Comparison of migration disturbance potency of epigallocatechin gallate (EGCG) synthetic analogs and EGCG PEGylated PLGA nanoparticles in rat neurospheres

Abstract

Epigallocatechin gallate (EGCG), the main catechin of green tea, is described to have potential health benefits in several fields like oncology, neurology or cardiology. Currently, it is also under pre-clinical investigation as a potential therapeutic or preventive treatment during pregnancy against developmental adverse effects induced by toxic substances. However, the safety of EGCG during pregnancy is unclear due to its proven adverse effects on neural progenitor cells' (NPCs) migration. As lately several strategies have arisen to generate new therapeutic agents derived from EGCG, we have used the rat 'Neurosphere Assay' to characterize and compare the effects of EGCG structurally related compounds and EGCG PEGylated PLGA nanoparticles on a neurodevelopmental key event: NPCs migration. Compounds structurally-related to EGCG induce the same pattern of NPCs migration alterations (decreased migration distance, decreased formation of migration corona, chaotic orientation of cellular processes and decreased migration of neurons at higher concentrations). The potency of the compounds does not depend on the number of galloyl groups, and small structure variations can imply large potency differences. Due to their lower toxicity observed in vitro in NPCs, 4,4,5trihydroxybenzoyl)oxy]-1,1'-biphenyl and EGCG PEGylated PLGA nanoparticles are suggested as potential future therapeutic or preventive alternatives to EGCG during prenatal period.

Scientific Validation of Human Neurosphere Assays for Developmental Neurotoxicity Evaluation

“…Moreover, we assessed the effects of a large variety of compounds on the Neurosphere Assay KEs and studied their MoA for some of them ( Fritsche et al, 2005 ; Moors et al, 2007 ; Schreiber et al, 2010 ; Gassmann et al, 2010 , 2014 ; Baumann et al, 2016 ; Barenys et al, 2017 ; Masjosthusmann et al, 2019 , 2020 ; Klose et al, 2021b , 2021a ). In addition, species aspects were investigated using time-matched ( Clancy et al, 2007 ) rat, mouse or rabbit neurospheres ( Gassmann et al, 2010 ; Baumann et al, 2016 ; Barenys et al, 2017 , 2021 ; Dach et al, 2017 ; Masjosthusmann et al, 2018 , 2019 ; Ali et al, 2019 ; Kühne et al, 2019 ; Klose et al, 2021b ). On the regulatory side, data from the Neurosphere Assay was used for hazard characterization of deltamethrin and flufenacet building an IATA ( Hernández-Jerez et al, 2021 ).…”

Polymeric Guide Conduits for Peripheral Nerve Tissue Engineering

“…PLGA (PAA: PLLA 50:50) scaffolds have been widely used for fabricating NGCs, and these NGCs have been demonstrated to promote axonal regeneration (Lackington et al, 2019). The degradation byproducts of PLGA are lactic and glycolic acid that have high acidity, and metabolization is difficult in vivo (Kühne et al, 2018). However, PLGA, as a widely studied material, has been used in many commercial conduits without causing metabolic problems due to the degradation byproducts.…”

Recent Advances in Nanoencapsulation of Phytochemicals to Combat Obesity and Its Comorbidities

“…trans -Resveratrol, EGCG, and curcumin have been encapsulated into PLGA nanoparticles for improving their characteristics and bioactivities. PLGA is a FDA-approved material for making medical devices .…”

“…38 The common preparation methods for polymeric nanoparticles include emulsification−diffusion, nanoprecipitation, and solvent evaporation methods. 2 trans-Resveratrol, 39 EGCG, 40 and curcumin 41 have been encapsulated into PLGA nanoparticles for improving their characteristics and bioactivities. PLGA is a FDA-approved material for making medical devices.…”