| Biodegradable material load of antibiotics used in clinical treatment for inflammation has been more common, such as hydroxyapatite, poly(sebacic anhydride), polylactic acid and their copolymer with glycolic acid, etc. The greatest advantage of the biodegradable materials is that it can degraded completely in the body at the end of the drug release process. What’s more, this system can obtain high concentration of antibiotics at the infection site, which also can overcome the drawbacks of secondary surgery for the traditional undegrabable carriers.Poly(sebacic anhydride) and polylactic acid were blend with different ratio, as the release carriers for ofloxacin in the treatment of bone infection has been investigated in our previous work. The result of the study revealed that blengding them together in the release, combination of the advangtage of the two polymers was obtained. The contolled release system showd a release behavior close to zero order relase with weight ratio of1:9. And "burst effect" wasn’t observed with a long release time for the1:9system. In the later study, more effective anbiotics levofloxacin was used to investigate the effect of ratio (drug and the polymer carrier). Till now, the effect of the molecular weight to controlled release system still remain unknow, especially the sturcutre, physical and chemical properties.Therefore, a series of poly(sebacic anhydride) with molecular weight gradient were prepared to investigate the issue mentioned above. Then poly(sebacic anhydride) and polylactic acid blend was prepared by solvent volatilizing method and characterized by various techniques such as Infrared spectrometry, X-ray powder diffraction, gel permeation chromatography, differential scanning calorimetry and scanning electron microscopy. After that, drug load system consist of levofloxacin and the blend was used for controlled release and bacteriostat study in vitro. The effect of poly(sebacic anhydride) molecular weight to the drug load system was emphatic discussed, which will provide basis for the chosen of these polymer carrier.Part1Structure analysis of poly(sebacic anhydride)(PSA) and poly lactic acid (PLA) blendObjective:To investigate the easibility and necessity of controlled release system consist of PSA/PLA matrix, series of poly(sebacic anhydride) with molecular weight gradient were prepared. PSA/PLA carriers was characterized by various techniques to afford theory evidence to select or further improve the belnding carriers.Methods:Poly(sebacic anhydride) with different weight molecular and polylactic acid blend was prepared by solvent volatilizing method and characterized by various techniques such as infrared spectrometry (IR), X-ray powder diffraction (XRD), gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM).Results:Different molecular weight PSA was synthesized through melt condensation polymerization by changing the reaction time and temperature. High yield PSA was obtained at this condition, which is benefit for industrialization. The FT-IR study revealed the existence of-OH,-CH3,-CH2, C=O and C-O, which indicated the successful synthesis of PSA. X-ray diffraction demonstrated that PSA made here is semicrystalline polymer, and the PLA is a crystalline one. The result of GPC showed low distribution index of the prepared PSA, which will in favor for the compatibility of the two polymer. The DSC results shown Tg and Tm of the blend matrix dramatically influenced by the molecular weight of PSA. The Tm of PSA-5000/PLA and PSA-13000/PLA increased to146℃and150℃, respectively. The Tm of the PSA/PLA matrices increased slightly with increase in PSA molecular weight. The SEM result revealed that the PSA-5000/PLA/LOF composites displayed a porous structure and rough external surfaces. The PSA-13000/PLA/LOF composites showed a dense structure and smooth external surface.Conclusion:Firstly, through the combination with high crystalline PLA, the crystallinity of PSA was dramatically improved. What’s more, the stability of the matrix was improved, consequently the release time was extended. Secondly, the release rate can be controlled by the molecular weight of the PSA in the matrix, so carriers with different release rate can be chosen by the molecular weight of PSA. Part ⅡLevofloxacin loading polylactic acid/poly(sebacic anhydride) tablets in vitro release and bacteriostasis experimentObjective:According to the results of the structure analysis, levofloxacin loading PSA/PLA pills was used in the drug release and bacteriostasis investigation. Efforts had been made to find an ideal system of treatment and prevent for bone infection.Methods:Beads containing different molecular weight were respectively put into0.1M phosphate buffer (pH=7.4) in a test tube which under homoeothermic water bath at37℃. The buffer was regularly replaced at different time point within38days of the test. The levofloxacin concentration in the buffer was measured with UV-vis spectroscopy at287nm.Then pills containing PSA with relative high molecular weight (Mw=13000) was used as levofloxacin carrier for the test of bacteriostasis. The bacteriostasis experiment was conducted in staphylococcus aureus, escherichia coli and pseudomonas aeruginosa media within three months. The diameter of the inhibition zone was measured timingly.Results:Among the drug loading system with different molecular weight (Mw=5000,7000,9000,11000,13000), the bead containing PSA(Mw=5000) showed obvious burst effect and the effecttive drug release amount exceeding90%. Interestingly, as the increase of the molecular weight, the burst effect and effective drug release amount decreased obviously. The daily drug release concentration of bead containing PSA(Mw=13000) maintained at10-60μg/ml within38days, which exhibits a nearly perfect linear release behavior. The drug release concentration of other release system changed at a wide range. The results of in vitro release indicates that carrier containing PSA(Mw=5000) exhibits obvious burst effect with a fast release rate, which can be used as the treatment drug carrier. The carrier containing PSA(Mw=13000) exhibits stable release rate, which can be used as the prevent drug carrier. The is consistent with results of the structure analysis. The current results indicated that blending PLA and PSA with dfferent molecular weight to act as drug carrier could be a potentially effective method for local drug release.The bacteriostasis test results showed that the beads containing PSA(Mw=13000) produced inhibition zone of bacteria to staphylococcus aureus, escherichia coli and pseudomonas aeruginosa within96days. The diameters of the inhibition zone of bacteria were33.4±3.7mm,40.4±3.4mm and37.2±2.6mm, respectively. The most intense inhibition effect was occurred at the first day for all bacteria, after that the size of inhibition zone tended to steady.Conclusion:Firstly, the release rate of levofloxacin from the carrier can be controlled by the molecular weight of the poly(sebacic anhydride). Secondly, the carrier containing PSA (Mw=13000) can be used as the prevent drug carrier for the condition of no obvious infection wound. The carrier containing PSA (Mw=5000) is more suitable for the condition of open fractures with infection. |
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