Release Of Epigallocatechin Gallate Research Articles

Design and development of surface modified epigallocatechin 3-gallate NanoCubogel for localized delivery to oral submucous fibrosis therapy

The present study is aimed at the development of stearylamine (SA) modified epigallocatechin 3-gallate (EGCG) loaded NanoCubes incorporated in mucoadhesive hydrogel (NanoCubogel), for the local treatment of oral submucous fibrosis (OSF) owing to its anti-fibrotic, anti-inflammatory, and oxygen radical scavenging properties with a better safety profile. The prepared NanoCubes and mucoadhesive NanoCubogel were evaluated and characterized for various parameters including in-vitro release and ex-vivo permeation studies. The optimized NanoCubes had a particle size, polydispersity index, zeta potential, and entrapment efficiency of 140.3 ± 1.12 nm, 0.173 ± 0.08, 46.9 ± 1.69 mV, and 59.0 ± 1.73%, respectively with cube-shaped morphology. The viscosity of the NanoCubogel was found to be 9253 ± 112 cps. The SA modified NanoCubogel showed slower and sustained release of EGCG with higher permeation across buccal mucosa when compared to that of unmodified and pure EGCG. The formulation was found to be stable during the storage period. The developed NanoCubogel was capable of getting retained at the diseased site for a longer duration and releasing the EGCG locally for the desired time. Thus, the developed formulation may be used as an alternative treatment for OSF.

Methacrylation of epigallocatechin-gallate for covalent attachment with a dental polymer

ObjectiveSynthesize novel epigallocatechin-gallate (EGCG) methacrylate monomers with the ability to copolymerize with dental methacrylate resins. MethodsEGCG was reacted with 1/3 (E33), 2/3 (E67) and 1 (E100) molar equivalents of methacyloyl chloride introducing three degrees of polymerizablility. EGCG-methacrylates were characterized by Fourier Transform Infrared Spectroscopy (FTIR) and Nuclear Magnetic Resonance (NMR). E33, E67, E100 and neat EGCG were incorporated into TEGDMA at 0.5–20% ratios (m/m). Copolymers were tested for degree of conversion (%DC), EGCG release, gel content (%GC), degree of swelling (%DS), flexural properties and bacterial viability (Streptococcus mutans, baseline/30-days). Neat TEGDMA and TEGDMA passively loaded with EGCG (E0) were used as controls. Data were analysed by one-way ANOVA, Tukey, and Dunnett’s method (α=5%). Two-way ANOVA and Bonferroni were used to investigate factor interaction. ResultsFTIR/NMR confirmed synthesis of desired compounds. All of E100 incorporated ratios had %DC similar to TEGDMA. Remaining groups had reduction in %DC at 2% in E0, 10% in E33 and 20% in E67 ratios. EGCG was stable within ECGC-methacrylate copolymers. Release of EGCG from E0 significantly increased with higher EGCG ratios. Except for E100, higher EGCG or EGCG-methacrylate ratios led to decreased %CG and %DS. At baseline, E0 had the lowest bacterial survival rates (1–10% survival) at all ratios compared to E33, E67, E100, and neat TEGDMA. However, E33, E67 and E100 still had statistically lower survival rates (7–53%) compared with neat TEGDMA. After 30-days, all compounds had similar survival rates for all ratios, which were lower than that of neat TEGDMA. SignificanceDemonstration of methacrylate functionalized EGCG- with inherited antibacterial activity for improved restoration longevity.

