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目的:考察相对分子质量(Mr)及取代度对寡聚精氨酸壳聚糖(CS-R9)体外透皮吸收作用的影响。方法:分别以低、中、高Mr的壳聚糖(LCS、MCS、HCS)为原料,合成具有相近取代度的LCS-R9、MCS-R9、HCS-R9;以LCS为原料,通过改变CS与R9的摩尔比,合成具有不同取代度的LCS-R9-1、LCS-R9-2、LCS-R9-3;以替硝唑(TNZ)为模型药物,采用Franz扩散池法,考察各种CSR9的体外透皮促进作用。结果:经过FTIR、1H-NMR的图谱分析,可以确定本实验所合成的LCS-R9-1、MCS-R9、HCS-R9、LCSR9-2、LCS-R9-3的取代度分别为2.30,2.17,2.20,8.05,15.87;与空白组、氮酮组、LCS组、R9组、LCS+R9组等对照组相比,LCSR9-1对TNZ有明显的透皮促进作用(P<0.05);当取代度相似,CS的Mr不同时,12 h之内,LCS-R9-1与HCS-R9的促进作用相似,均明显大于MCS-R9(P<0.05);12-24 h,HCS-R9的作用有下降趋势,但与LCS-R9-1比较,差异无统计学意义(P>0.05);当CS的Mr相同,而取代度不同时,21 h内,促进作用随着取代度的增加而增加,之后,则呈相反趋势。结论:Mr及取代度对CS-R9的透皮吸收促进作用有较大影响,值得进一步研究其体内作用规律及相关机制。
Objective: To investigate the effect of relative molecular mass (Mr) and degree of substitution on percutaneous absorption of oligoarginine chitosan (CS-R9) in vitro. Methods: LCS-R9, MCS-R9 and HCS-R9 with similar degree of substitution were synthesized by using low, medium and high Mr Chitosan (LCS, MCS and HCS) as raw materials. LCS-R9-2, LCS-R9-3 with different degrees of substitution were synthesized by the molar ratio of RZ to R9. The Franz diffusion cell method was used to model the drug of TNZ, CSR9 in vitro transdermal promoting effect. Results: The FTIR and 1H-NMR spectra showed that the substitutions of LCS-R9-1, MCS-R9, HCS-R9, LCSR9-2 and LCS-R9-3 synthesized in this experiment were 2.30, 2.17 , 2.20,8.05 and 15.87, respectively. LCSR9-1 had a significant transdermal promoting effect on TNZ compared with blank group, azone group, LCS group, R9 group and LCS + R9 group (P <0.05) The effect of LCS-R9-1 on HCS-R9 was similar to that of MCS-R9 (P <0.05) within 12 h, while at 12-24 h, (P> 0.05). When the Mr of CS was the same and the degree of substitution was different, within 21 h, the promotion effect with the increase of the degree of substitution Increase, then, the opposite trend. Conclusion: Mr and degree of substitution have a significant effect on the promotion of percutaneous absorption of CS-R9, and it is worth further studying the mechanism of action and related mechanisms in vivo.