Nano-Structured Lipid Carrier-Based Oral Glutathione Formulation Mediates Renoprotection against Cyclophosphamide-Induced Nephrotoxicity, and Improves Oral Bioavailability of Glutathione Confirmed through RP-HPLC Micellar Liquid Chromatography

Abstract

The study aimed to develop a new glutathione (GSH) oral formulation to enhance the delivery of GSH and counter the nephrotoxicity of the anticancer drug, cyclophosphamide (CP). A nanostructured lipid carrier glutathione formulation (GSH-NLCs) composed of glutathione (500 mg), stearic and oleic acid (300 mg, each), and Tween® 80 (2%, w/v) was prepared through the emulsification-solvent-evaporation technique, which exhibited a 452.4 ± 33.19 nm spheroidal-sized particulate material with narrow particle size distributions, −38.5 ± 1.4 mV zeta potential, and an entrapment efficiency of 79.8 ± 1.9%. The GSH formulation was orally delivered, and biologically tested to ameliorate the CP-induced renal toxicity in a rat model. Detailed renal morphology, before and after the GSH-NLCs administration, including the histopathological examinations, confirmed the ameliorating effects of the prepared glutathione formulation together with its safe oral delivery. CP-induced oxidative stress, superoxide dismutase depletion, elevation of malondialdehyde levels, depletion of Bcl-2 concentration levels, and upregulated NF-KB levels were observed and were controlled within the recommended and near normal/control levels. Additionally, the inflammatory mediator marker, IL-1β, serum levels were marginally normalized by delivery of the GHS-NLCs formulation. Oral administration of the pure glutathione did not exhibit any ameliorating effects on the renal tissues, which suggested that the pure glutathione is reactive and is chemically transformed during the oral delivery, which affected its pharmacological action at the renal site. The protective effects of the GSH-NLCs formulation through its antioxidant and anti-inflammatory effects suggested its prominent role in containing CP-induced renal toxicity and renal tissue damage, together with the possibility of administrating higher doses of the anticancer drug, cyclophosphamide, to achieve higher and effective anticancer action in combination with the GSH-NLCs formulation.

Sesamin’s Therapeutic Actions on Cyclophosphamide-Induced Hepatotoxicity, Molecular Mechanisms, and Histopathological Characteristics

“…Liver enzymes cause cyclophosphamide to undergo metabolic modifications that result in 4-dyroxychlophosphamide. It further breaks down into two harmful metabolites, acrolein and phosphoramide mustard, which is the most toxic [24][25][26][27].…”

Ginger Extract–Loaded Transethosomes for Effective Transdermal Permeation and Anti-Inflammation in Rat Model

“… 27 GE concentration in supernatant was estimated utilizing UV–vis spectrophotometry from a calibration curve of the hydroethanolic extract of ginger (wavelength at λ max of 285 nm for maximum absorption). EE and drug loading (DL) were determined via equations (1) and (2): 28 …”

Nanostructured Lipid Carriers for Improved Delivery of Therapeutics via the Oral Route

“…In another study, the lipophilicity of two peptides, desmopressin (DES) and leuprolide (LEU), was increased by the formation of a hydrophobic ion pair (HIP) with sodium docusate as a surfactant in NLC formulations for oral delivery [197]. NLCs and lipid-based nanoparticles have been utilized in the delivery of small molecules such as RNA, and siRNA [198], replicating viral RNA (rvRNA), and s-glutathione [199], ofering them safety from enzymatic degradation and in vivo environment. Pfzer/BioNtech and Moderna developed lipid-based nanoparticle-mediated delivery of two approved COVID-19 mRNA vaccines that displayed remarkable disease control efcacy [200,201].…”