Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 26470 Eskişehir, Turkey.
Anadolu University, Graduate School of Health Sciences, Department of Pharmaceutical Technology, 26470 Eskişehir, Turkey.
Microvasc Res. 2020 Jul;130:103991. doi: 10.1016/j.mvr.2020.103991. Epub 2020 Feb 24.
The development of a new drug active substance is not only time-consuming and expensive, but also a chain of operations that often fails. However, increasing the bioavailability, effectiveness, safety, or targeting the drugs used in clinic by various methods, such as nanoparticles (NPs), may be a more effective way of using them in clinic. In addition, NP formulations are becoming increasingly popular in modern medical treatments. Angiogenesis, formation of new capillaries from a pre-existing one, fundamentally occurs in physiological processes such as wound healing, embryogenesis and menstrual cycle, also has a vital role in pathology of cancer, psoriasis, diabetic retinopathy and chronic inflammation. The Hen's Egg Test on the Chorioallantoic Membrane (HET-CAM) assay is a useful, well established and animal alternative in vivo procedure for evaluation of anti-inflammatory potentials and anti-irritant properties of nano drug delivery systems. In this study, diclofenac sodium (DS) loaded PLGA NPs were prepared and characterized. The particle size (PS) of DS-loaded PLGA NPs was between 114.7 and 124.8 nm and all NPs were monodisperse with negative zeta potential values. The encapsulation efficiency was in range of 41.4-77.8%. In vitro dissolution studies of NPs showed up to 24 h of DS release after the first 3 h of burst effect. The 3 h burst effect and 24 h release kinetics studied with DDSolver were found to be predominantly driven not only by one mechanism, by a combined mechanism of Fickian and non-Fickian. Solid state structures of formulations were clarified by DSC and FT-IR analysis. PS, EE% and release rates were found to be affected by the amount of DS added to the formulations. Increasing the amount of DS added to the formulations increased PS, while the EE% decreased. The release rates were affected by PS and the formulation with the lowest PS value showed slower release. The anti-inflammatory activity of optimum formulation (NP-1) was examined using in vivo HET-CAM assay. The anti-inflammatory activity results indicated that NP-1 coded NP formulation showed significantly good anti-inflammatory potential at low dose. As a result, a low dose high anti-inflammatory effect was achieved with the NP structure of DS. To the best of our knowledge this is the first study on in vivo anti-inflammatory activities of DS loaded PLGA NPs by HET-CAM.
新药物活性物质的开发不仅耗时且昂贵，而且经常会出现一系列失败的操作。然而，通过各种方法（如纳米颗粒（NPs））提高临床使用的药物的生物利用度、有效性、安全性或靶向性，可能是在临床上更有效地使用它们的一种方法。此外，NP 制剂在现代医疗治疗中越来越受欢迎。血管生成，即从预先存在的毛细血管中形成新的毛细血管，从根本上发生在伤口愈合、胚胎发生和月经周期等生理过程中，在癌症、银屑病、糖尿病性视网膜病变和慢性炎症等病理学中也起着至关重要的作用。鸡胚绒毛尿囊膜（HET-CAM）试验是一种有用的、成熟的动物体内替代方法，可用于评估纳米药物递送系统的抗炎潜力和抗刺激性。在这项研究中，制备并表征了载有双氯芬酸钠（DS）的 PLGA NPs。载有 DS 的 PLGA NPs 的粒径（PS）在 114.7 至 124.8nm 之间，所有 NPs 均为单分散且具有负的zeta 电位值。包封效率在 41.4-77.8%之间。NPs 的体外溶解研究表明，在 3 小时的突释效应后，DS 释放可达 24 小时。用 DDSolver 研究的 3 小时突释效应和 24 小时释放动力学发现，不仅由一种机制驱动，而且由菲克和非菲克的联合机制驱动。通过 DSC 和 FT-IR 分析澄清了制剂的固态结构。PS、EE%和释放速率受到添加到制剂中的 DS 量的影响。向制剂中添加的 DS 量增加，PS 增加，而 EE%降低。释放速率受 PS 影响，PS 值最低的制剂释放较慢。使用体内 HET-CAM 试验研究了最佳制剂（NP-1）的抗炎活性。抗炎活性结果表明，编码 NP 制剂的 NP-1 在低剂量下表现出明显良好的抗炎潜力。因此，DS 的 NP 结构实现了低剂量高抗炎效果。据我们所知，这是首次通过 HET-CAM 研究载有 DS 的 PLGA NPs 的体内抗炎活性。
