Electrospray-Based Microencapsulation of Epigallocatechin 3-Gallate for Local Delivery into the Intervertebral Disc

Abstract

Locally delivered anti-inflammatory compounds can restore the homeostasis of the degenerated intervertebral disc (IVD). With beneficial effects on IVD cells, epigallocatechin 3-gallate (EGCG) is a promising therapeutic candidate. However, EGCG is prone to rapid degradation and/or depletion. Therefore, the purpose of this study was to develop a method for controlled EGCG delivery in the degenerated IVD. Primary IVD cells were isolated from human donors undergoing IVD surgeries. EGCG was encapsulated into microparticles by electrospraying of glutaraldehyde-crosslinked gelatin. The resulting particles were characterized in terms of cytocompatibility and anti-inflammatory activity, and combined with a thermoresponsive carrier to produce an injectable EGCG delivery system. Subsequently, electrospraying was scaled up using the industrial NANOSPIDER™ technology. The produced EGCG microparticles reduced the expression of inflammatory (IL-6, IL-8, COX-2) and catabolic (MMP1, MMP3, MMP13) mediators in pro-inflammatory 3D cell cultures. Combining the EGCG microparticles with the carrier showed a trend towards modulating EGCG activity/release. Electrospray upscaling was achieved, leading to particles with homogenous spherical morphologies. In conclusion, electrospray-based encapsulation of EGCG resulted in cytocompatible microparticles that preserved the activity of EGCG and showed the potential to control EGCG release, thus favoring IVD health by downregulating local inflammation. Future studies will focus on further exploring the biological activity of the developed delivery system for potential clinical use.

In vitro antioxidant and antidiabetic activity of essential oils encapsulated in gelatin‐pectin particles against sugar, lipid and protein oxidation and amylase and glucosidase activity

“…Gelatin‐pectin‐essential oil nanoparticles have a spherical shape and are well dispersed. The globular shape of nanoparticles makes them the most capable of controlled release and protects the payloads because the spherical shape has the longest path to the movement of the entrapped extract in the nanoparticles and also the lowest contact area with the dispersed phase aqueous medium compared to other forms of nanoparticles (Loepfe et al., 2019). The extracted plants essential oils did not have a significant impact on the topology of the particles but improved their biological activity.…”

New Hope for Treating Intervertebral Disc Degeneration: Microsphere-Based Delivery System

“…However, the stability of EGCG is susceptible to its environment (enzymes, temperature, pH), and therefore it is difficult to maintain high biological activity ( Krupkova et al, 2016a ). Based on this concern, a team produced large quantities of gelatin microspheres loaded with EGCG by a modified electrospray technique and systematically validated them in vitro ( Loepfe et al, 2019 ). Coculture with IVD cells in 3D alginate constructs showed that EGCG-GM had excellent biocompatibility and significantly inhibited the expression of IL-1β-induced inflammatory factors (IL-6, IL-8, and COX-2) and catabolic mediators (MMP-1, -3, and -13).…”

Repair Strategies and Bioactive Functional Materials for Intervertebral Disc

“…In summary, EGCG encapsulation based on electrospraying leads to microparticle cytocompatibility that preserves EGCG activity and shows potential for controlling EGCG release by downregulating localized inflammation. [125] Liu et al developed an aspirin (ASP)-loaded hydrogel by mixing ASP-liposomes with photocrosslinkable gelatin-methacryloyl (GelMA; together termed ASP-Lip@GelMA). The ASP-Lip@GelMA hydrogel upregulated aggrecan and collagen II, whereas decreased ADAMTS reduced MMPs by restraining HMGB-1 release.…”