| Biomaterial centered infections (BCI) represent a more and more significantchallenge to the medical community with the more widespread application of medicalimplants. How to eliminate BCI becomes the urgent task in the Clinical Applicationsof Biomaterials at present due to its high incidence and poor treatment.In recent years, Antimicrobial drug delivery systems based on biocompatiblepolymers becomes the research hot spot. Although these drug delivery systems havesome certain advantages, most of them used methods of bonding the drugs withpolymers via a physical blend not chemical copolymerization process, which makesthem can’t release in a controlled way and eliminate BCI safely and effectively.Through Molecular Design and Polymer Fabrication，the foreign studiers synthesizedpolymer prodrug by incorporating antimicrobial drugs covalently with copolymer.The polymer prodrugs have no pharmacological activities itself and released the drugunder specified condition in a controlled way, such as temperature, PH, enzymecatalysis and so on, which make them releasing drugs with good pharmacologicaleffects with right number, at right time in accordance with the inflammatory response.The polymer prodrug is a kind of intelligent andcontrolled intravitreous delay releasesystem, which not only can avoid drug relase to a excessive amount, but also canresist inflection in a long-term way.Based on the preparation and characterization of controlled release antibacterialmaterial—ciprofloxacin-polyurethanes (CFPU) which were prepared successfullythrough Molecular Design and Polymer Fabrication, that is to incorporateciprofloxacin—a fluoroquinolone antibiotic covalently into the backbone of apolyurethane copolymer with hexane diisocyanate and polycaprolactone.What we didare following:In the first part, the methed of HPLC is established to investigate the drug-releaseregularation of the polymeric prodrug of ciprofloxacin (CFPU) which is prepared inthe former paper, by placing it in cholesterol esterase (CE) or in PBS. The analytical column used was Ultimate AQ-C18(particle size5μm,250mm×4.6mm) at30℃.CFPU was analyzed for drug content and drug release by HPLC using mobile phaseconsisting of HPLC grade water (0.05%trifluoroacetic acid): HPLC grade methanol(72∶28, v/v) at flow rate of1.0ml/min. Detector wavelength was set at279nm.Andthe results showed that the HPLC method is accurate, reliable and simple. Thedrug-release of CFPU was bioresponsive and could be accorded with first orderkinetics. It was observed that CF was released from CFPU by a combination ofdiffusion and erosion mechanism, mainly in the manner of diffusion. Antiseptic drugciprofloxacin can be released from CFPU slowly and be in response to CE to someextent in an controlled manner.In the second part, The broth microdilution method was performed to determinedthe minimal inhibitory concentration of CFPU to Staphylococcus aureus andEscherichia coli. Paper-disc method (agar diffusion bioassay) was use to assess theantibacterial activity to Staphylococcus aureus and Escherichia coli. The resultsshowed that The CFPU degradation can inhibit the growing of Staphylococcus aureusand Escherichia coli, with the minimal inhibitory concent to Staphylococcus aureus0.296037mg/L, to Escherichia coli0.592073mg/L.In the third part, Through cell culture of human embryonic kidney cell293A and rataortic smooth muscle cell A7r5, MTT method was introduced to evaluate thecytotoxicity of CFPU degradation in vitro. The results showed that the relative growthrates(RGR) were bettween75%~99%and all groups were the first cytoxicity gradewhich illustrated that CFPU have good biocompatibility. |
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