Publications by authors named "Didier Merlin"

174 Publications

Micro- and nanotechnological delivery platforms for treatment of dysbiosis-related inflammatory bowel disease.

Nanomedicine (Lond) 2021 Jul 1. Epub 2021 Jul 1.

Institute for Biomedical Sciences, Center for Inflammation, Immunity & Infection, Digestive Disease Research Group, Georgia State University, Atlanta, GA 30302, USA.

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http://dx.doi.org/10.2217/nnm-2021-0167DOI Listing
July 2021

Intestinal iron absorption is appropriately modulated to match physiological demand for iron in wild-type and iron-loaded Hamp (hepcidin) knockout rats during acute colitis.

PLoS One 2021 18;16(6):e0252998. Epub 2021 Jun 18.

Food Science & Human Nutrition Department, University of Florida, Gainesville, FL, United States of America.

Mucosal damage, barrier breach, inflammation, and iron-deficiency anemia (IDA) typify ulcerative colitis (UC) in humans. The anemia in UC appears to mainly relate to systemic inflammation. The pathogenesis of this 'anemia of inflammation' (AI) involves cytokine-mediated transactivation of hepatic Hamp (encoding the iron-regulatory hormone, hepcidin). In AI, high hepcidin represses iron absorption (and iron release from stores), thus lowering serum iron, and restricting iron for erythropoiesis (causing anemia). In less-severe disease states, inflammation may be limited to the intestine, but whether this perturbs iron homeostasis is uncertain. We hypothesized that localized gut inflammation will increase overall iron demand (to support the immune response and tissue repair), and that hepatic Hamp expression will decrease in response, thus derepressing (i.e., enhancing) iron absorption. Accordingly, we developed a rat model of mild, acute colitis, and studied iron absorption and homeostasis. Rats exposed (orally) to DSS (4%) for 7 days had intestinal (but not systemic) inflammation, and biomarker analyses demonstrated that iron utilization was elevated. Iron absorption was enhanced (by 2-3-fold) in DSS-treated, WT rats of both sexes, but unexpectedly, hepatic Hamp expression was not suppressed. Therefore, to gain a better understanding of regulation of iron absorption during acute colitis, Hamp KO rats were used for further experimentation. The severity of DSS-colitis was similar in Hamp KOs as in WT controls. In the KOs, increased iron requirements associated with the physiological response to colitis were satisfied by mobilizing hepatic storage iron, rather than by increasing absorption of enteral iron (as occurred in WT rats). In conclusion then, in both sexes and genotypes of rats, iron absorption was appropriately modulated to match physiological demand for dietary iron during acute intestinal inflammation, but regulatory mechanisms may not involve hepcidin.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252998PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213193PMC
June 2021

Oral Administration of Ginger-Derived Lipid Nanoparticles and Dmt1 siRNA Potentiates the Effect of Dietary Iron Restriction and Mitigates Pre-Existing Iron Overload in KO Mice.

Nutrients 2021 May 15;13(5). Epub 2021 May 15.

Food Science & Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA.

Intestinal iron transport requires an iron importer (Dmt1) and an iron exporter (Fpn1). The hormone hepcidin regulates iron absorption by modulating Fpn1 protein levels on the basolateral surface of duodenal enterocytes. In the genetic, iron-loading disorder hereditary hemochromatosis (HH), hepcidin production is low and Fpn1 protein expression is elevated. High Fpn1-mediated iron export depletes intracellular iron, causing a paradoxical increase in Dmt1-mediated iron import. Increased activity of both transporters causes excessive iron absorption, thus initiating body iron loading. Logically then, silencing of intestinal Dmt1 or Fpn1 could be an effective therapeutic intervention in HH. It was previously established that Dmt1 knock down prevented iron-loading in weanling (encoding hepcidin) KO mice (modeling type 2B HH). Here, we tested the hypothesis that Dmt1 silencing combined with dietary iron restriction (which may be recommended for HH patients) will mitigate iron loading once already established. Accordingly, adult KO mice were switched to a low-iron (LFe) diet and (non-toxic) folic acid-coupled, ginger nanoparticle-derived lipid vectors (FA-GDLVs) were used to deliver negative-control (NC) or Dmt1 siRNA by oral, intragastric gavage daily for 21 days. The LFe diet reduced body iron burden, and experimental interventions potentiated iron losses. For example, Dmt1 siRNA treatment suppressed duodenal Dmt1 mRNA expression (by ~50%) and reduced serum and liver non-heme iron levels (by ~60% and >85%, respectively). Interestingly, some iron-related parameters were repressed similarly by FA-GDLVs carrying either siRNA, including Fe (as FeCl) absorption (~20% lower), pancreatic non-heme iron (reduced by ~65%), and serum ferritin (decreased 40-50%). Ginger may thus contain bioactive lipids that also influence iron homeostasis. In conclusion, the combinatorial approach of FA-GDLV and Dmt1 siRNA treatment, with dietary iron restriction, mitigated pre-existing iron overload in a murine model of HH.
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http://dx.doi.org/10.3390/nu13051686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157040PMC
May 2021

Atomic Force Microscopy to Characterize Ginger Lipid-Derived Nanoparticles (GLDNP).

Bio Protoc 2021 Apr 5;11(7):e3969. Epub 2021 Apr 5.

Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Digestive Disease Research Group, Georgia State University, Atlanta, GA, USA.

We have demonstrated that a specific population of ginger-derived nanoparticles (GDNP-2) could effectively target the colon, reduce colitis, and alleviate colitis-associated colon cancer. Naturally occurring GDNP-2 contains complex bioactive components, including lipids, proteins, miRNAs, and ginger secondary metabolites (gingerols and shogaols). To construct a nanocarrier that is more clearly defined than GDNP-2, we isolated lipids from GDNP-2 and demonstrated that they could self-assemble into ginger lipid-derived nanoparticles (GLDNP) in an aqueous solution. GLDNP can be used as a nanocarrier to deliver drug candidates such as 6-shogaol or its metabolites (M2 and M13) to the colon. To characterize the nanostructure of GLDNP, our lab extensively used atomic force microscopy (AFM) technique as a tool for visualizing the morphology of the drug-loaded GLDNP. Herein, we provide a detailed protocol for demonstrating such a process.
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http://dx.doi.org/10.21769/BioProtoc.3969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054207PMC
April 2021

PepT1-knockout mice harbor a protective metabolome beneficial for intestinal wound healing.

Am J Physiol Gastrointest Liver Physiol 2021 05 24;320(5):G888-G896. Epub 2021 Mar 24.

Institute for Biomedical Sciences, Digestive Diseases Research Group, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia.

Genetic knockout (KO) of peptide transporter-1 (PepT1) protein is known to provide resistance to acute colitis and colitis-associated cancer (CAC) in mouse models. However, it was unclear which molecule(s) or pathway(s) formed the basis for these protective effects. Recently, we demonstrated that the PepT1 microbiota is sufficient to protect against colitis and CAC. Given that PepT1 KO alters the gut microbiome and thereby changes the intestinal metabolites that are ultimately reflected in the feces, we investigated the fecal metabolites of our PepT1 KO mice. Using a liquid chromatography-mass spectrometry (LC-MS)-based untargeted-metabolomics technique, we found that the fecal metabolites were significantly different between the KO and normal wild-type (WT) mice. Among the altered fecal metabolites, tuberonic acid (TA) was sevenfold higher in KO mouse feces than in WT mouse feces. Accordingly, we studied whether the increased TA could direct an anti-inflammatory effect. Using in vitro models, we discovered that TA not only prevented lipopolysaccharide (LPS)-induced inflammation in macrophages but also improved the epithelial cell healing processes. Our results suggest that TA, and possibly other fecal metabolites, play a crucial role in the pathway(s) associated with the anticolitis effects of PepT1 KO. Fecal metabolites were significantly different between the KO and normal wild-type (WT) mice. One fecal metabolite, tuberonic acid (TA), was sevenfold higher in KO mouse feces than in WT mouse feces. TA prevented lipopolysaccharide (LPS)-induced inflammation in macrophages and improved the epithelial cell healing process.
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http://dx.doi.org/10.1152/ajpgi.00299.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202197PMC
May 2021

Toward Point-of-Care Diagnostics to Monitor MMP-9 and TNF-α Levels in Inflammatory Bowel Disease.

ACS Omega 2021 Mar 3;6(10):6582-6587. Epub 2021 Mar 3.

Department of Chemistry, Georgia State University, 788 Petit Science Center, Atlanta, Georgia 30302, United States.

We have investigated the association of matrix metallopeptidase 9 (MMP-9) and tumor necrosis factor α (TNF-α) levels with colitis severity using an established IL10-/- mouse model, which reflects the severity of inflammation in humans with inflammatory bowel disease (IBD). We found that MMP-9 and TNF-α correlated with colitis severity. In parallel, we developed assays to detect fecal MMP-9 and serum TNF-α using "cap and release" mesoporous silica nanoparticles (MSNs). MMP-9 peptide substrates as "caps" were attached to dye-loaded MSNs. The introduction of MMP-9 resulted in substrate cleavage and subsequent dye release, which was rapidly detected using a fluorometer. For TNF-α, an anti-TNF antibody was used as the "cap". The introduction of TNF-α antigen leads to the release of the dyes because the antigen binds more strongly to the antibody cap. The MSN-based assays can detect MMP-9 and TNF-α effectively, although signal amplification is required to meet clinical sensitivity.
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http://dx.doi.org/10.1021/acsomega.0c05115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970462PMC
March 2021

Point-of-Care Monitoring of Colitis Using Intestinal Alkaline Phosphatase in Inflammatory Bowel Disease.

ACS Sens 2021 03 26;6(3):698-702. Epub 2021 Feb 26.

Department of Chemistry, Georgia State University 788 Petit Science Center, Atlanta, Georgia 30302, United States.

Intestinal Alkaline Phosphatase (IAP) was investigated as a potential biomarker to monitor colitis in a mouse model of Inflammatory Bowel Disease (IBD). We developed a Point-Of-Care (POC) assay to detect IAP with a glucose meter in 15 min. We synthesized a paracetamol-bearing compound specifically cleaved by IAP to release paracetamol, which can be detected with a personal glucometer. Interleukin 10 deficient (IL 10-/-) mouse model samples were used to compare the IAP level in mice with mild or severe colitis. The results showed that fecal IAP level was significantly lower in each mouse sample with severe colitis than with mild colitis. Mice treated with anti-Tumor Necrosis Factor-alpha (anti-TNF-α) to decrease inflammation exhibited a much higher level of IAP than those without treatment (IAP levels from anti-TNF-α treated vs nontreated = 2.80 U vs 0.11 U, < 0.0001). Taken together, IAP can be considered as a potential biomarker to monitor colitis, and a rapid, user-friendly POC glucometer-based assay can be potentially used to monitor colitis levels and inflammation flareups in IBD.
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http://dx.doi.org/10.1021/acssensors.0c02177DOI Listing
March 2021

IL-36R signaling integrates innate and adaptive immune-mediated protection against enteropathogenic bacteria.

