Glutathione-Loaded Solid Lipid Microparticles as Innovative Delivery System for Oral Antioxidant Therapy

Abstract

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% 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 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.

Stable solid dispersion of lurasidone hydrochloride with augmented physicochemical properties for the treatment of schizophrenia and bipolar disorder

“…The DSC characterization results showed characteristic endothermic peak at 147.08°C for LH plain drug which is considered as its melting point representing crystalline nature and was matching with reported values (Qian et al, 2017). GSH showed its sharp melting endothermic peak at the temperature of 199.38°C which is also comparable with the literature value (Bertoni, Albertini, Facchini, Prata, & Passerini, 2019). The observed two sharp endothermic peaks at 147.19 and 201.22°C for LH‐GSH PM represents melting of LH and GSH respectively, individually at their respective melting points.…”

“…The PXRD patterns of LH plain drug showed characteristic diffraction peaks at 2θ values which were lying in association with the reported values pertaining to crystalline nature (Qian et al, 2017). Similarly, GSH showed its characteristic 2θ value which also resembles to the literature values (Bertoni et al, 2019). The characteristic diffraction peaks of LH and GSH were retained in LH‐GSH PM.…”

“…The DSC characterization results showed characteristic endothermic peak at 147.08°C for LH plain drug which is considered as its melting point representing crystalline nature and was matching with reported values (Qian et al, 2017). GSH showed its sharp melting endothermic peak at the temperature of 199.38°C which is also comparable with the literature value (Bertoni, Albertini, Facchini, Prata, & Passerini, 2019 endotherm with disappearance of melting endotherm of LH and this might be attributed to complete dispersion of LH within the matrix of GSH (Lopedota et al, 2009). Joe et al, have also reported three SDs of poorly water-soluble tacrolimus with hydroxypropyl-beta-cyclodextrin and dioctyl sulfosuccinate using a spray-drying technique via the solvent-evaporation method (Joe et al, 2010).…”

Liquid Lipids Act as Polymorphic Modifiers of Tristearin-Based Formulations Produced by Melting Technologies

“…Among lipid-based oral drug delivery systems, lipid microparticles (MPs) are versatile drug delivery systems that offer flexibility in both drug release and final dosage form. The wide variety of available matrices and formulation approaches make MPs amenable to a broad range of targeted release kinetics and delivery strategies (taste masking, delayed or controlled release) [ 47 , 48 , 49 , 50 ]. MPs can be administered as sachets or incorporated into capsules and tablets or even suspended to obtain a liquid formulation.…”

Lipid composition optimization in spray congealing technique and testing with curcumin-loaded microparticles

“…In fact, works involving solid lipid matrices, including the ones produced by spray congealing [4] or alternative methods [34,35], were mainly focused on the encapsulation of pharmaceuticals or drugs for delivery applications [36], but not on natural bioactives and/or colorants, namely curcumin. Moreover, the optimization of the system through the use of experimental design strategies, provides a predictive tool to validate new lipid formulations, positioning the present work as an innovative strategy in comparison to other works where formulations [37,38] or spray congealing process parameters [4] are tested by conventional trial/error methods.…”