A Tumor-Specific Ferric-Coordinated Epigallocatechin-3-gallate cascade nanoreactor for glioblastoma therapy

IntroductionNumerous options for treatment of glioblastoma have been explored; however, single-drug therapies and poor targeting have failed to provide effective drugs. Chemotherapy has significant antitumor effect, but the efficacy of single-drug therapies in the clinic is limited over a long period of time. Thus, novel therapeutic approaches are necessary to address these critical issues. ObjectivesThe present study, we investigated a tumor-specific metal-tea polyphenol-based cascade nanoreactor for chemodynamic therapy-enhanced chemotherapy. MethodsHA-EGCG was synthesized for the first time by introducing epigallocatechin-3-gallate (EGCG) into the skeleton of hyaluronic acid (HA) with reducible disulfide bonds. A rapid and green method was developed to fabricate the metal-tea polyphenol networks (MTP) with an HA-EGCG coating (DOX@MTP/HA-EGCG) based on Fe3+ and EGCG for targeted delivery of doxorubicin hydrochloride (DOX). GL261 cells were used to evaluate the antitumor efficacy of the DOX@MTP/HA-EGCG nanoreactor in vitro and in vivo. ResultsDOX@MTP/HA-EGCG nanoreactors were able to disassemble, resulting in escape of their components from lysosomes and precise release of DOX, Fe3+, and EGCG in the tumor cells. HA-EGCG depleted glutathione to amplify oxidative stress and enhance chemodynamic therapy. The results of in vivo experiments suggested that DOX@MTP/HA-EGCG specifically accumulates at the CD44-overexpressing GL261 tumor sites and that sustained release of DOX and Fe3+ induced a distinct therapeutic outcome. ConclusionsThe findings suggested the developed nanoreactor has promising potential as a future GL261 glioblastoma therapy.

Preparation and characterization of octenyl succinylated starch microgels via a water-in-oil (W/O) inverse microemulsion process for loading and releasing epigallocatechin gallate

Corn starch (CS), octenyl succinic anhydride modified corn starch (OSCS) and shells (OSCs) microgels have been prepared using water-in-oil (W/O) inverse microemulsions for loading and releasing of epigallocatechin gallate (EGCG). The structural and morphological properties of CS, OSCS, and OSCs microgels were characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), and Thermogravimetric analysis (TGA). The strong hydrogen bonds between starch molecules in the W/O system and interplay between hydroxyl groups of EGCG and oxygen atoms of starch microgels were formed. OSCs microgel showed low average particle size and weak thermal stability with an irregular shape and a typical V-type crystalline structure. Encapsulation efficiency (EE) and clearance rate of 2,2-diphenyl-1-picrylhydrazyl (DPPH) for EGCG were ranged between 41.78 and 63.89% and 75.53–85.37%, respectively, when absorbed into OSCS and OSCs microgels, the values which were higher than that of CS microgel. Further, OS starch microgels (particularly OSCs) modulated the slow release of EGCG into simulated gastrointestinal tract conditions and therefore could be proposed as an encapsulating agent for loading polyphenols.

Enhancing antioxidant, antimicrobial and anti‐NSCLC activities of (‐)‐epigallocatechin gallate encapsulated poly(butyl‐2‐cyanoacrylate) nanowires applications in dietary supplements

Summary(‐)‐Epigallocatechin gallate (EGCG) exhibits multiple biological activities, but unfortunately with poor stability. Poly(butyl‐2‐cyanoacrylate) (PBCA) nanoparticles have been widely elaborated for nearly 50 years. However, PBCA‐based nanowires (PNWs) were reported scarcely. Here, EGCG‐encapsulated PNWs (EGCG@PNWs) were successfully constructed. Employing PNWs as a delivery material, 2.0 mg EGCG into oil phase as optimum allocation was encapsulated in PNWs, forming EGCG@PNWs with the particle sizes of about 200 nm in diameter and 4 μm in length, encapsulation efficiency of about 93.96 ± 3.01%, and the zeta potential more than −30 mV. Further, the slower EGCG release from EGCG@PNWs (Oil) in 95% ethanol fatty simulant exhibited higher antioxidant activity than that of 50% ethanol. The antibacterial activities against E. coli and S. aureus and the growth inhibition effects on non‐small‐cell lung cancer (NSCLC) were also enhanced. Results revealed that EGCG@PNWs can be used as dietary supplements to enhance antioxidant, antibacterial and anti‐NSCLC effects.