Proc Natl Acad Sci U S A 2020 11 21;117(44):27540-27548. Epub 2020 Oct 21.

Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303;

Enteropathogenic bacterial infections are a global health issue associated with high mortality, particularly in developing countries. Efficient host protection against enteropathogenic bacterial infection is characterized by coordinated responses between immune and nonimmune cells. In response to infection in mice, innate immune cells are activated to produce interleukin (IL)-23 and IL-22, which promote antimicrobial peptide (AMP) production and bacterial clearance. IL-36 cytokines are proinflammatory IL-1 superfamily members, yet their role in enteropathogenic bacterial infection remains poorly defined. Using the enteric mouse pathogen, , we demonstrate that signaling via IL-36 receptor (IL-36R) orchestrates a crucial innate-adaptive immune link to control bacterial infection. IL-36R-deficient mice ( ) exhibited significant impairment in expression of IL-22 and AMPs, increased intestinal damage, and failed to contain compared to controls. These defects were associated with failure to induce IL-23 and IL-6, two key IL-22 inducers in the early and late phases of infection, respectively. Treatment of mice with IL-23 during the early phase of infection rescued IL-22 production from group 3 innate lymphoid cells (ILCs), whereas IL-6 administration during the late phase rescued IL-22-mediated production from CD4 T cell, and both treatments protected mice from uncontained infection. Furthermore, IL-36R-mediated IL-22 production by CD4 T cells was dependent upon NFκB-p65 and IL-6 expression in dendritic cells (DCs), as well as aryl hydrocarbon receptor (AhR) expression by CD4 T cells. Collectively, these data demonstrate that the IL-36 signaling pathway integrates innate and adaptive immunity leading to host defense against enteropathogenic bacterial infection.
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http://dx.doi.org/10.1073/pnas.2004484117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959549PMC
November 2020

Highly Biocompatible Functionalized Layer-by-Layer Ginger Lipid Nano Vectors Targeting P-selectin for Delivery of Doxorubicin to Treat Colon Cancer.

Adv Ther (Weinh) 2019 Dec 18;2(12). Epub 2019 Sep 18.

Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Digestive Disease Research Group, Georgia State University, Atlanta, Georgia, 30302, United States.

A biocompatible natural nanoparticle drug delivery system that has specific cancer-targeting function holds vast promise for cancer therapy. Here, a fucoidan/poly-lysine-functionalized layer-by-layer ginger-derived lipid vector (LbL-GDLV) was designed to target P-selectin (overexpressed by endothelial cells) and deliver a loaded drug into vascularized colon cancer. , LbL-GDLVs selectively bound to P-selectin, and the degradation of the fucoidan outer layer in a milieu similar to the cancer microenvironment resulted in rapid attachment of the cancer cell and internalization of the remaining positively charged poly-lysine coated-GDLVs. Upon enzymolysis of the poly-lysine layer inside the cancer cell, the GDLV core released loaded doxorubicin (Dox) which had the expected effects. bio-distribution studies showed that intravenously injected LbL-GDLVs exhibited enhanced accumulation at the vascularized tumor site (~ 4.4-fold higher than control vesicles), presumably due to P-selectin-mediated targeting plus the enhanced permeability and retention effect (EPR). In two animal models used to screen anti-cancer efficacy (Luc-HT-29 and HCT-116 xenografts), Dox-loaded LbL-GDLVs (LbL-GDLVs/Dox) significantly inhibited tumor growth and demonstrated much better therapeutic efficiency than free Dox. More importantly, LbL-GDLVs/Dox exhibited excellent biocompatibility, and LbL-GDLVs encapsulation largely reduced the cardiotoxicity of free Dox and avoided the notorious drug resistance of colon cells against free Dox. Together, these findings demonstrate the potential of our newly designed and highly biocompatible plant-derived LbL nanoparticles and their precise colon cancer drug delivery function.
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http://dx.doi.org/10.1002/adtp.201900129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546358PMC
December 2019

Matrix metalloproteinase 9 (MMP9) limits reactive oxygen species (ROS) accumulation and DNA damage in colitis-associated cancer.

Cell Death Dis 2020 09 17;11(9):767. Epub 2020 Sep 17.

Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States.

