海藻酸钠疏水改性及负载大黄素体外缓释研究

In Vitro Study of Hydrophobically Modified Sodium Alginate and Loaded Emodin for Sustained Release

目的通过末端封装氨基的聚乳酸(PLA-NH_(2))对海藻酸钠进行疏水改性,提高疏水性药物大黄素的负载量并增强其缓释性能。方法采用1-(3-二甲氨基丙基)-3-3乙基碳二亚胺盐酸盐(EDC·HCl)与N-羟基琥珀酰亚胺(NHS)形成的催化体系来活化海藻酸钠中的羧基,与PLA-NH_(2)发生酰胺化反应实现疏水性聚乳酸的接枝。通过改变海藻酸钠与末端PLA-NH_(2)的投料比,实现疏水性调节,并将疏水改性后的海藻酸钠与大黄素制备成微球进行体外释放研究。结果红外表征结果表明海藻酸钠与氨基化聚乳酸成功缩合,成功实现了海藻酸钠的疏水改性。摩尔比为(COOH/NH_(2))24改性的样品大黄素负载率21.2%,高于单纯的海藻酸盐11.4%,改性后的样品36h释药率较单纯海藻酸盐由91.2%降低至85.3%,具有明显的缓释效果。结论海藻酸钠中羧基进行酰胺化反应可以很好的实现对海藻酸钠的接枝改性。PLA-NH_(2)疏水改性后的海藻酸钠聚合物显著提高了疏水性药物大黄素的负载量并增强其体外缓释性能。

Objective To increase the loading capacity of the hydrophobic drug emodin and enhance its sustained-release properties,sodium alginate was hydrophobically modified by polylactic acid(PLA-NH_(2))encapsulated with amino groups at the end.Methods Activation of sodium alginate by a catalytic system of 1-(3-dimethylaminopropyl)-3-3-ethylcarbodiimide hydrochloride(EDC·HCl)and N-hydroxysuccinimide(NHS)in the carboxyl group.The hydrophobic polylactic acid was grafted by amidation reaction between EDC·HCl and PLA-NH_(2).The hydrophobicity was adjusted by changing the feeding ratio of sodium alginate to terminal PLA-NH_(2),and the hydrophobically modified sodium alginate and emodin were prepared into microspheres for in vitro release studies.Results Infrared characterization results showed sodium alginate was successfully condensed with aminated polylactic acid,and the hydrophobic modification of sodium alginate was achieved.The emodin loading rate of the modified sample with a molar ratio of(COOH/NH_(2))24 was 21.2%,which was higher than that of the pure alginate,which was 11.4%.The 36h drug release rate of the modified sample was lower than that of the pure alginate from 91.2%to 85.3%with an obvious sustained release effect.Conclusion The amidation reaction of the carboxyl group in sodium alginate could implement the graft modification of sodium alginate.The hydrophobically modified sodium alginate polymer of PLA-NH_(2)significantly increased the loading capacity of the hydrophobic drug emodin and enhanced its sustained release performance in vitro.