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Mucus-responsive functionalized emulsions: design, synthesis and study of novel branched polymers as functional emulsifiers

机译：粘液响应官能化乳液：新型支链聚合物的设计，合成和研究作为功能性乳化剂

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摘要

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 polymersviaa 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.
机译：粘液在整个身体中排出潮湿的空腔，通过保护潜在的细胞免受外部环境来抵抗潜在的屏障，但也阻碍了药物和药物递送系统的渗透。随着扩散速率低，可以在粘膜表面上增加保留时间的系统的发展将证明是有益的。在此，我们设计了一系列支化共聚物，以充当包含亲水性单体寡核苷酸（乙二醇）甲基丙烯酸酯和疏水十二烷基引发剂的功能粘液响应物的水包油乳化剂。该研究旨在探讨链末功能对成功乳液形成的重要性，通过系统地替代疏水链末端以仲聚（乙二醇）的亲水性引发剂在混合引发策略中;表示支化聚合物乳化剂内最多75摩尔百分之一的疏水链末端，以保持对比乳液稳定性。这些冗余链末端允许掺入含有掩蔽硫醇组的基于聚合物血清酸盐的引发剂中的功能;巯基已知有粘膜粘附特性​​，由于其形成黏液富含半胱氨酸区二硫键的能力。将含硫醇的支链共聚物稳定的乳液的粘膜粘附性与在生物仿生粘膜基质存在下的非官能乳液中，并观察到对粘膜表面的增强粘附。重要的是，微滴破裂和含染料的油的粘液触发的释放从先前高度稳定的硫醇官能乳液看出;这种观察结果未被非功能性乳液镜像，即使在粘液存在下也保持液滴完整性。

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  • 来源
    《RSC Advances》 |2020年第51期|共13页
  • 作者

    Edwards Stephanie E.; Flynn Sean; Hobson James J.; Chambon Pierre; Cauldbeck Helen; Rannard Steve P.;

  • 作者单位

    Univ Liverpool Dept Chem Crown St Liverpool L69 7ZD Merseyside England;

    Univ Liverpool Dept Chem Crown St Liverpool L69 7ZD Merseyside England;

    Univ Liverpool Dept Chem Crown St Liverpool L69 7ZD Merseyside England;

    Univ Liverpool Dept Chem Crown St Liverpool L69 7ZD Merseyside England;

    Univ Liverpool Dept Chem Crown St Liverpool L69 7ZD Merseyside England;

    Univ Liverpool Dept Chem Crown St Liverpool L69 7ZD Merseyside England;

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  • 正文语种 eng
  • 中图分类 化学;
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