Colitis-associated cancer (CAC) is a subtype of colon cancer that is driven by chronic inflammation and is prevalent in chronic ulcerative colitis patients. The development of CAC is associated with the inflammation-dysplasia-carcinoma pathway which is significantly different than adenoma-carcinoma pathway of sporadic colon cancer (CRC). Matrix Metalloproteinase 9 (MMP9) is a zinc-dependent endopeptidase against extracellular matrix (ECM) proteins expressed in the gastrointestinal tract during inflammation. We have previously shown that MMP9 plays a tumor suppressor role in CAC via "MMP9-Notch1-ARF-p53 axis" pathway. The aim of this study is to determine the role of MMP9 in maintaining genomic stability in CAC. Homozygous transgenic mice with constitutive-expression of MMP9 in the colonic epithelium (TgM9) with their wild-type littermates (WT) and stably transfected HCT116 cells with/without MMP9 were used for in vivo and in vitro experiments, respectively. As 'proof of concept' model, nanoparticles (NPs) loaded with MMP9 siRNA were used to examine the effect of MMP9 silencing in the colonic epithelium. In CAC, colonic epithelium of TgM9 mice exhibited lower amounts of reactive oxygen species (ROS), less DNA damage, and increased expression of mismatch repair genes compared to WTs. Our study showed that MMP9 expression correlates with the reduced ROS levels, decreased DNA damage, and upregulated mismatch repair pathway. This suggests that MMP9 expression is a natural biological way to suppress CAC by limiting ROS accumulation and DNA damage in the colon. Therefore, MMP9 inhibition could be deleterious for CAC patient.
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http://dx.doi.org/10.1038/s41419-020-02959-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498454PMC
September 2020

Preparation and Characterization of Ginger Lipid-derived Nanoparticles for Colon-targeted siRNA Delivery.

Bio Protoc 2020 Jul;10(14)

Institute for Biomedical Science, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA.

Synthetic nanoparticle-based drug delivery system is widely known for its ability to increase the efficacy and specificity of loaded drugs, but it often suffers from relatively higher immunotoxicity and higher costs as compared to traditional drug formulations. Contrarily, plant-derived nanoparticles appear to be free from these limitations of synthetic nanoparticles; they are naturally occurring biocompatible vesicles that do not generate immunotoxicity and are easy to obtain. Additionally, lipids isolated from plant-derived nanoparticles have shown the capability of assembling themselves to spherical nano-sized liposomal particles. Herein, we employ lipids extracted from ginger-derived nanoparticles and load them with therapeutic siRNA (CD98-siRNA) to create CD98-siRNA/ginger-lipid nanoparticles. Characterization of the CD98-siRNA/ginger-lipid nanoparticles showed that they present a spherical shape, with a diameter of around 189.5 nm. The surface zeta potential of the nanoparticles varies from -18.1 to -18.4 mV. Furthermore, in recent research, the CD98-siRNA/ginger-lipid nanoparticles have shown specific colon targeting capability and excellent anti-inflammatory efficacy in a Dextran Sodium Sulfate (DSS) induced mouse model of colitis.
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http://dx.doi.org/10.21769/bioprotoc.3685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416531PMC
July 2020

Lipid-Based Drug Delivery Nanoplatforms for Colorectal Cancer Therapy.

Nanomaterials (Basel) 2020 Jul 21;10(7). Epub 2020 Jul 21.

Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Digestive Disease Research Group, Georgia State University, Atlanta, GA 30302, USA.

Colorectal cancer (CRC) is a prevalent disease worldwide, and patients at late stages of CRC often suffer from a high mortality rate after surgery. Adjuvant chemotherapeutics (ACs) have been extensively developed to improve the survival rate of such patients, but conventionally formulated ACs inevitably distribute toxic chemotherapeutic drugs to healthy organs and thus often trigger severe side effects. CRC cells may also develop drug resistance following repeat dosing of conventional ACs, limiting their effectiveness. Given these limitations, researchers have sought to use targeted drug delivery systems (DDSs), specifically the nanotechnology-based DDSs, to deliver the ACs. As lipid-based nanoplatforms have shown the potential to improve the efficacy and safety of various cytotoxic drugs (such as paclitaxel and vincristine) in the clinical treatment of gastric cancer and leukemia, the preclinical progress of lipid-based nanoplatforms has attracted increasing interest. The lipid-based nanoplatforms might be the most promising DDSs to succeed in entering a clinical trial for CRC treatment. This review will briefly examine the history of preclinical research on lipid-based nanoplatforms, summarize the current progress, and discuss the challenges and prospects of using such approaches in the treatment of CRC.
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http://dx.doi.org/10.3390/nano10071424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408503PMC
July 2020

Impact of PepT1 deletion on microbiota composition and colitis requires multiple generations.

NPJ Biofilms Microbiomes 2020 07 21;6(1):27. Epub 2020 Jul 21.

Institute for Biomedical Sciences, Center for Inflammation, Immunity and Infection, Digestive Disease Research Group, Georgia State University, Atlanta, GA, USA.

Numerous studies of knockout mice find impacts on microbiota composition that influence host phenotype. However, such differences can vanish when KO mice are compared directly to WT littermates, suggesting these differences do not reflect the genetic deletion per se but microbiota composition drifting over generations. Hence, our hypothesis that absence of di/tri-peptide transporter PepT1 altered microbiota composition resulting in resistance to colitis compelled scrutiny. In this study, we used PepT1 and WT founder mice bred separately for multiple generations. Such mice were then bred to each other to generate F1 PepT1 and WT littermates, which were then bred within their genotype to generate F2, F3, and F4, offspring. Here we report that founder PepT1 mice were, relative to their WT counterparts, resistant to DSS colitis. Such resistance was associated with alterations in gut microbiota, which, when transplanted to germfree mice, was sufficient to transfer resistance to colitis. Such differences were not observed when comparing F1 PepT1 to F1 WT littermates but rather, returned gradually over subsequent generations such that, relative to their F4 WT controls, F4 PepT1 displayed microbiota composition and colitis-resistant phenotype nearly identical to the founder PepT1 mice. Our findings indicate a role for PepT1 in influencing microbiota composition and, consequently, proneness to colitis and cancer. Overall, our study indicates that littermate-controlled experiments can be insufficient for assessing microbiota-dependent phenotypes and prevent a full comprehension of genotype-driven phenomena. Rather, impact of a single genetic alteration on microbiota and host phenotype may take generations to manifest.
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http://dx.doi.org/10.1038/s41522-020-0137-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374158PMC
July 2020

