Thiomers: Impact of in situ cross-linkers on mucoadhesive properties
Thiomers: Impact of in situ cross-linkers on mucoadhesive properties
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DOI：
10.1016/j.ejps.2017.05.051
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发表时间：
2017-08-30
影响因子：
4.6
通讯作者：
Bernkop-Schnurch, Andreas
中科院分区：
文献类型：
--
作者：
Hung Thanh Lam;Leonaviciute, Gintare;Bernkop-Schnurch, Andreas
本研究的目的是评估原位交联剂对硫代聚物的胶凝和粘膜粘附特性的影响。聚卡波非-半胱氨酸偶联物（PCP-cys）是由聚卡波非与L-半胱氨酸通过1-乙基-3-甲基-1，2-二氢呋喃（1-ethyl-3-methyl-1，2-dihydroxy（3-二甲基氨基丙基）碳二亚胺盐酸盐（EDAC）和N-羟基琥珀酰亚胺（NHS），而原位交联剂以2-（（2-氨基-2-羧乙基）二硫烷基）烟酸（cys-MNA）为配体，通过与分子量为2.1-、6-和15 kDa的聚丙烯酸（PAA）形成相同的键，合成了聚丙烯酸-cys-MNA（PAA-cys-MNA）。通过测定PCP-cys和PAA-cys-MNA与纯化猪肠粘液混合物的动态粘度和旋转圆筒法研究了PCP-cys和PAA-cys-MNA的原位交联性能。采用旋转管技术研究了聚合物在纯化猪肠粘液中的扩散。结果表明，原位交联剂（PAA 2.1-，6-，1510 a）增加PCP-cys/粘液混合物的动态粘度的5.1-，5.6-，和3.5倍。与单独的PCP-cys相比，10%的原位交联剂PAA 2.1-、6-或15 kDa和90%的PCP-cys的组合分别使粘附时间增加1.1-、2.0-和4.9倍。扩散研究表明，低分子量PAM高度渗透到粘液凝胶层，由于其高聚合物链的流动性相比，PCP-cys。结果为原位交联剂作为胶凝和粘膜粘附增强剂的潜力提供了证据。
The aim of this study was to evaluate the impact of in situ cross-linkers on the gelling and mucoadhesive properties of thiomers. Polycarbophil-cysteine conjugate (PCP-cys) was synthesized by covalent attachment of Lcysteine to polycarbophil via amide bond formation mediated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) and N-hydroxysuccinimide (NHS) whereas in situ cross -linkers (PAA-cys-MNA) were synthesized by the same bond formation between poly(acrylic acid) (PAA) of 2.1-, 6-, and 15 kDa and 2-((2amino-2-carboxyethyl)disulfanyl)nicotinic acid (cys-MNA) used as ligand. The in situ cross -linking properties were studied via rheological measurements of dynamic viscosity of mixtures of PCP-cys and PAA-cys-MNA with purified porcine intestinal mucus and via rotating cylinder method. The diffusion of polymers in purified porcine intestinal mucus was studied via rotating tube technique. The results showed that in situ cross-linkers (PAA 2.1-, 6-, 1510a) increase the dynamic viscosity of PCP-cys/mucus mixtures by 5.1-, 5.6-, and 3.5-fold. Combinations of 10% of in situ cross-linkers PAA 2.1-, 6- or 15 kDa and 90% PCP-cys increased the adhesion time 1.1-, 2.0- and 4.9-fold, respectively, compared to PCP-cys alone. Diffusion study showed that low molecular mass PAM highly penetrate into the mucus gel layer due to their high polymer chain mobility compared to PCP-cys. The results provide evidence for the potential of in situ cross-linking agents as gelling and mucoadhesion enhancers.