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The effect of ingredients commonly used in nasal and inhaled solutions on the secretion of mucus in vitro
International Journal of Pharmaceutics ( IF 5.3 ) Pub Date : 2021-08-28 , DOI: 10.1016/j.ijpharm.2021.121054
Marwa M R R Ayoub 1 , Michael I Lethem 1 , Alison B Lansley 1
Affiliation  

Hypersecretion of mucus is associated with impaired mucociliary clearance that can influence the retention of active pharmaceutical ingredients in the airway but is also linked with recurrent airway disease. Therefore, the effect on mucin secretion of a range of ingredients used in solutions delivered to the nose and lung was studied. Mucin secretion from explants of ovine epithelium was quantified using an enzyme-linked lectin assay (ELLA) or sandwich ELLA depending on the compatibility of the ingredients with the assay. Benzalkonium chloride (0.015% w/w), Methocel™ E50 premium LV (1.0% w/w), propylene glycol (1.5% w/w), potassium sorbate + propylene glycol (0.3% w/w + 1.5% w/w) and polysorbate 80 (0.025% w/w), used at common working concentrations, all increased the secretion of mucin from the explants (P < 0.05). Ethylenediamine tetraacetic acid-disodium salt (EDTA) (0.015% w/w), Avicel® RC591 (1.5% w/w), fluticasone furoate (0.0004% w/w, concentration in solution) and dimethyl sulfoxide (DMSO) (0.2% w/w) did not affect mucin secretion. Compounds increasing mucin secretion could alter the rate of mucociliary clearance and the mucus could provide a barrier to drug absorption. This could predispose patients to disease and affect the activity of delivered drugs, decreasing or increasing their clinical efficacy.



中文翻译:

鼻腔和吸入溶液中常用成分对体外粘液分泌的影响

粘液分泌过多与粘液纤毛清除受损有关,这会影响活性药物成分在气道中的保留,但也与复发性气道疾病有关。因此,研究了递送至鼻和肺的溶液中使用的一系列成分对粘蛋白分泌的影响。取决于成分与测定的相容性,使用酶联凝集素测定 (ELLA) 或夹心 ELLA 对来自绵羊上皮外植体的粘蛋白分泌进行量化。苯扎氯铵 (0.015% w/w)、Methocel™ E50 premium LV (1.0% w/w)、丙二醇 (1.5% w/w)、山梨酸钾 + 丙二醇 (0.3% w/w + 1.5% w/w ) 和聚山梨醇酯 80 (0.025% w/w),在常见的工作浓度下使用,都增加了外植体粘蛋白的分泌 (P < 0.05)。乙二胺四乙酸二钠盐 (EDTA) (0.015% w/w)、Avicel® RC591 (1.5% w/w)、糠酸氟替卡松 (0.0004% w/w, 溶液浓度) 和二甲亚砜 (DMSO) (0.2% w/w) 不影响粘蛋白分泌。增加粘蛋白分泌的化合物可以改变粘液纤毛清除率,并且粘液可以为药物吸收提供障碍。这可能使患者易患疾病并影响所递送药物的活性,从而降低或提高其临床疗效。

更新日期:2021-09-06
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