{"title":"促进大麻二酚肠道吸收的新型纳米乳剂的研制。","authors":"Yukako Nakano, Masataka Tajima, Erika Sugiyama, Vilasinee Hirunpanich Sato, Hitoshi Sato","doi":"10.1159/000497361","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Cannabidiol (CBD) is highly lipophilic, and its oral bioavailability is known to be very low in humans. In this study, we developed a novel nanoemulsion preparation of CBD (CBD-NE) to improve the poor solubility and absorption of CBD. The pharmacokinetic profiles of CBD in rats were evaluated after oral administrations of CBD oil and CBD-NE, and the effect of bile secretion on CBD absorption was also evaluated.</p><p><strong>Methods: </strong>The CBD-NE formulation developed in this study consisted of vitamin E acetate, ethanol, Tween-20, and distilled water (1.7/3.8/70/24.5, w/w%). A CBD oil formulation (CBD oil, control) 100 mg/kg or CBD-NE 50 mg/kg was orally administered to rats, and the blood samples were collected over time. Moreover, the CBD oil or CBD-NE was orally administered to bile-fistulated rats, and the pharmacokinetic profiles of CBD were also evaluated. CBD concentrations in plasma were measured using LC-MS/MS.</p><p><strong>Results: </strong>The particle size of CBD-NE was 35.3 ± 11.8 nm. Mean T<sub>max</sub> of CBD-NE was shortened significantly by the factor of 3 (from 8.00 to 2.40 h, <i>p</i> < 0.001) and AUC<sub>0-</sub><sub>∞</sub>/dose increased by 65% (from 0.272 ± 0.045 to 0.448 ± 0.087 h L/kg) compared with CBD oil. AUC<sub>0-</sub><sub>∞</sub>/dose and C<sub>max</sub>/dose after oral administration of CBD oil were significantly reduced by the factor of 27 and 23 (<i>p</i> < 0.05 and <i>p</i> < 0.01), respectively, in bile-fistulated rats compared with the untreated rats. In contrast, all pharmacokinetic parameters after oral administration of CBD-NE were not significantly different between the untreated and bile-fistulated rats. Therefore, these results demonstrated that conventional CBD oil formulation but not CBD-NE requires bile-mediated micelle formation.</p><p><strong>Conclusions: </strong>The novel NE formulation developed in this study successfully improved the absorption of CBD regardless of bile secretion. The newly developed oral CBD-NE preparation could be useful to achieve a more stable and quicker onset of action by CBD.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"2 1","pages":"35-42"},"PeriodicalIF":0.0000,"publicationDate":"2019-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000497361","citationCount":"50","resultStr":"{\"title\":\"Development of a Novel Nano-emulsion Formulation to Improve Intestinal Absorption of Cannabidiol.\",\"authors\":\"Yukako Nakano, Masataka Tajima, Erika Sugiyama, Vilasinee Hirunpanich Sato, Hitoshi Sato\",\"doi\":\"10.1159/000497361\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Cannabidiol (CBD) is highly lipophilic, and its oral bioavailability is known to be very low in humans. In this study, we developed a novel nanoemulsion preparation of CBD (CBD-NE) to improve the poor solubility and absorption of CBD. The pharmacokinetic profiles of CBD in rats were evaluated after oral administrations of CBD oil and CBD-NE, and the effect of bile secretion on CBD absorption was also evaluated.</p><p><strong>Methods: </strong>The CBD-NE formulation developed in this study consisted of vitamin E acetate, ethanol, Tween-20, and distilled water (1.7/3.8/70/24.5, w/w%). A CBD oil formulation (CBD oil, control) 100 mg/kg or CBD-NE 50 mg/kg was orally administered to rats, and the blood samples were collected over time. Moreover, the CBD oil or CBD-NE was orally administered to bile-fistulated rats, and the pharmacokinetic profiles of CBD were also evaluated. CBD concentrations in plasma were measured using LC-MS/MS.