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基于微流控技术制备的载精油壳聚糖包衣聚乳酸-羟基乙酸共聚物颗粒可提高其生物利用度和杀线虫活性。

Microfluidic-Based Formulation of Essential Oils-Loaded Chitosan Coated PLGA Particles Enhances Their Bioavailability and Nematocidal Activity.

作者信息

Helal Mohamed A, Abdel-Gawad Ahmed M, Kandil Omnia M, Khalifa Marwa M E, Morrison Alison A, Bartley David J, Cave Gareth W V, Elsheikha Hany M

机构信息

School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK.

Department of Parasitology and Animal Diseases, Veterinary Research Institute, National Research Centre, Giza 12622, Egypt.

出版信息

Pharmaceutics. 2022 Sep 23;14(10):2030. doi: 10.3390/pharmaceutics14102030.

DOI:10.3390/pharmaceutics14102030
PMID:36297465
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9608619/
Abstract

In this study, poly (lactic-co-glycolic) acid (PLGA) particles were synthesized and coated with chitosan. Three essential oil (EO) components (eugenol, linalool, and geraniol) were entrapped inside these PLGA particles by using the continuous flow-focusing microfluidic method and a partially water-miscible solvent mixture (dichloromethane: acetone mixture (1:10)). Encapsulation of EO components in PLGA particles was confirmed by Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction, with encapsulation efficiencies 95.14%, 79.68%, and 71.34% and loading capacities 8.88%, 8.38%, and 5.65% in particles entrapped with eugenol, linalool, and geraniol, respectively. The EO components’ dissociation from the loaded particles exhibited an initial burst release in the first 8 h followed by a sustained release phase at significantly slower rates from the coated particles, extending beyond 5 days. The EO components encapsulated in chitosan coated particles up to 5 μg/mL were not cytotoxic to bovine gut cell line (FFKD-1-R) and had no adverse effect on cell growth and membrane integrity compared with free EO components or uncoated particles. Chitosan coated PLGA particles loaded with combined EO components (10 µg/mL) significantly inhibited the motility of the larval stage of Haemonchus contortus and Trichostrongylus axei by 76.9%, and completely inhibited the motility of adult worms (p < 0.05). This nematocidal effect was accompanied by considerable cuticular damage in the treated worms, reflecting a synergistic effect of the combined EO components and an additive effect of chitosan. These results show that encapsulation of EO components, with a potent anthelmintic activity, in chitosan coated PLGA particles improve the bioavailability and efficacy of EO components against ovine gastrointestinal nematodes.

摘要

在本研究中，合成了聚（乳酸-乙醇酸）共聚物（PLGA）颗粒并用壳聚糖进行包衣。通过连续流动聚焦微流控方法和部分与水混溶的溶剂混合物（二氯甲烷：丙酮混合物（1:10））将三种精油（EO）成分（丁香酚、芳樟醇和香叶醇）包裹在这些PLGA颗粒内。通过傅里叶变换红外光谱、热重分析和X射线衍射确认了EO成分在PLGA颗粒中的包封情况，包封率分别为95.14%、79.68%和71.34%，载药量分别为8.88%、8.38%和5.65%，载有丁香酚、芳樟醇和香叶醇的颗粒中载药量依次降低。EO成分从负载颗粒中的解离在最初8小时表现为突发释放，随后从包衣颗粒以显著较慢的速率进入持续释放阶段，持续时间超过5天。包封在壳聚糖包衣颗粒中浓度高达5μg/mL的EO成分对牛肠道细胞系（FFKD-1-R）无细胞毒性，与游离EO成分或未包衣颗粒相比，对细胞生长和膜完整性没有不良影响。负载联合EO成分（10μg/mL）的壳聚糖包衣PLGA颗粒显著抑制捻转血矛线虫和奥氏奥斯特线虫幼虫阶段的运动性达76.9%，并完全抑制成虫的运动性（p<0.05）。这种杀线虫作用伴随着处理后虫体明显的表皮损伤，反映了联合EO成分的协同作用和壳聚糖的加和作用。这些结果表明，将具有强效驱虫活性的EO成分包封在壳聚糖包衣的PLGA颗粒中可提高EO成分对绵羊胃肠道线虫的生物利用度和功效。

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