从白桑树根皮中提取的用于吸入给药的抗感染桑根元的生物制药分析

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY International Journal of Pharmaceutics: X Pub Date : 2024-08-05 DOI:10.1016/j.ijpx.2024.100272
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摘要

从桑树根皮中分离出的桑树 Diels-Alder 型加合物(MDAAs)具有抗病毒和细菌病原体的双重活性,但口服后的疗效令人担忧。吸入给药可克服口服生物利用度的问题,提高治疗呼吸道感染的疗效。为了评估 MDAA 吸入给药的适宜性,我们对两种具有生物活性的 MDAA 立体异构体桑根翁 C(SGC)和桑根翁 D(SGD)作为分离天然化合物和母体提取物(MA21、MA60)的物理化学(如 pH 值、pKa、logP、pH 值依赖性溶解度)和生物制药(上皮细胞毒性、渗透性和吸收)特性进行了评估。尽管结构相似,但在 pH 值为 1.2-7.4 的范围内,SGD 的溶解度比 SGC 高 10 倍,在中性 pH 值时略有增加。与母体提取物相比,这两种化合物在分离状态下的溶解度更高。与 SGD 相比,亲脂性更强的 SGC 具有更强的细胞毒性,这表明其具有更好的细胞渗透性,摄取研究也证实了这一点。不过,SGC 和 SGD 在完整的 Calu-3 单层细胞中没有表现出可测量的渗透性,这突出表明它们有可能在吸入给药后增加肺部滞留并提高局部抗感染活性。研究结果表明,分离形式而非提取物形式的 SGC 和 SGD 有希望成为治疗肺部感染的肺部给药候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Biopharmaceutical profiling of anti-infective sanggenons from Morus alba root bark for inhalation administration

Mulberry Diels-Alder-type adducts (MDAAs), isolated from Morus alba root bark, exhibit dual activity against viral and bacterial pathogens but show sobering efficacy following oral administration. Inhalation administration may overcome issues with oral bioavailability and improve efficacy for the treatment of respiratory infections. To assess the suitability of MDAAs for inhalation administration, physicochemical (e.g. pH, pKa, logP, pH-dependent solubility) and biopharmaceutical (epithelial cytotoxicity, permeability, and uptake) properties of two bioactive MDAA stereoisomers sanggenon C (SGC) and sanggenon D (SGD) were evaluated as isolated natural compounds and within parent extracts (MA21, MA60). Despite their structural similarity, SGD exhibited a 10-fold higher solubility than SGC across pH 1.2–7.4, with slight increases at neutral pH. Both compounds were more soluble in isolated form than in the parent extracts. The more lipophilic SGC was found to be more cytotoxic when compared to SGD, indicating a better cellular penetration, which was confirmed by uptake studies. Nonetheless, SGC and SGD exhibited no measurable permeability across intact Calu-3 monolayers, highlighting their potential for increased lung retention and improved local anti-infective activity following inhalation administration. Results suggest that SGC and SGD in isolated form, rather than as extracts, are promising candidates for pulmonary drug delivery to treat lung infections.

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来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
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