首页> 美国卫生研究院文献>Pharmaceutics >Modified Spraying Technique and Response Surface Methodology for the Preparation and Optimization of Propolis Liposomes of Enhanced Anti-Proliferative Activity against Human Melanoma Cell Line A375
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Modified Spraying Technique and Response Surface Methodology for the Preparation and Optimization of Propolis Liposomes of Enhanced Anti-Proliferative Activity against Human Melanoma Cell Line A375

机译:改进的喷雾技术和响应面方法用于蜂胶脂质体的制备和优化该胶体具有增强的抗人黑素瘤细胞系A375的抗增殖活性

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摘要

Propolis is a honeybee product that contains a mixture of natural substances with a broad spectrum of biological activities. However, the clinical application of propolis is limited due to the presence of a myriad of constituents with different physicochemical properties, low bioavailability and lack of appropriate formulations. In this study, a modified injection technique (spraying technique) has been developed for the encapsulation of the Egyptian propolis within liposomal formulation. The effects of three variables (lipid molar concentration, drug loading and cholesterol percentage) on the particle size and poly dispersity index (PDI) were studied using response surface methodology and the Box–Behnken design. Response surface diagrams were used to develop an optimized liposomal formulation of the Egyptian propolis. A comparative study between the optimized liposomal formulation prepared either by the typical ethanol injection method (TEIM) or the spraying method in terms of particle size, PDI and the in-vitro anti-proliferative effect against human melanoma cell line A375 was carried out. The spraying method resulted in the formation of smaller propolis-loaded liposomes compared to TEIM (particle sizes of 90 ± 6.2 nm, and 170 ± 14.7 nm, respectively). Furthermore, the IC50 values against A375 cells were found to be 3.04 ± 0.14, 4.5 ± 0.09, and 18.06 ± 0.75 for spray-prepared propolis liposomes (PP-Lip), TEIM PP-Lip, and propolis extract (PE), respectively. The encapsulation of PE into liposomes is expected to improve its cellular uptake by endocytosis. Moreover, smaller and more uniform liposomes obtained by spraying can be expected to achieve higher cellular uptake, as the ratio of liposomes or liposomal aggregates that fall above the capacity of cell membrane to “wrap” them will be minimized.
机译:蜂胶是一种蜜蜂产品,其中包含具有广泛生物活性的天然物质的混合物。但是,蜂胶的临床应用受到限制,原因是存在具有不同理化特性,低生物利用度和缺乏适当配方的多种成分。在这项研究中,已开发出一种改良的注射技术(喷涂技术),用于将埃及蜂胶封装在脂质体制剂中。使用响应面方法和Box–Behnken设计研究了三个变量(脂质摩尔浓度,药物载量和胆固醇百分比)对粒径和多分散指数(PDI)的影响。响应表面图用于开发埃及蜂胶的优化脂质体制剂。对通过典型乙醇注射法(TEIM)或喷雾法制备的优化脂质体制剂的粒径,PDI和对人黑素瘤细胞系A375的体外抗增殖作用进行了比较研究。与TEIM(粒径分别为90±6.2 nm和170±14.7 nm)相比,喷涂方法导致形成了更小的载有蜂胶的脂质体。此外,对于喷雾制备的蜂胶脂质体(PP-Lip),TEIM PP-Lip和蜂胶提取物(PE),发现针对A375细胞的IC50值分别为3.04±0.14、4.5±0.09和18.06±0.75。预期将PE包封入脂质体中可通过内吞作用改善其细胞摄取。此外,通过喷雾获得的更小,更均匀的脂质体有望实现更高的细胞摄取,因为脂质体或脂质体聚集体的比例要低于细胞膜“包裹”它们的能力。

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