PLGA Microspheres Loaded with β-Cyclodextrin Complexes of Epigallocatechin-3-Gallate for the Anti-Inflammatory Properties in Activated Microglial Cells

Abstract

Although epigallocatechin-3-gallate (EG) is well-known as a potent antioxidant and free radical scavenger for neurodegenerative diseases, it still has disadvantages that reduce its treatment effectiveness due to low bioavailability, slow absorption, and water solubility. Therefore, the aim of this study is to improve the bioavailability of EG and increase the effectiveness of anti-inflammatory properties to microglial cells by using Poly(Lactide-co-Glycolide) (PLGA) microspheres as carriers. In this study, we used UV–Vis spectroscopy to show the formation of the complex of β-cyclodextrin (β-CD) and EG (CD-EG). The loading efficiency of EG in PLGA microspheres was optimized by the addition of β-CD. The highest loading efficiency of 16.34% was found among other formulations. The results of Fourier transform infrared spectroscopy indicated the loading of CD-EG in PLGA microspheres. The scanning electron microscopic images demonstrated the spherical PLGA particles with controlled particles size ranging from 1–14 µm. Moreover, the in vitro release of EG was conducted to explore the sustained release property of the PLGA formulations. In the in vitro model of mouse microglial cells (BV-2 cells) stimulated by lipopolysaccharide, the cytotoxicity test showed that for up to 1 mg/mL of PLGA microspheres no toxicity to BV-2 cells was found. PLGA microspheres can significantly suppress the nitric oxide production from BV-2 cells, indicating EG loaded in PLGA microspheres can suppress the inflammation of activated microglial cells. Furthermore, the intracellular iNOS in BV-2 cells was also found to be down regulated. In summary, we have successfully shown that the use of β-CD can increase the loading efficiency of EG in PLGA microspheres and provide neuroprotective effect on the activated microglial cells.

Epigallocatechin-3-Gallate-Loaded Liposomes Favor Anti-Inflammation of Microglia Cells and Promote Neuroprotection

“…It was increasing with a higher concentration of EGCG or longer reaction time. The particle size of PC-EGCG-VE- and PS-EGCG-VE-liposomes were 161.5 and 142.9 nm, which were smaller than that of EGCG loaded in PLGA microspheres [ 28 ] with additional β-cyclodextrin (ranging from 1–14 µm). The encapsulation efficiency of PC-EGCG-VE- and PS-EGCG-VE-liposomes were 60.2% and 76.8%, respectively.…”

“…In the present study, EGCG pretreatment can reduce the release of NO. Suppression of NO production from LPS-induced BV-2 cells by pretreatment of EGCG-loaded PLGA microspheres was also investigated in our previous study [ 28 ].…”

“…In addition, post-treatment of EGCG on LPS-injured mice decreased production of a pro-inflammatory cytokine through modulating the TLR4-NF-κB pathway [ 27 ]. Moreover, poly(lactide-co-glycolide) (PLGA) microspheres loaded with EGCG and optimized by the addition of β-cyclodextrin (β-CD) could effectively suppress NO production from BV-2 cells in the in vitro model of murine BV-2 microglial cells stimulated by LPS, indicating the microspheres can suppress inflammation of activated microglial cells [ 28 ].…”

Nanoformulations to Enhance the Bioavailability and Physiological Functions of Polyphenols

“…The use of PLA/PLGA nanoparticles improves the water solubility and poor stability of polyphenols. The release kinetics of polyphenol-PLA/PLGA nanoparticles in vitro show rapid release are at first followed by slow release, which demonstrates the controlled release of polyphenol compounds from PLA/PLGA nanoparticles [ 214 ]. Similar to other nanoparticles, PLA/PLGA also enhances the functional activity of polyphenols, such as anti-inflammatory, antioxidant and anti-cancer properties [ 215 , 216 , 217 ].…”

Surface‐enhanced Raman spectroscopy for successful probing of itraconazole within poly(lactic‐co‐glycolic acid) nanoparticles

“…Different biocompatible polymeric‐based platforms were developed in recent years for drug delivery of hydrophobic drugs while addressing the target of specific organs and tissues, as, for instance, the poly(lactic‐ co ‐glycolic acid) (PLGA), which is one of the most successful biodegradable polymeric‐based platforms . The inherent biodegradability observed in PLGA is related to its in vivo hydrolysis capability, producing nontoxic metabolites while allowing high tolerable doses.…”