Genetically modified silk fibroin nanoparticles for drug delivery: preparation strategies and application prospects.

Nanomedicine (Lond) 2020 08 17;15(18):1739-1742. Epub 2020 Jul 17.

Institute for Biomedical Sciences, Center for Diagnostics & Therapeutics, Digestive Disease Research Group, Georgia State University, Atlanta, GA 30302, USA.

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http://dx.doi.org/10.2217/nnm-2020-0182DOI Listing
August 2020

Isolation and Characterization of Exosomes from Mouse Feces.

Bio Protoc 2020 Apr;10(8)

Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Digestive Disease Research Group, Georgia State University, Atlanta, Georgia, 30302, United States.

Exosomes secreted by colonic epithelial cells are present in feces and contain valuable epigenetic information, such as miRNAs, proteins, and metabolites. An in-depth study of this information is conducive to the diagnosis or treatment of relevant diseases. A crucial prerequisite of such a study is to establish an efficient isolation method, through which we can obtain a relatively more significant amount of exosomes from feces. This protocol is designed to effectively isolate a large number of exosomes from contaminants and other particles in feces by a combined method with fast filtration and sucrose density gradient ultracentrifugation. Exosomes generated by this method are suitable for further RNA, protein, and lipid analysis.
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http://dx.doi.org/10.21769/bioprotoc.3584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241525PMC
April 2020

Natural-lipid nanoparticle-based therapeutic approach to deliver 6-shogaol and its metabolites M2 and M13 to the colon to treat ulcerative colitis.

J Control Release 2020 07 23;323:293-310. Epub 2020 Apr 23.

Institute for Biomedical Sciences, Digestive Disease Research Group, Georgia State University, Atlanta, GA 30303, USA; Atlanta Veterans Affairs Medical Center, Decatur, GA 30302, USA.

The anti-inflammatory drug candidate, 6-shogaol, has demonstrated excellent efficacies in various in vitro studies. However, its rapid metabolism after oral administration results in poor bioavailability and undetectable in vivo pharmacokinetics. Here, we constructed a natural-lipid (NL) nanoparticle drug delivery system (NP-DDS) to encapsulate 6-shogaol and undertake its controlled release to the proposed drug target (colon). Our in vitro drug-release assay revealed that NL-encapsulated 6-shogaol (6-S-NL) exhibits a delayed drug-release profile compared to free 6-shogaol (free-6-S). Consistent with our expectations, orally administrated 6-S-NL exhibits a superior anti-inflammatory efficacy likely due to the controlled release compared to free 6-S in a dextran sulfate sodium (DSS)-induced mouse model of colitis. Although 6-S-NL treatment yields an enhanced concentration of 6-shogaol at the target site (colon), this concentration is still far below the effective level. We hypothesize that the released 6-shogaol undergoes rapid metabolism and that the metabolites of 6-shogaol may contribute to the anti-inflammatory efficacy of 6-S-NL. We thus examined the in vitro anti-inflammatory efficacies of two highly abundant colonic metabolites, M2 (a cysteine-conjugated metabolite) and M13 (a glutathione-conjugated metabolite), against macrophage cells. Reverse transcription-polymerase chain reaction (RT-PCR) data showed that both M2 and M13 (at 1.0 μg/mL) could down-regulate pro-inflammatory factors (TNF-α, IL-1β, and IL-6) and up-regulate an anti-inflammatory factor (IL-10) in inflamed Raw 264.7 cells. Subsequent in vitro wound-healing assays also confirmed that M2 and M13 accelerate the wound recovery process of Caco-2 cells at the concentrations seen in the colon (1.0 μg/mL). Further, in the DSS-induced mouse model of colitis, oral administration of M2- or M13-loaded NL nanoparticles (M2-NL, M13-NL) demonstrated excellent in vivo wound-healing effects, and these activities were better than those observed for 6-S-NL. Combined with the 6-S-NL's bio-distribution assay, our data show that: the 6-shogaol metabolites, M2 and M13, are more potent anti-inflammatory compounds than 6-shogaol itself; NL nanoparticles can effectively deliver 6-shogaol to the colon, with little accumulation seen in the kidney or liver; and the actions of M2 and M13 mostly confer the anti-inflammatory effect of 6-S-NL. Our results explained the discrepancy between the low tissue concentrations of NL delivered 6-shogaol and its effectiveness against ulcerative colitis (UC) in a mouse model. This study paved the way for further developing the NL-loaded active metabolites, M2 or M13, as novel targeted therapeutic approaches for curing UC.
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http://dx.doi.org/10.1016/j.jconrel.2020.04.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299768PMC
July 2020

Examination of food consumption in United States adults and the prevalence of inflammatory bowel disease using National Health Interview Survey 2015.

