Assali Mohyeddin, Zohud Nihal
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine.
Drug Dev Res. 2021 May;82(3):448-457. doi: 10.1002/ddr.21768. Epub 2020 Dec 1.
Indomethacin is one of the nonsteroidal anti-inflammatory drugs (NSAIDs) that are widely prescribed drug for pain and inflammation. However, its notoriety of causing gastrointestinal effect, low water solubility, and its short half-life would affect patient compliance and its oral absorption and accordingly justify the need to develop a formula with a controlled and sustained release manner in combination with anti-ulcer drugs. Herein, we synthesized indomethacin-paracetamol co-drug loaded in nanoemulsion and encapsulated in famotiditine loaded polycaprolactone (PCL) nanoparticles. The synthesis of the co-drug was achieved by the formation of a hydrolyzable ester between the indomethacin and paracetamol. The synthesized co-drug was preloading in nanoemulsion (Co-NE), which encapsulated into famotidine PCL nanoparticles utilizing the nanoprecipitation approach. The developed nanosystem showed hydrodynamic size less than 200 nm and the zeta potential value above -30 mV. TEM images confirmed the morphological structure of the formed nanoemulsion and the loaded PCL nanoparticles. Stability studies revealed that the developed nanosystem was stable at different temperatures and pHs over 1 month. Moreover, improvement of the solubilities of these three drugs leading to have a controlled-release multicomponent system of both co-drug and famotidine over 3 days. This multicomponent nanoparticle might be a potential platform to overcome the obstacles of NSAIDs, synergize drugs with different mechanisms of actions by co-encapsulating a small-sized nanoemulsion into PCL nanoparticles for reaching the goal of effective anti-inflammatory therapy.
吲哚美辛是一种非甾体抗炎药（NSAIDs），是广泛用于止痛和抗炎的处方药。然而，其引起胃肠道不良反应的恶名、低水溶性以及短半衰期会影响患者的依从性及其口服吸收，因此有必要开发一种与抗溃疡药物联合的控释和缓释剂型。在此，我们合成了负载于纳米乳剂并包裹于法莫替丁负载的聚己内酯（PCL）纳米颗粒中的吲哚美辛-对乙酰氨基酚共药。共药的合成是通过吲哚美辛和对乙酰氨基酚之间形成可水解酯来实现的。合成的共药预先负载于纳米乳剂（Co-NE）中，然后利用纳米沉淀法将其包裹于法莫替丁PCL纳米颗粒中。所开发的纳米系统的流体动力学尺寸小于200nm，zeta电位值高于-30mV。透射电镜图像证实了所形成的纳米乳剂和负载的PCL纳米颗粒的形态结构。稳定性研究表明，所开发的纳米系统在不同温度和pH值下1个月内均稳定。此外，这三种药物的溶解度得到改善，从而形成了共药和法莫替丁的控释多组分系统，持续3天。这种多组分纳米颗粒可能是一个潜在的平台，可克服NSAIDs的障碍，通过将小型纳米乳剂共包裹于PCL纳米颗粒中，使具有不同作用机制的药物协同作用，以实现有效的抗炎治疗目标。
