Bertoni Serena, Albertini Beatrice, Facchini Carlotta, Prata Cecilia, Passerini Nadia
Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy.
Pharmaceutics. 2019 Jul 27;11(8):364. doi: 10.3390/pharmaceutics11080364.
The present study aimed to develop a novel formulation containing glutathione (GSH) as an oral antioxidant therapy for the treatment of oxidative stress-related intestinal diseases. To this purpose, solid lipid microparticles (SLMs) with Dynasan 114 and a mixture of Dynasan 114 and Dynasan 118 were produced by spray congealing technology. The obtained SLMs had main particle sizes ranging from 250 to 355 µm, suitable for oral administration. GSH was efficiently loaded into the SLMs at 5% or 20% / and the encapsulation process did not modify its chemico-physical properties, as demonstrated by FT-IR, DSC and HSM analysis. Moreover, in vitro release studies using biorelevant media showed that Dynasan 114-based SLMs could efficiently release GSH in various intestinal fluids, while 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay demonstrated the good radical scavenging activity of this formulation. Dynasan 114-based SLMs exhibited an excellent biocompatibility on intestinal HT-29 cells at concentrations up to 2000 μg/mL. SLMs containing GSH alone or together with another antioxidant agent (catalase) were effective in reducing intracellular reactive oxygen species (ROS) levels. Overall, this study indicated that spray congealed SLMs are a promising oral drug delivery system for the encapsulation of one or more biological antioxidant agents for local intestinal treatment.
本研究旨在开发一种含有谷胱甘肽（GSH）的新型制剂，作为口服抗氧化疗法用于治疗与氧化应激相关的肠道疾病。为此，采用喷雾冷凝技术制备了含有Dynasan 114以及Dynasan 114和Dynasan 118混合物的固体脂质微粒（SLMs）。所获得的SLMs主要粒径范围为250至355μm，适合口服给药。GSH以5%或20%的比例有效负载到SLMs中，并且如傅里叶变换红外光谱（FT-IR）、差示扫描量热法（DSC）和高光谱显微镜（HSM）分析所示，包封过程未改变其化学物理性质。此外，使用生物相关介质的体外释放研究表明，基于Dynasan 114的SLMs能够在各种肠液中有效释放GSH，而2,2-二苯基-1-苦基肼（DPPH）测定表明该制剂具有良好的自由基清除活性。基于Dynasan 114的SLMs在浓度高达2000μg/mL时对肠道HT-29细胞表现出优异的生物相容性。单独含有GSH或与另一种抗氧化剂（过氧化氢酶）一起的SLMs在降低细胞内活性氧（ROS）水平方面是有效的。总体而言，本研究表明喷雾冷凝的SLMs是一种有前景的口服药物递送系统，可用于包封一种或多种生物抗氧化剂以进行局部肠道治疗。
