Preparation And Characterization Of Antibacterial Drug System For The Treatment Of Osteomyelitis

Osteomyelitis is a refractory disease in clinical which is mainly caused by the infection of Staphylococcus aureus(SA). To overcome the shortcomings of traditional therapy for osteomyelitis, we designed two systems based on the drug delivery strategy, one was the targeted nano drug delivery system and the other one was temperaturesensitive hydrogel drug delivery system. Vancomycin was used as the model drug which is able to kill SA effectively.For targeted nano-drug delivery system, we chose alendronate(ALN) as the target molecule because of the specific adsorption of ALN to inorganic substance hydroxyapatite(HA) which is the main component of bone. We prepared copolymer PLGA-PEG-COOH by ring-opening polymerization reaction, and then ALN was grafted to the surface of micelles which was self-assembled from the prepared copolymer. Nuclear magnetic resonance(1H-NMR), dynamic light scattering(DLS), transmission electron microscopy(TEM) were used to characterize the structure of the copolymer and the particle size, surface morphology of the micelle. After that, the release behavior, cell biocompatibility, HA adsorption and antibacterial properties were also be studied.Drug release study showed that the nano-drug delivery system we have prepared has the effect of sustained release of drug. The synthetic material was co-cultured with BMSCs and L02 cell, MTT assay showed that the material has good biocompatibility. HA adsorption results showed that the nano micelle can be effectively adsorbed on the surface of HA, while drug-loaded micelle can effectively inhibit the growth of SA. From the results above, we can conclude that, the bone-targeted PLGA-PEG-ALN nano drug delivery system which was prepared in this study has a wide prospect in the delivery of vancomycin for targeted therapy of osteomyelitis.For temperature-sensitive hydrogel drug delivery system, we synthesized PLGAPEG-PLGA by ring-opening polymerization which has good biocompatibility and biodegradability. By altering the length of the hydrophobic block, we obtained hydrogels with different phase transition temperatures. The mechanism of the phase transition of the hydrogel was studied. At low temperature, copolymer exists in the solution in the form of free micelles, and as the temperature rises, micelles adhere with each other, the over growth of adhesive micelle leads to the formation of the final gel. If temperature rises further, micelle will be precipitated from the solution because of the greatly increased hydrophobicity. With the growth of the hydrophobic block or the increase of the copolymer concentration, the temperature of phase transition from solution to gel is reduced.At low temperature, encapsulation process was completed by directly dissolving vancomycin in the polymer solution. Hydrogel was formed at 37 ?and the drug encapsulation efficiency was 100%. It has the property of sustained drug release, and the release rate was higher in acidic environment. MTT assay showed that the prepared material has good biocompatibility to BMSCs, thus the prepared hydrogel solution can be injected into the site of osteomyelitis. After encapsulation of vancomycin, hydrogel showed bactericidal effect as good as pure vancomycin. Based on the above points, the temperature-sensitive hydrogel prepared in this study can be injected into skeletal sites, and has great potential for the application in the topical treatment of osteomyelitis which is caused by SA.Therefore, the bone-targeted nano system and injectable thermo-sensitive hydrogel system prepared in this study are of great value and provide important reference for the future application of drug delivery system in the clinical treatment of osteomyelitis.