PLoS One 2020 23;15(4):e0232157. Epub 2020 Apr 23.

Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Center for Inflammation, Immunity and Infection, Digestive Disease Research Group, Georgia State University, Atlanta, Georgia, United States of America.

Various diets and food components have been implicated as one of the environmental factors associated with inflammatory bowel disease (IBD). Patients are often recommended nutritional guidelines to manage disease symptoms. However, the current food consumption pattern of US adults with IBD that are nationally representative is unclear. A secondary analysis of National Health Interview Survey 2015 was performed to characterize the estimated US adults with IBD and their food intake and consumption frequency using bivariate and multivariate logistic regression. Fries were consumed by a greater number of people with IBD. IBD population drank less 100% fruit juice and ate more cheese and cookies than non-IBD population. Intake of fries (OR 1.60, 95% CI 1.14-2.25) and sports and energy drinks (OR 1.46, 95% CI 1.07-1.97) and more frequent drinking of regular soda were significantly associated with the likelihood of having been told one have IBD, while popcorn (OR 0.73, 95% CI 0.548-0.971) and milk (OR 0.70, 95% CI 0.497-0.998) were associated with smaller odds, adjusting for covariates. Foods typically labeled as junk food were positively associated with IBD. Nonetheless, of the assessed 26 foods, we found eating patterns between IBD and non-IBD population to be mostly analogous. It is unclear whether the results reflect potential change in food intake in IBD population long before the survey interview. Understanding the role of food intake in IBD risk/prevalence would benefit from identifying other environmental factors (i.e. food desert), food processing (i.e. frying), and potential bioactive food components that can induce intestinal inflammation that can increase the individual's susceptibility to IBD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232157PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179926PMC
July 2020

Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives.

Int J Nanomedicine 2019 13;14:8875-8889. Epub 2019 Nov 13.

Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Digestive Disease Research Group, Georgia State University, Atlanta, GA 30302, USA.

Inflammatory bowel disease (IBD), which mainly consists of Crohn's disease and ulcerative colitis, is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The traditional treatment strategies relied on frequent administration of high dosages of medications, including antibiotics, non-steroidal anti-inflammatory drugs, biologics, and immunomodulators, with the goal of reducing inflammation. Some of these medications were effective in alleviating the early-stage inflammatory symptoms, but their long-term efficacies were compromised by the accumulation of toxicities. Recently, nanoparticle (NP)-based drugs have been widely studied for their potential to solve such problems. Various mechanisms/strategies, including size-, charge-, pH-, pressure-, degradation-, ligand-receptor-, and microbiome- dependent drug delivery systems, have been exploited in preclinical studies. A certain number of NP delivery systems have sought to target drugs to the inflamed intestine. Although several NP-based drugs have entered clinical trials for the treatment of IBD, most have failed due to premature drug release, weak targeting ability, and the high immune toxicity of some of the synthetic nanomaterials that have been used to fabricate the NPs. Therefore, there is still a need for rationally designed and stable NP drug delivery system that can specifically target drugs to the disease site, prolong the drug's residence time, and minimize systemic side effects. This review will analyze the current state of the art in NP-mediated drug delivery for IBD treatment. We will focus on topics such as deliverable targets (at the tissue or cellular level) for treating inflammation; the target-homing NP materials that can interact with such targets; and the major administration routes for treating IBD. These discussions will integrate notable trends in the research and development of IBD medications, including multi-responsive NP-mediated delivery and naturally-derived targeting NPs. Finally, current challenges and future directions will be presented in the hopes of advancing the study of NP-mediated strategies for treating IBD.
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http://dx.doi.org/10.2147/IJN.S210315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859086PMC
April 2020

Erythroid differentiation regulator-1 induced by microbiota in early life drives intestinal stem cell proliferation and regeneration.

Nat Commun 2020 01 24;11(1):513. Epub 2020 Jan 24.

Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, 100 Piedmont Ave, Atlanta, GA, 30303, USA.

Gut microbiota and their metabolites are instrumental in regulating intestinal homeostasis. However, early-life microbiota associated influences on intestinal development remain incompletely understood. Here we demonstrate that co-housing of germ-free (GF) mice with specific-pathogen free (SPF) mice at weaning (exGF) results in altered intestinal gene expression. Our results reveal that one highly differentially expressed gene, erythroid differentiation regulator-1 (Erdr1), is induced during development in SPF but not GF or exGF mice and localizes to Lgr5 stem cells and transit amplifying (TA) cells. Erdr1 functions to induce Wnt signaling in epithelial cells, increase Lgr5 stem cell expansion, and promote intestinal organoid growth. Additionally, Erdr1 accelerates scratch-wound closure in vitro, increases Lgr5 intestinal stem cell regeneration following radiation-induced injury in vivo, and enhances recovery from dextran sodium sulfate (DSS)-induced colonic damage. Collectively, our findings indicate that early-life microbiota controls Erdr1-mediated intestinal epithelial proliferation and regeneration in response to mucosal damage.
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http://dx.doi.org/10.1038/s41467-019-14258-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981263PMC
January 2020

Can naturally occurring nanoparticle-based targeted drug delivery effectively treat inflammatory bowel disease?