Chitosan-PEG-folate-Fe(III) complexes as nanocarriers of epigallocatechin–3–gallate

Controlled release nanocarriers systems are promising for the administration of epigallocatechin–3–gallate (EGCG) in the treatment and prevention of several diseases. Therefore, the stability and therapeutic effects of EGCG must be enhanced from an encapsulation strategy. Thus, this research aims to explore a method to prepare EGCG nanocarriers based on coordination complexes from Fe (III) ions and blends of modified chitosan (Ch) with polyethylene glycol (PEG) and folic acid (F). Different degrees of deacetylated Ch and conjugated with F were evaluated, whose values determined the final amount of Fe (III) in the complexes. All these complexes were amorphous with a polydispersity index (PDI) higher than 0.3. The assembling and homogeneity were improved adding tripolyphosphate (TPP), yielding particle sizes near 200 nm, and PDI values of 0.2, measured by DLS and TEM. The EGCG encapsulation efficiency was about 60%, and the loading capacity was in the range of 26% to 50%. The EGCG release profile displayed a controlled release without a burst effect, providing the best fit with the Korsmeyer-Peppas model, indicating interactions among EGCG and the polymer matrix. The above results reveal the potential of these nanocarriers as suitable systems for controlled release and have not yet been reported.

“Ferrero-like” nanoparticles knotted injectable hydrogels to initially scavenge ROS and lastingly promote vascularization in infarcted hearts

Myocardial infarction (MI) exhibits a complicated and ever-accelerated pathological change involving excessive reactive oxygen species (ROS) and the up-regulation of pro-inflammatory cytokines in the initial stage, and a permanently inadequate blood supply. Herein, an injectable hydrogel fabricated by nanoparticles (NPs) knotted thiolated hyaluronic acid (HA-SH) was reported to reverse the hostile microenvironment and rebuild the heart functions after MI Inspired by the composite shell-core structure of Ferrero chocolate sphere, a mimetic nanocarrier was designed to consist of the hydrophobic dimethyloxalylglycine (DMOG) NPs core and a thick polydopamine (PDA) shell formed by the self-polymerization of dopamine embedded with water-soluble drug epigallocatechin-3-gallate (EGCG) through π-π interactions. The resulted “Ferrero-like” NPs exhibited a “three-in-one” capacity, namely loading two distinct drugs, elimination of ROS, and serving a crosslinker to knot HA-SH. “Ferrero-like” NPs and HA-SH could rapidly form a hydrogel that exhibited a stable mechanical property, high capability to capture ROS, and programmed release of EGCG and DMOG. Four weeks after deploying the “Ferrero-like” NPs knotted hydrogels into rat infarcted hearts, the ejection fraction (EF) increased by 23.7%, and the infarct size decreased by 21.1%, and the fibrotic area reduced by 24.4%. The outcomes of immunofluorescence staining and reverse transcription-polymerase chain reaction (RT-PCR) demonstrated a down-regulation of inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interferon-γ (IFN-γ)), up-regulation of vascular related growth factors (hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGFA), von Willebrand factor (vWF), angiopoietin-1 (Ang-1)) and cardiac-related mRNAs (gap junction protein (C×43), Cadherin 2). All in all, in this report, a very simple approach to intertemporally address the intricate and ongoing pathological changes after MI by injecting “Ferrero-like” NPs knotted hydrogels is developed to reverse hostile microenvironment, with an ability to scavenge ROS, down-regulate pro-inflammation factors in the first stage, and promote angio-genesis in a long term, thereby contributing to a significant improvement of heart functions.

A smart and active film with tunable drug release and color change abilities for detection and inhibition of bacterial growth.

