Preparation of Carboxymethyl-chitin Nanoparticles by Covalent Crosslinking and Their In Vitro Evaluation

H. Onishi, K. Kume, Ken-ichi Koyama, Y. Machida
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Abstract

The degree of deacetylation and molecular weight of carboxymethyl-chitin (CM) were manipulated using 10% (w/v) NaOH aqueous solution at 25˚C and 5 M HCl aqueous solution at 40˚C, respectively. The resultant CMs were char- acterized by 1 H-NMR spectroscopy and size exclusion chromatography/multi-angle light scattering. The degree of deace- tylation of 7 - 35% (mol/mol) and molecular weight of 43,000 - 449,000 were achieved. Nanoparticles were prepared us- ing W/O emulsification and amide coupling. Nanoparticles with the size of less than 400 nm were obtained using CM with a high degree of deacetylation and low molecular weight, CM48-L. When the mixture of CM-mitomycin C conjugate and CM48-L underwent W/O emulsification and amide coupling, nanoparticles with the size of ca. 350 nm were obtained, and released mitomycin C fairly fast but gradually. CM with a high degree of deacetylation and low molecular weight was suggested to be useful for the production of CM nanoparticles.
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共价交联法制备羧甲基甲壳素纳米颗粒及其体外评价
采用10% (w/v) NaOH水溶液(25˚C)和5 M HCl水溶液(40˚C)对羧甲基几丁质(CM)的脱乙酰度和分子量进行了测定。用1h - nmr光谱和粒径排除色谱/多角度光散射对合成的CMs进行了表征。结果表明,甲基化度为7 ~ 35% (mol/mol),分子量为43000 ~ 449000。采用W/O乳化和酰胺偶联法制备纳米颗粒。采用高脱乙酰度、低分子量的CM (CM48-L)制备了尺寸小于400 nm的纳米颗粒。cm -丝裂霉素C偶联物与CM48-L的混合物经W/O乳化和酰胺偶联后,可获得约350 nm大小的纳米颗粒,该纳米颗粒释放丝裂霉素C的速度较快,但速度缓慢。高脱乙酰度和低分子量的CM被认为是生产CM纳米颗粒的有用材料。
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