Expert Opin Drug Deliv 2020 01 28;17(1):1-4. Epub 2019 Nov 28.

Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Digestive Disease Research Group, Georgia State University, Atlanta, GA, USA.

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http://dx.doi.org/10.1080/17425247.2020.1698543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980994PMC
January 2020

Isolation, Purification, and Characterization of Ginger-derived Nanoparticles (GDNPs) from Ginger, Rhizome of .

Bio Protoc 2019 Oct;9(19)

Institute for Biomedical Science, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA.

Factors implicated in the pathophysiology of intestinal inflammation include defects in intestinal epithelial barrier function, abnormal immune responses, and activities of the gut microbiota. Current agents used to treat human Inflammatory Bowels Disease (IBD), chronic inflammation of digestive tract, have serious side effects. In addition, most of these treatments target the damaging factors while not providing pro-healing factors that repair the damaged intestine. Here we provide a method to isolate, purify and characterize a specific population from ginger (ginger-derived nanoparticles: GDNPs 2) with anti-inflammatory activities. GDNPs 2 as a drug vehicle are a novel natural, nontoxic delivery system, which target the inflamed intestinal mucosa, blocks damaging factors while promoting pro-healing factors and could easily be developed for large-scale production aimed at the treatment of IBD.
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http://dx.doi.org/10.21769/BioProtoc.3390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857645PMC
October 2019

Autologous Exosome Transfer: A New Personalised Treatment Concept to Prevent Colitis in a Murine Model.

J Crohns Colitis 2020 Jul;14(6):841-855

Digestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.

Background And Aims: Epigenetic information delivered by intestinal exosomes can be useful for diagnosing intestinal diseases, such as ulcerative colitis, but the therapeutic effects of intestinal exosomes have not been fully exploited. We herein developed an autologous exosome therapy that could treat intestinal disease without any risk of inducing a systemic immunological reaction.

Methods: Intestinal exosomes were isolated and purified from faeces by our newly developed multi-step sucrose gradient ultracentrifugation method. Lipopolysaccharide [LPS]-activated macrophages were employed to test the in vitro anti-inflammatory ability of intestinal exosomes. To evaluate the in vivo anti-inflammatory activity of our system, we gavaged dextran sulphate sodium [DSS]-induced colitic mice with their own healing phase intestinal exosomes.

Results: Mouse intestinal exosomes are round extracellular vesicles with a hydrodynamic diameter of ~140 [±20] nm and a surface charge of ~-12 [±3] mV. Among the exosomes obtained at four different stages of DSS-induced ulcerative colitis [1, before treatment; 2, DSS-treated; 3, healing phase; and 4, back to normal], the healing phase exosomes showed the best in vitro anti-inflammatory effects and promotion of wound healing. Moreover, oral co-administration of autologous healing phase exosomes with DSS was found to significantly reduce the risk of a second round of DSS-induced ulcerative colitis in mice.

Conclusions: Intestinal exosomes obtained during the healing phase that follows induced intestinal inflammation could strongly promote wound healing in the host. Oral administration of autologous exosomes from the healing phase could be a safe and effective approach for treating the ulcerative colitis of a given patient in the context of personalised medicine.
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http://dx.doi.org/10.1093/ecco-jcc/jjz184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346889PMC
July 2020

Silk fibroin-based nanotherapeutics: application in the treatment of colonic diseases.

Nanomedicine (Lond) 2019 09 10;14(17):2373-2378. Epub 2019 Jul 10.

Institute for Biomedical Sciences, Center for Diagnostics & Therapeutics, Georgia State University, Atlanta, GA 30302, USA.

The incidence of colonic diseases (e.g., inflammatory bowel diseases and colon cancer) is rapidly rising. Nanotherapeutic has been considered as a promising strategy in the treatment of colonic diseases. Silk fibroin (SF) has been widely used as a drug-carrier matrix. Interestingly, SF-based nanoparticles (SFNPs) have intrinsic anti-inflammatory activity, wound healing capacity and lysosomal environment-responsive drug-release property. With further investigations, the sequences of SF molecules could be precisely modified through chemical reactions or transgenic techniques to greatly improve the properties of SFNPs. Here, we review recent advances in the application of SFNPs toward the treatment of colonic diseases. We also discuss future developments that might improve the anti-inflammatory and anti-colon cancer activities of SF-based nanotherapeutics.
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http://dx.doi.org/10.2217/nnm-2019-0058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026768PMC
September 2019

Host-derived fecal microRNAs can indicate gut microbiota healthiness and ability to induce inflammation.

Theranostics 2019 9;9(15):4542-4557. Epub 2019 Jun 9.

Institute for Biomedical Sciences, Center for Inflammation, Immunity and Infection, Digestive Disease Research Group, Georgia State University, Atlanta, GA, USA.