</p><p><strong>Results: </strong>The particle size of CBD-NE was 35.3 ± 11.8 nm. Mean T<sub>max</sub> of CBD-NE was shortened significantly by the factor of 3 (from 8.00 to 2.40 h, <i>p</i> < 0.001) and AUC<sub>0-</sub><sub>∞</sub>/dose increased by 65% (from 0.272 ± 0.045 to 0.448 ± 0.087 h L/kg) compared with CBD oil. AUC<sub>0-</sub><sub>∞</sub>/dose and C<sub>max</sub>/dose after oral administration of CBD oil were significantly reduced by the factor of 27 and 23 (<i>p</i> < 0.05 and <i>p</i> < 0.01), respectively, in bile-fistulated rats compared with the untreated rats. In contrast, all pharmacokinetic parameters after oral administration of CBD-NE were not significantly different between the untreated and bile-fistulated rats. Therefore, these results demonstrated that conventional CBD oil formulation but not CBD-NE requires bile-mediated micelle formation.</p><p><strong>Conclusions: </strong>The novel NE formulation developed in this study successfully improved the absorption of CBD regardless of bile secretion. 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引用次数: 50
摘要
背景:大麻二酚(CBD)具有高度亲脂性，已知其在人体中的口服生物利用度非常低。在这项研究中，我们开发了一种新的CBD纳米乳液制剂(CBD- ne)，以改善CBD的溶解性和吸收性。研究了口服CBD油和CBD- ne后大鼠体内CBD的药代动力学特征，并评估了胆汁分泌对CBD吸收的影响。方法:以维生素E醋酸酯、乙醇、Tween-20、蒸馏水(1.7/3.8/70/24.5,w/w%)为主要原料制备CBD-NE。给大鼠口服CBD油制剂(CBD油，对照)100 mg/kg或CBD- ne 50 mg/kg，并随时间采集血样。此外，将CBD油或CBD- ne口服给胆瘘大鼠，并评估CBD的药代动力学特征。采用LC-MS/MS法测定血浆中CBD浓度。结果:CBD-NE的粒径为35.3±11.8 nm。与CBD油相比，CBD- ne的平均Tmax缩短了3倍(从8.00到2.40 h, p < 0.001)， AUC0-∞/剂量增加了65%(从0.272±0.045到0.448±0.087 h L/kg)。与未给药大鼠相比，口服CBD油后胆瘘大鼠AUC0-∞/剂量和Cmax/剂量分别显著降低27和23倍(p < 0.05和p < 0.01)。相比之下，口服CBD-NE后的所有药代动力学参数在未治疗的大鼠和胆瘘大鼠之间没有显著差异。因此，这些结果表明，传统的CBD油配方而不是CBD- ne需要胆汁介导的胶束形成。结论:本研究开发的新型NE配方成功地改善了CBD的吸收，而不影响胆汁分泌。新开发的口服CBD- ne制剂可用于实现CBD更稳定和更快的起效。
Development of a Novel Nano-emulsion Formulation to Improve Intestinal Absorption of Cannabidiol.
Background: Cannabidiol (CBD) is highly lipophilic, and its oral bioavailability is known to be very low in humans. In this study, we developed a novel nanoemulsion preparation of CBD (CBD-NE) to improve the poor solubility and absorption of CBD. The pharmacokinetic profiles of CBD in rats were evaluated after oral administrations of CBD oil and CBD-NE, and the effect of bile secretion on CBD absorption was also evaluated.
Methods: The CBD-NE formulation developed in this study consisted of vitamin E acetate, ethanol, Tween-20, and distilled water (1.7/3.8/70/24.5, w/w%). A CBD oil formulation (CBD oil, control) 100 mg/kg or CBD-NE 50 mg/kg was orally administered to rats, and the blood samples were collected over time. Moreover, the CBD oil or CBD-NE was orally administered to bile-fistulated rats, and the pharmacokinetic profiles of CBD were also evaluated. CBD concentrations in plasma were measured using LC-MS/MS.
Results: The particle size of CBD-NE was 35.3 ± 11.8 nm. Mean Tmax of CBD-NE was shortened significantly by the factor of 3 (from 8.00 to 2.40 h, p < 0.001) and AUC0-∞/dose increased by 65% (from 0.272 ± 0.045 to 0.448 ± 0.087 h L/kg) compared with CBD oil. AUC0-∞/dose and Cmax/dose after oral administration of CBD oil were significantly reduced by the factor of 27 and 23 (p < 0.05 and p < 0.01), respectively, in bile-fistulated rats compared with the untreated rats. In contrast, all pharmacokinetic parameters after oral administration of CBD-NE were not significantly different between the untreated and bile-fistulated rats. Therefore, these results demonstrated that conventional CBD oil formulation but not CBD-NE requires bile-mediated micelle formation.
Conclusions: The novel NE formulation developed in this study successfully improved the absorption of CBD regardless of bile secretion. The newly developed oral CBD-NE preparation could be useful to achieve a more stable and quicker onset of action by CBD.
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