Department of Drug Delivery Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
Osaka R&D Center, Mitsubishi Chemical Corporation, Ibaraki, Osaka, Japan.
AAPS PharmSciTech. 2020 May 20;21(5):150. doi: 10.1208/s12249-020-01670-8.
Emulsions for oral delivery are not suitable for sustained drug absorption because such preparations diffuse rapidly in the gastrointestinal (GI) tract after oral administration. In order to generate sustained drug absorption and increase oral bioavailability, various polymers were added to a morin (MO) nanoemulsion to improve retention in the GI tract and alter the surface properties of oil droplets in the nanoemulsion. The influence of these polymers on the formulation properties was investigated. The area under the blood concentration-time curve (AUC) and the mean residence time (MRT) after oral administration of the nanoemulsions were measured, and the influence of the polymers on bioavailability was investigated. Chitosan (Chi) addition MO nanoemulsion (MO-Chi nanoemulsion) showed the highest AUC and MRT. MO-Chi nanoemulsion increased retention in the GI tract because of the relatively higher viscosity and high affinity between mucin and Chi covering the oil droplets. Furthermore, MO-Chi nanoemulsion could maintain the drug in oil droplets by suppression of drug release through the polymer hydration layer, and sustained drug release achieved continuous drug absorption. Nanoemulsions with sodium carboxymethylcellulose and poly-γ-glutamic acid potassium salt showed the next highest AUC and MRT after MO-Chi nanoemulsion. From these results, it was suggested that by increasing the viscosity of the nanoemulsion, there was high affinity between the added polymer and mucin, and sustained drug release was useful for enhancing the bioavailability of the polymer-containing nanoemulsions.
用于口服的乳剂并不适合用于持续药物吸收，因为这些制剂在口服后会在胃肠道（GI）中迅速扩散。为了产生持续的药物吸收并提高口服生物利用度，各种聚合物被添加到芦丁（MO）纳米乳中，以改善在胃肠道中的保留并改变纳米乳中油滴的表面性质。研究了这些聚合物对制剂性质的影响。测量了纳米乳口服后的血药浓度-时间曲线下面积（AUC）和平均驻留时间（MRT），并研究了聚合物对生物利用度的影响。壳聚糖（Chi）添加 MO 纳米乳（MO-Chi 纳米乳）表现出最高的 AUC 和 MRT。MO-Chi 纳米乳增加了在胃肠道中的保留，因为相对较高的粘度和覆盖油滴的粘蛋白和 Chi 之间的高亲和力。此外，MO-Chi 纳米乳可以通过聚合物水合层抑制药物释放来维持油滴中的药物，从而实现持续的药物释放和持续的药物吸收。与 MO-Chi 纳米乳相比，羧甲基纤维素钠和聚谷氨酸钾盐的纳米乳表现出下一个最高的 AUC 和 MRT。从这些结果可以看出，通过增加纳米乳的粘度，可以增加添加聚合物与粘蛋白之间的亲和力，并且持续的药物释放有助于提高含聚合物纳米乳的生物利用度。
