| Periodontal diseases which occur at support organization in the teeth (periodontal tissue) are bacterial infections caused by biofilm matures and other Multi-factors. Iodine is an excellent and rapid non-specific broad-spectrum fungicides against pathogenic bacterium of periodontitis, such as Gram-negative bacterias. A new drug delivery system including iodine as the model drug, crosslinked water-soluble-starch microspheres as drug carrier and with hydrophilic ointment matrix, was designed in the study for the treatment of periodontitis.An inverse suspension polymerization method was utilized to synthesize crosslinked water-soluble-starch microspheres, and it preparation proccess was optimized though single factors, and orthogonal experiments in which factors influencing emulsification and cross-linkd reaction. When the starch-alkali aqueous ratio was 7:20:(g:g), the amount of aqueous phase was 20 g, the amount of oil phase was 160 mL, the weight of emulsifier was 8 g and the stirring rate was 400 rpm, fine emulsion was gained after 20 min stirring. Then crosslinker was added under 45℃, and the reaction continued 4h. The microspheres with the diameter around 67±16μm, a narrow particle size distribution (PSD) and good spherical shape were gained.Fourier-transformed infrared spectrometry, SEM, laser particle size analyses, differential scanning calorimetry and thermo-gravimetry were employed to characterize the structure and properties of the starch microshperes. The results proved that the structure and characteristics of the water-soluble-starch changed dramatically after crosslinked. The existence of abundant hydroxyls groups ensured the hydrophilicity and good water absorbtion ability and drug absorption microspheres which can be used as drug-loader for iodine.Then influences of the particle size of the microspheres, concentration of iodine solution, the swelling ability of microspheres, time of adsorbtion drug, the temperature of adsorbtion on adsorption ability for iodine of crosslinked water-soluble-starch microspheres were studied.The results showed that crosslinked water-soluble-starch microspheres had a good performance on the sensitivity of drugs and drug absorbtion.Adsorption of microspheres had good correlation with microspheres’absorption degree and swelling ratio. Correlation coefficient were 0.914 and 0.894. We could change the adsorption amount of microspheres by changing the concentration of drug solution swelling capacity of microspheres and the time for absorbtion drug.Adsorbing method was employed to load iodine into blank crosslinked water-soluble-starch microspheres. Orthogonal experiments were utilized to optimize the conditions for preparing the water-soluble-starch microspheres containing 4.8±0.3%. Stability study was carried out at 40℃and 60℃for 12h, and the loss of iodine in the microspheres was not detected. The results showed that crosslinked water-soluble-starch microspheres could be used as drug-loader for iodine and avoid the volatilization of idione from liquid formulation.Admixture of PEG400 and Poloxamer188 was used as base to prepare iodine crosslinked water-soluble-starch microspheres ointment. The extruding ability and the release pattern of iodine in vitro of different formulas were studied. The formula, that consisted of 2.26g of PEG400,0.8 g of Poloxamer188, and 2 g of crosslinked water-soluble-starch microspheres containing 5% iodine were finally selected. The quality assessment of ointment showed that it had good stability.Experimental periodontitis model of rats that imitated clinical pathological characteristics was established. The result of pharmacodynamics study between iodine crosslinked water-soluble-starch ointment and positive drug show that both of them could reduce the cilinical indexes of periodontal disease (BOP, GI, DPP and Pathological inflammatory)significantly. The irritation test of rabbits showed that iodine crosslinked water-soluble-starch ointment was safe to apply on mucosa. It was indicated that the iodine crosslinked water-soluble-starch ointment was an good slow-release drug delivery system periodontitis therapy. |
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