Glutathione-Loaded Solid Lipid Microparticles as Innovative Delivery System for Oral Antioxidant Therapy
Glutathione-Loaded Solid Lipid Microparticles as Innovative Delivery System for Oral Antioxidant Therapy
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DOI：
10.3390/pharmaceutics11080364
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发表时间：
2019-08-01
期刊：
影响因子：
5.4
通讯作者：
Passerini, Nadia
中科院分区：
文献类型：
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作者：
Bertoni, Serena;Albertini, Beatrice;Passerini, Nadia
本研究旨在开发一种含有谷胱甘肽（GSH）的新型制剂，作为治疗氧化应激相关肠道疾病的口服抗氧化剂。为此目的，通过喷雾冷凝技术生产具有Dynasan 114以及Dynasan 114和Dynasan 118的混合物的固体脂质微粒（SLM）。所得SLM的主要粒径范围为250 - 355 μ m，适于口服给药。GSH以5%或20%w/w有效地装载到SLM中，并且封装过程没有改变其化学物理性质，如FT-IR、DSC和HSM分析所示。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可以有效地释放GSH在各种肠液中，而2，2-二苯基-1-苦基肼（DPPH）测定证明了该制剂良好的自由基清除活性。基于Dynasan 114的SLM在高达2000 μ g/mL的浓度下对肠HT-29细胞表现出优异的生物相容性。含有GSH单独或与另一种抗氧化剂（过氧化氢酶）一起的SLM有效降低细胞内活性氧（ROS）水平。总体而言，本研究表明，喷雾凝结的SLM是一种有前途的口服药物递送系统，用于封装一种或多种生物抗氧化剂，用于局部肠道治疗。
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 mu m, suitable for oral administration. GSH was efficiently loaded into the SLMs at 5% or 20% w/w 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 mu g/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.