Antimicrobial resistance has become a global issue and thus the development of natural products/biomedical materials composites with antibacterial activities is urgently needed. When acute wounds develop into chronic wounds, the wound environments become alkaline. As long as infections occur, the wound pH further increases, making the wounds difficult to heal. Besides, bacterial growth in poultry, meat, fish and seafood products is usually reflected in a marked increase of pH values. Herein, smart, stimuli responsive self-assembled multilayer and complex film were constructed through the formation of hydrogen bonds and hydrophobic interactions between hydroxypropyl methylcellulose (HPMC) and epigallocatechin-3-gallate (EGCG), thereby greatly reducing the hydrophilicity of HPMC and offering enhanced mechanical strength, superior free radical scavenging capability, and improved water vapor and light barrier properties. The EGCG/HPMC complex film was able to control EGCG release by tuning pH or temperature of the release medium. Furthermore, incorporation of CuS nanoparticles into the film allowed it to triggers EGCG release in an on-demand fashion under near-infrared (NIR) exposure. Bacterial growth in glucose-free nutrient broth medium caused pH to rise (near pH8.0), leading to transformation of EGCG from phenol type to phenolate ion and then quinone, allowing for spontaneous generation of H2O2 to kill bacteria. The complex films changed their color in response to bacterial growth because EGCG transformed from phenol type to quinone type under alkaline condition. The green synthesized EGCG/HPMC complex films can be used as a colorimetric pH indicator and an antibacterial material for wound dressing and food packaging applications.

In vitro augmentation of chondrogenesis by Epigallocatechin gallate in primary Human chondrocytes - Sustained release model for cartilage regeneration

Epigallocatechin-3-gallate (EGCG), a plant polyphenol catechin is potent chondrogenic drug which enhances cartilage regeneration. Hence, sustained release of EGCG from interlinked porous polycaprolactone (PCL) scaffolds can be beneficial in engineering a cartilage construct. In this study, 10% (w/v) and 12% (w/v) PCL scaffold were fabricated by incorporation of 2 different concentrations (1 mg/ml & 2 mg/ml) of EGCG loaded albumin nanoparticles (ENP). Morphological analysis of the fabricated scaffolds with Field emission scanning electron microscope (FESEM) revealed interlinked porous structures (pore size range 50 μm–300 μm) with embedded ENP on the scaffolds surface. In addition, the ENP synthesized by desolvation technique were spherical in shape with diameters in the range of 110 nm–210 nm. Further, X-ray diffraction of ENP and scaffolds implied amorphization of EGCG which is highly preferred in drug delivery application. Moreover, spectroscopic analysis with Fourier Transform Infrared (FTIR) and Raman spectrophotometry confirmed incorporation of ENP into scaffolds and chemical stability of PCL and EGCG during fabrication. Importantly, all groups showed sustained release for 22 days and non fickian diffusion through scaffolds. The drug release data also inferred that the concentration of ENP modulated EGCG release from scaffolds. Furthermore, in vitro chondrogenic study with Human chondrocytes for 21 days revealed significant increase in glycosaminoglycan deposition under the influence of EGCG. All these results suggest that ENP loaded polycaprolactone scaffolds, with intrinsic ability for releasing EGCG in a sustained fashion can serve as a prospective matrix in cartilage engineering.

Preparation of debranched starch nanoparticles by ionic gelation for encapsulation of epigallocatechin gallate

Starch nanoparticles are promising candidates for the delivery of active compounds or drugs. The purpose of this study was to prepare nanoparticles from debranched starch using an ionic gelation method. Negatively charged carboxymethyl debranched starch (CMDBS) was obtained by modification of debranched starch (DBS). The zeta potential value of CMDBS with a degree of substitution of 0.81 was approximately −26 mV. The starch nanoparticles formed from 2 mg mL−1 CMDBS and cationized DBS (CDBS) had particle sizes of 50 to 100 nm, as determined by transmission electron spectroscopy, and most nanoparticles were spherical in shape. Measurements with a quartz crystal microbalance with dissipation monitoring confirmed a successful adsorption interaction between the negatively charged CMDBS and positively charged CDBS. Epigallocatechin gallate (EGCG) was successfully incorporated into the nanoparticles with the highest encapsulation efficiency of 84.4%, and the resulting nanoparticles showed controlled release of EGCG into simulated gastric and intestinal fluids.

