Mirko Marino , Claudio Gardana , Antonio Scialpi , Giuseppe Giorgini , Paolo Simonetti , Cristian Del Bo’
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Absorption of BBR nanoemulsions delivery systems was evaluated </span><em>in vitro</em><span> by using human colon adenocarcinoma<span> cells (Caco-2) Transwell model. The amount of permeated BBR was determined by LC-HR-MS at time zero and every 30 min for 180 min.</span></span></p></div><div><h3>Results</h3><p>Nanoemulsions significantly improved apical-to-basal transport of BBR compared to the control formulation. Kinetics of BBR uptake showed that the maximum amount absorbed was reached after 90−120 min and the percentage of BBR absorbed by Caco-2 cells increased with increasing BBR-to-Compritol ratio (1:20 > 1:10 > 1:5 > 1:1). Moreover, the formulation prepared at 80 °C showed a higher absorption rate (6-fold increment compared to control) than that developed at 25 °C (4.5-fold increment compared to control). Furthermore, demethyl-BBR was detected after 120 min of incubation as partial metabolism of berberine in the intestine.</p></div><div><h3>Conclusions</h3><p>Overall, in our <em>in vitro</em> model, these new nanoemulsions seem to potentially improve the absorption of BBR. However, <em>in vivo</em> studies are required in order to demonstrate the bioavailability of BBR from this new formulation.</p></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.phanu.2021.100279","citationCount":"4","resultStr":"{\"title\":\"An in vitro approach to study the absorption of a new oral formulation of berberine\",\"authors\":\"Mirko Marino , Claudio Gardana , Antonio Scialpi , Giuseppe Giorgini , Paolo Simonetti , Cristian Del Bo’\",\"doi\":\"10.1016/j.phanu.2021.100279\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p><span>Berberine (BBR) possesses several </span>biological activities<span> in humans, but the poor water solubility and low oral bioavailability preclude its pharmacological use. 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引用次数: 4
摘要
小檗碱(BBR)在人体中具有多种生物活性,但其水溶性差和口服生物利用度低阻碍了其药理应用。为了克服这些限制,制备了几种配方,包括包封、微乳液和纳米乳液。本研究的目的是开发一种BBR纳米乳传递系统,并利用Caco-2细胞模型评价其膜透性。方法在25℃和80℃下制备不同比例的BBR:Compritol ATO 888(脂质赋形剂)纳米乳剂。对照组由BBR和羧甲基纤维素组成。采用人结肠腺癌细胞(Caco-2) Transwell模型,对BBR纳米乳递送系统的体外吸收进行了评价。结果与对照制剂相比,纳米乳剂可显著提高BBR的根尖向基底的转运。BBR吸收动力学表明,BBR在90 ~ 120 min后达到最大吸收量,Caco-2细胞吸收BBR的百分比随着BBR与compritol比例的增加而增加(1:20;1:10祝辞1:5祝辞1:1)。此外,在80°C下制备的配方的吸收率比在25°C下制备的配方的吸收率高(比对照增加6倍)(比对照增加4.5倍)。此外,在孵育120 min后,检测到demethyl-BBR作为小檗碱在肠道的部分代谢。综上所述,在我们的体外模型中,这些新型纳米乳似乎有可能改善BBR的吸收。然而,为了证明这种新配方的BBR的生物利用度,需要进行体内研究。
An in vitro approach to study the absorption of a new oral formulation of berberine
Background
Berberine (BBR) possesses several biological activities in humans, but the poor water solubility and low oral bioavailability preclude its pharmacological use. To overcome these limitations, several formulations have been prepared including encapsulation, micro- and nano-emulsion. The aim of this study was to develop a nanoemulsion delivery system of BBR and to evaluate its membrane permeability using Caco-2 cell model.
Methods
Nanoemulsions containing different ratios BBR:Compritol ATO 888 (a lipid excipient) were formulated at 25 and 80 °C. The controls consisted of BBR and carboxymethylcellulose. Absorption of BBR nanoemulsions delivery systems was evaluated in vitro by using human colon adenocarcinoma cells (Caco-2) Transwell model. The amount of permeated BBR was determined by LC-HR-MS at time zero and every 30 min for 180 min.
Results
Nanoemulsions significantly improved apical-to-basal transport of BBR compared to the control formulation. Kinetics of BBR uptake showed that the maximum amount absorbed was reached after 90−120 min and the percentage of BBR absorbed by Caco-2 cells increased with increasing BBR-to-Compritol ratio (1:20 > 1:10 > 1:5 > 1:1). Moreover, the formulation prepared at 80 °C showed a higher absorption rate (6-fold increment compared to control) than that developed at 25 °C (4.5-fold increment compared to control). Furthermore, demethyl-BBR was detected after 120 min of incubation as partial metabolism of berberine in the intestine.
Conclusions
Overall, in our in vitro model, these new nanoemulsions seem to potentially improve the absorption of BBR. However, in vivo studies are required in order to demonstrate the bioavailability of BBR from this new formulation.