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硬葡聚糖的羧甲基衍生物:一种用于药物递送应用的新型热敏水凝胶形成多糖。

Carboxymethyl derivative of scleroglucan: a novel thermosensitive hydrogel forming polysaccharide for drug delivery applications.

作者信息

Feeney Michelle, Casadei Maria Antonietta, Matricardi Pietro

机构信息

Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Rome, Italy.

出版信息

J Mater Sci Mater Med. 2009 May;20(5):1081-7. doi: 10.1007/s10856-008-3665-1. Epub 2009 Jan 10.

Abstract

A carboxymethyl derivative of scleroglucan (Scl-CM) with a derivatization degree of 65 +/- 5% was synthesized. The rheological behaviour of this novel polymer was studied and compared with that of the starting polymer. We observed that the charged moieties carried on the chains could prevent the triple helix formation of Scl. Scl-CM aqueous solutions behave like true polymer solutions up to 1% w/v, whereas above this concentration a weak gel behaviour was observed. CaCl(2) addition to aqueous Scl-CM solutions led to a physical gel formation; the hydrogel strength was related to polymer and CaCl(2) concentrations. Temperature sweeps, registered at 1 Hz on hydrogels differing in CaCl(2) concentration, evidenced a gel --> sol transition in the range of 30-40 degrees C, depending on the molar ratio between carboxylic groups and Ca(+2). In order to verify a possible use of these hydrogels as drug delivery systems, acyclovir was loaded into the network. Rheological analysis evidenced that the loaded drug can affect the hydrogel elastic modulus. The release of acyclovir in phosphate buffer was evaluated at different temperatures in order to assess the suitability of this novel drug delivery system in topical applications.

摘要

合成了一种衍生化程度为65±5%的硬葡聚糖羧甲基衍生物(Scl-CM)。研究了这种新型聚合物的流变行为,并与起始聚合物的流变行为进行了比较。我们观察到,链上携带的带电部分可以阻止Scl形成三螺旋。Scl-CM水溶液在浓度高达1%w/v时表现出真正的聚合物溶液行为,而高于此浓度时则观察到弱凝胶行为。向Scl-CM水溶液中添加CaCl₂会导致形成物理凝胶;水凝胶强度与聚合物和CaCl₂浓度有关。在1Hz下对不同CaCl₂浓度的水凝胶进行温度扫描,结果表明,根据羧基与Ca²⁺之间的摩尔比,在30-40℃范围内会发生凝胶→溶胶转变。为了验证这些水凝胶作为药物递送系统的可能用途,将阿昔洛韦负载到网络中。流变学分析表明,负载的药物会影响水凝胶的弹性模量。在不同温度下评估了阿昔洛韦在磷酸盐缓冲液中的释放情况,以评估这种新型药物递送系统在局部应用中的适用性。

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