 to 1; The cubage of water phase to oil phase's in the system ofemulsification was 1 to 4. The temperature of emulsification was 5 to 8 ; The degree of cross-linking impressed by the content ratio of glutaraldehyde ( GD ) to CMC was 1 to 1 . The cross-linking should last for three hour. The rate of emulsificational stiring was 800 rpm. The MS prepared according to these standards was well proportioned and with microbores basing diameter about lum~3um. The diameter of the prepared MS was averagly about 200um; the content of CPX in these MS was about 17.5%. These MS had outstanding hydrophilic capability and would turn into gelatin after swelling. The swelling ratio was 65%. Through IR and DTA examination, it was confirmmed that the CPX and CMC distributed amorphismly in the MS. The releasing test suggested the CPX could last for 7 days and had no phenomena of "sudden release". The accumulative releasing ratio had positive correlation with the square root of time. The releasing behavior could be simulated by the Higuchi equation. In vivo after the MS was implanted into animal model we detected through general observation, pathology examination and TEM and found that it had good biocompatibility, and littlee inflammatory responses were found. The MS could be degraded by lysosome through "swallow"after being degraded into segment throngh lysozyme. The releasing test in vivo indicated that the concentration of CPX in the local tissue could last for 10 days above MICgo of Mlicrococcus aureus. The "sudden release" was not found. The maxium concentration was gained 24 hour after implanted. But the concentration validity could achieve half an hour after implant. The releasing rate had negative correlation with time after the point of the maxium concentration.We recommended that CMC is an ideal kind of biodegradable biomaterial possessing functi...