Enhancement of the permeability and activities of epigallocatechin gallate by quaternary ammonium chitosan/fucoidan nanoparticles

Epigallocatechin gallate (EGCG) has many biological functions; however, the use of EGCG in biomedical and food industries was limited due to its poor oral absorption and high susceptibility to degradation. In this study, a mucoadhesive quaternary chitosan was synthesized and combined with fucoidan (FD) (or depolymerized lower molecular weight fucoidan, LMWF) to prepare EGCG-loaded nanoparticles, which extended EGCG release over 300 min and enhanced the transepithelial permeation of EGCG using Caco-2 cells as a model for intestinal absorption. The nanoparticls protected EGCG against degradation in phosphate buffer (pH 6.8) and the remaining EGCG was 1.7-folds higher than the control (EGCG alone). The additive effects of EGCG combined with FD or LMWF in the nanoparticles increased the DPPH radical scavenging activity and the enzyme inhibitory activity against α-amylase (2.82–4.92 fold increase) and α-glucosidase (1.35–1.67 fold increase), while quaternary chitosan helped to enhance the antibacterial effect of EGCG.

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

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.

Pharmacokinetic, toxicokinetic, and bioavailability studies of epigallocatechin-3-gallate loaded solid lipid nanoparticle in rat model

Epigallocatechin-3-gallate (EGCG), derived from green tea, is an active phytochemical against many types of cancer, cardiovascular, neurological and inflammatory diseases. However, its pharmaceutical activity is limited due to low bioavailability and chemical instability. To overcome these limitations, we fabricated spherical, EGCG loaded solid lipid nanoparticles (SLN-EGCG) as an oral delivery system. The SLN-EGCG showed a hydrodynamic diameter of 300.2 ± 3.8 nm with the drug encapsulation efficiency of 81 ± 1.4%. Additionally, a slow and sustained release of EGCG was noted. Mathematical modeling of release kinetic data suggested that the SLN-EGCG followed the Higuchi model and released EGCG via fickian diffusion method. The data on pharmacokinetic parameters indicated significantly improved bioavailability and protection of EGCG from degradation due to encapsulation into SLN. The SLN-EGCG did not show any acute or sub-chronic toxicity when compared with free EGCG in the rat model. Together these data supported the hypothesis that SLN-EGCG is capable of enhancing the bioavailability and stability of EGCG and can be used as an alternative system for oral administration of EGCG.

Encapsulation of epigallocatechin-3-gallate into albumin nanoparticles improves pharmacokinetic and bioavailability in rat model.

In the present study, we fabricated epigallocatechin-3-gallate (EGCG) loaded albumin nanoparticles (Alb-NP-EGCG) to enhance bioavailability and improve pharmacokinetic parameters of EGCG. The physicochemical properties of the Alb-NP-EGCG were studied using scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction and in vitro release studies. Characterization of Alb-NP-EGCG indicated the formation of spherical nanoparticles with no drug and excipient interaction. Alb-NP-EGCG showed a high drug loading capacity of 92%. Further, in vitro study showed a sustained release of EGCG from Alb-NP-EGCG over a period of 48h. Mathematical modeling and release kinetics indicated that the Alb-NP-EGCG followed zero order kinetic and EGCG was released via fickian diffusion method. In vivo bioavailability and distribution of Alb-NP-EGCG showed an enhanced plasma concentration of EGCG with 1.5 fold increase along with prolonged T 1/2 of 15.6h in the system when compared with the free EGCG. All this study demonstrated the fabrication of EGCG loaded albumin nanoparticles which favored the slow and sustained release of EGCG with improved pharmacokinetics and bioavailability thereby prolonging the action of EGCG. Additional acute and sub-acute toxicity test of the Alb-NP-EGCG demonstrated the safety of the Alb-NP-EGCG. Therefore, the Alb-NP-EGCG could be a promising drug delivery system for EGCG.

