Mucus-responsive functionalized emulsions: design, synthesis and study of novel branched polymers as functional emulsifiers.
Mucus-responsive functionalized emulsions: design, synthesis and study of novel branched polymers as functional emulsifiers.
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粘液排列在整个身体的潮湿腔体中，通过保护下面的细胞免受外部环境的影响而充当屏障，但它也阻碍药物和药物递送系统的渗透。由于扩散速率较低，因此开发一种可增加粘膜表面保留时间的系统将是有益的。在这里，我们设计了一系列的支化共聚物作为功能性粘液响应性水包油乳化剂，包括亲水性单体低聚（乙二醇）甲基丙烯酸酯和疏水性十二烷基引发剂。该研究的目的是调查成功的乳液形成的链端功能的重要性，通过系统地取代一部分的疏水链端与二级聚（乙二醇）为基础的亲水性引发剂在混合引发策略;减少高达75摩尔%的疏水链端内的支化聚合物乳化剂显示，以保持比较乳液稳定性。这些冗余的链端允许通过含有掩蔽的硫醇基团的基于黄原酸酯的引发剂将官能团并入聚合物中;已知硫醇基团具有粘膜粘附特性，这是由于它们能够与粘液的富含半胱氨酸的区域形成二硫键。在存在生物仿制药粘膜基质的情况下，将由含硫醇的支化共聚物稳定的乳剂的粘膜粘附性质与非功能性乳剂进行比较，并观察到对粘膜表面的粘附增强。重要的是，从先前高度稳定的硫醇官能乳液中观察到液滴破裂和粘液触发的含染料油的释放;这种观察结果没有被非官能乳液反映，其中即使在粘液存在下也保持液滴完整性。粘膜粘附和粘液敏感材料具有许多应用。支化聚合物乳化剂内的冗余链端已经用硫醇官能化，而不损害乳液稳定性，以产生粘液相互作用的乳液。
Mucus lines the moist cavities throughout the body, acting as barrier by protecting the underlying cells against the external environment, but it also hinders the permeation of drugs and drug delivery systems. As the rate of diffusion is low, the development of a system which could increase retention time at the mucosal surface would prove beneficial. Here, we have designed a range of branched copolymers to act as functional mucus-responsive oil-in-water emulsifiers comprising the hydrophilic monomer oligo(ethylene glycol) methacrylate and a hydrophobic dodecyl initiator. The study aimed to investigate the importance of chain end functionality on successful emulsion formation, by systematically replacing a fraction of the hydrophobic chain ends with a secondary poly(ethylene glycol) based hydrophilic initiator in a mixed-initiation strategy; a decrease of up to 75 mole percent of hydrophobic chain ends within the branched polymer emulsifiers was shown to maintain comparative emulsion stability. These redundant chain ends allowed for functionality to be incorporated into the polymers via a xanthate based initiator containing a masked thiol group; thiol groups are known to have mucoadhesive character, due to their ability to form disulfide bonds with the cysteine rich areas of mucus. The mucoadhesive nature of emulsions stabilised by thiol-containing branched copolymers was compared to non-functional emulsions in the presence of a biosimilar mucosal substrate and enhanced adherence to the mucosal surface was observed. Importantly, droplet rupture and mucus triggered release of dye-containing oil was seen from previously highly-stable thiol-functional emulsions; this observation was not mirrored by non-functional emulsions where droplet integrity was maintained even in the presence of mucus. Mucoadhesion and mucus-sensitive materials have many applications. Redundant chain-ends within branched polymer emulsifiers have been functionalized with thiols, without compromising emulsion stability, to create mucus-interacting emulsions.
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影响因子：
3.9
作者：
Hobson, James J.;Edwards, Stephanie;Rannard, Steve P.
通讯作者：
Rannard, Steve P.
DOI：
10.1152/ajpgi.2001.280.5.g922
发表时间：
2001-05-01
影响因子：
4.5
作者：
Atuma, C;Strugala, V;Holm, L
通讯作者：
Holm, L
影响因子：
4.7
作者：
Dufresne, MH;Gauthier, MA;Leroux, JC
通讯作者：
Leroux, JC
影响因子：
4.6
作者：
Hung Thanh Lam;Leonaviciute, Gintare;Bernkop-Schnurch, Andreas
通讯作者：
Bernkop-Schnurch, Andreas
影响因子：
--
作者：
Graham, Susan;Rannard, Steve P.;Sherrington, David C.
通讯作者：
Sherrington, David C.