Lipase‐catalyzed synthesis of epigallocatechin gallate‐based polymer for long‐term release of epigallocatechin gallate with antioxidant property

ABSTRACTEpigallocatechin gallate (EGCG) must be released in a controlled manner in order to maximize its long‐term potential as an antioxidant. In this study, lipase‐catalyzed polymerization of EGCG with divinyl adipate and sugar alcohols was conducted to form polyEGCG, which enables long‐term controlled release of EGCG via hydrolysis of ester linkages. The polymer yields were influenced by monomer ratios, volume of solvent, and lipase concentration. EGCG was gradually released from polyEGCG under a physiological condition as ester groups of polyEGCG degraded over a period of more than two months, and the releasing rate was influenced by the type of the sugar alcohols and EGCG ratios. EGCG released from polyEGCG maintained its antioxidant activity and the cell viability of polyEGCG eluent with polymer concentration higher than 0.05 mg/mL was as high as 100%. These results indicate that polyEGCG has potential application as a highly efficient and long‐term antioxidative material with low cytotoxicity. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47693.

Development of casein-based nanoencapsulation systems for delivery of epigallocatechin gallate and folic acid.

In this work, binding characteristics of two hydrophilic nutraceutical models, namely epigallocatechin gallate (EGCG) and folic acid (FA), to sodium caseinate were studied by fluorimetry technique. EGCG‐loaded casein molecules were then converted to either re‐combined casein micelles (r‐CMs) or casein nanoparticles (CNPs). Binding stoichiometry of EGCG and FA was 0.81 and 1.02, respectively. As determined by DLS technique, the average particle size of r‐CMs prepared at 0.5% concentration was 66.2 nm. Thermal treatment (74°C, 20 s) had significant (p < 0.05) influence on the particle size of nanocarriers, but not nutraceutical loading. The average size of CNPs was larger than that of r‐CMs. The encapsulation efficiency (EE) of EGCG was 85%, and its ejection from the nanocarrier was less than 3% over 21 days. Alkaline conditions resulted in higher release of EGCG than acidic conditions. r‐CMs were more effective than CNPs during the protection of EGCG against heat‐induced degradation. TEM micrographs confirmed the formation of r‐CMs.

Single Local Injection of Epigallocatechin Gallate-Modified Gelatin Attenuates Bone Resorption and Orthodontic Tooth Movement in Mice.

Osteoclastic bone resorption enables orthodontic tooth movement (OTM) in orthodontic treatment. Previously, we demonstrated that local epigallocatechin gallate (EGCG) injection successfully slowed the rate of OTM; however, repeat injections were required. In the present study, we produced a liquid form of EGCG-modified gelatin (EGCG-GL) and examined the properties of EGCG-GL with respect to prolonging EGCG release, NF-E2-related factor 2 (Nrf2) activation, osteoclastogenesis inhibition, bone destruction, and OTM. We found EGCG-GL both prolonged the release of EGCG and induced the expression of antioxidant enzyme genes, such as heme oxygenase 1 (Hmox1) and glutamate-cysteine ligase (Gclc), in the mouse macrophage cell line, RAW264.7. EGCG-GL attenuated intracellular reactive oxygen species (ROS) levels were induced by the receptor activator of nuclear factor-kB ligand (RANKL) and inhibited RANKL-mediated osteoclastogenesis in vitro. An animal model of bone destruction, induced by repeat Lipopolysaccharide (LPS)-injections into the calvaria of male BALB/c mice, revealed that a single injection of EGCG-GL on day-1 could successfully inhibit LPS-mediated bone destruction. Additionally, experimental OTM of maxillary first molars in male mice was attenuated by a single EGCG-GL injection on day-1. In conclusion, EGCG-GL prolongs the release of EGCG and inhibits osteoclastogenesis via the attenuation of intracellular ROS signaling through the increased expression of antioxidant enzymes. These results indicate EGCG-GL would be a beneficial therapeutic approach both in destructive bone disease and in controlling alveolar bone metabolism.

A Poloxamer-407 modified liposome encapsulating epigallocatechin-3-gallate in the presence of magnesium: Characterization and protective effect against oxidative damage

Epigallocatechin-3-gallate (EGCG) is a polyphenolic catechin from green tea, well known for being bioactive in age-associated pathologies where oxidative stress plays a preeminent role. The activity of this molecule is however contrasted by its high chemical and metabolic instability that determines a poor concentration of the antioxidant within the biological system after administration. In order to protect the molecule and increase its delivery efficiency, we have encapsulated EGCG inside anionic liposomes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine and cholesteryl hemisuccinate. To maximize EGCG internalization, magnesium salt was added in the preparation. However stable nanodispersions suitable for drug delivery were obtained only after treatment with Poloxamer-407, a polyethylene–propylene glycol copolymer. The structural and morphological properties of the produced dispersion were studied by X-ray diffraction, which showed a multilamellar structure even after EGCG addition and an ordering effect of Poloxamer-407; Dynamic Light Scattering demonstrated serum stability of the liposomes. The characterization was completed by evaluating both encapsulation efficiency (100%, in the final formulation) and in vitro EGCG release. Since oxidative stress is involved in numerous retinal degenerative diseases, such as age-related macular degeneration, the ability of these liposomes to contrast H2O2-induced cell death was assessed in human retinal cells. Morphological changes at the subcellular level were analyzed by Transmission Electron Microscopy, which showed that mitochondria were better preserved in cells treated with liposomes then those treated with free EGCG. In conclusion, the results demonstrated that the produced formulation enhances the efficacy of EGCG under stress conditions, thus representing a potential formulation for the intracellular delivery of EGCG in diseases caused by oxidative damage.

Green Fabrication of Ovalbumin Nanoparticles as Natural Polyphenol Carriers for Ulcerative Colitis Therapy

Nanoparticles (NPs) have the capacity to improve the bioactivity and bioavailability of anti-inflammatory drugs. Here, a green drug nanocarrier based on ovalbumin (OVA) was facilely produced via a self-assembling process by adding epigallo-catechin 3-gallate (EGCG) aqueous solution to OVA aqueous solution at 80 °C. The obtained EGCG-NPs had an average hydrodynamic diameter (around 202.9 nm), negative surface charge (approximately −13.2 mV), high EGCG encapsulation efficiency (98.1%), and reduction-responsive EGCG release capacity. Additionally, they possessed excellent biocompatibility and achieved a much higher cellular uptake rate of EGCG than pristine EGCG. Furthermore, EGCG-NPs had remarkably stronger capacity to suppress the secretion of pro-inflammatory mediators (e.g., tumor necrosis factor α, interleukin-6, interleukin-12) and promote the production of anti-inflammatory factor (interleukin-10), in comparison with pristine EGCG. Finally, in vivo experiments demonstrated the excellent therapeutic ef...

Comparative study in physico-chemical properties of gelatin derivatives and their microspheres as carriers for controlled release of green tea's extract

Two types of gelatin derivatives were prepared from type A and type B gelatin, respectively. Cationized gelatin was produced by conjugation of ethylenediamine into type A gelatin using carbodiimide reaction. Anionized gelatin was produced by conjugation of succinic anhydride to type B gelatin. Characteristics of four gelatin types and their microspheres fabricated by water-in-oil emulsion and glutaraldehyde crosslinking were evaluated. Cationized gelatin showed the highest positive charge and free amino group concentration due to the ethylenediamine conjugation, resulting in the highest crosslinking percentage and slowest degradation rate of cationized gelatin microspheres. Type A, B and anionized gelatin which had lower concentration of free amino groups produced the low crosslinking and fast-degrading microspheres. These gelatin microspheres were introduced as carrier for controlled release of epigallocatechin 3-gallate (EGCG), a high antioxidant green tea's extract. The cationized gelatin microspheres showed prolonged release of EGCG due to the slow degradation and ionic attraction with the negative-charged EGCG. The release of EGCG from type A, B and anionized gelatin microspheres was accelerated as a result of diffusion and microsphere's swelling mechanisms. These EGCG-loaded gelatin microspheres can be further studied as injectable drug for localized treatment of inflammation-related diseases with minimal invasion.