Disruption of intestine-microbiota symbiosis can result in chronic gut inflammation. We hypothesize that assessing the initial inflammatory potential of the microbiota in patients is essential and that host-derived miRNAs, which can be found in feces, could fulfill this function. We investigated whether the gut microbiota composition impacts the fecal miRNA profile and thereby indicates its ability to influence intestinal inflammation. : We used high-throughput qPCR to compare fecal miRNA profile between germ-free and conventional mice. Conventionalization of germfree mice by various colitogenic and non-colitogenic microbiotas (IL10 and TLR5 associated microbiota) was performed. : We identified 12 fecal miRNAs impacted by the presence of a microbiota. Conventionalization of germfree mice by various colitogenic and non-colitogenic microbiotas associated with the development of intestinal inflammation (IL10 and TLR5 associated microbiota) yielded distinctively altered fecal miRNA profiles compared to that of mice receiving a "healthy" microbiota. Correlation analysis revealed the existence of interactions between the 12 abovementioned miRNAs and specific microbiota members. : These results showed that fecal miRNA profile can be differentially and specifically impacted by microbiota composition, and that miRNA could importantly serve as markers of the colitogenic potential of the microbiota. This is particularly relevant to assess individual state of the microbiota in patients with dysbiosis-related disorders, such as IBD and potentially determine their ability to respond to therapeutics.
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http://dx.doi.org/10.7150/thno.35282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599659PMC
August 2020

Oral Targeted Delivery by Nanoparticles Enhances Efficacy of an Hsp90 Inhibitor by Reducing Systemic Exposure in Murine Models of Colitis and Colitis-Associated Cancer.

J Crohns Colitis 2020 Jan;14(1):130-141

Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Center for Inflammation, Immunity and Infection, Digestive Disease Research Group, Georgia State University, Atlanta, GA, USA.

Background And Aims: Heat shock protein 90 [Hsp90]-targeted therapy has been proposed as a promising strategy for the treatment of ulcerative colitis [UC] and colitis-associated cancer [CAC]. Systemic administration of the Hsp90 inhibitor, 17-AAG, was found to be profoundly protective in preclinical mouse models of inflammatory bowel disease [IBD]. However, the therapeutic potential of 17-AAG is limited by potential side effects associated with its systemic exposure and the modest bioavailability afforded by its oral administration.

Methods: To address these issues, we used a versatile single-step surface-functionalizing technique to prepare a 17-AAG oral delivery system using PLGA/PLA-PEG-FA nanoparticles [NP-PEG-FA/17-AAG].

Results: NP-PEG-FA could be efficiently taken up by mouse Colon-26 cells and activated Raw 264.7 cells in vitro and by inflamed mouse colitis tissues in vivo. The therapeutic efficacy of orally administrated NP-PEG-FA/17-AAG was evaluated in in vivo models using dextran sulphate sodium [DSS]-induced UC and azoxymethane [AOM]/DSS-induced CAC, and the results indicated that NP-PEG-FA/17-AAG significantly alleviated the symptoms of UC and CAC. More importantly, our inflamed colitis-targeted 17-AAG nano-formulation reduced systemic exposure and provided a degree of therapeutic response similar to that obtained by systemic administration [intraperitoneal] of 17-AAG, but at a ten-fold lower dose.

Conclusions: We describe a convenient, orally administrated 17-AAG delivery system that exhibits enhanced efficacy in UC and CAC therapy while reducing systemic exposure. This system may represent a promising therapeutic approach for treating UC and CAC.
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http://dx.doi.org/10.1093/ecco-jcc/jjz113DOI Listing
January 2020

Early-Life Microbiota Exposure Restricts Myeloid-Derived Suppressor Cell-Driven Colonic Tumorigenesis.

Cancer Immunol Res 2019 04 19;7(4):544-551. Epub 2019 Feb 19.

Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia.

Gut microbiota and their metabolites are instrumental in regulating homeostasis at intestinal and extraintestinal sites. However, the complex effects of prenatal and early postnatal microbial exposure on adult health and disease outcomes remain incompletely understood. Here, we showed that mice raised under germ-free conditions until weaning and then transferred to specific pathogen-free (SPF) conditions harbored altered microbiota composition, augmented inflammatory cytokine and chemokine expression, and were hyper-susceptible to colitis-associated tumorigenesis later in adulthood. Increased number and size of colon tumors and intestinal epithelial cell proliferation in recolonized germ-free mice were associated with augmented intratumoral CXCL1, CXCL2, and CXCL5 expression and granulocytic myeloid-derived suppressor cell (G-MDSC) accumulation. Consistent with these findings, CXCR2 neutralization in recolonized germ-free mice completely reversed the exacerbated susceptibility to colitis-associated tumorigenesis. Collectively, our findings highlight a crucial role for early-life microbial exposure in establishing intestinal homeostasis that restrains colon cancer in adulthood.
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http://dx.doi.org/10.1158/2326-6066.CIR-18-0444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445671PMC
April 2019

Oral Gavage of Ginger Nanoparticle-Derived Lipid Vectors Carrying Dmt1 siRNA Blunts Iron Loading in Murine Hereditary Hemochromatosis.

Mol Ther 2019 03 12;27(3):493-506. Epub 2019 Jan 12.

Food Science & Human Nutrition Department, University of Florida, Gainesville, FL, USA. Electronic address:

Nanoparticles (NPs) have been utilized to deliver drugs to the intestinal epithelium in vivo. Moreover, NPs derived from edible plants are less toxic than synthetic NPs. Here, we utilized ginger NP-derived lipid vectors (GDLVs) in a proof-of-concept investigation to test the hypothesis that inhibiting expression of divalent metal-ion transporter 1 (Dmt1) would attenuate iron loading in a mouse model of hereditary hemochromatosis (HH). Initial experiments using duodenal epithelial organ cultures from intestine-specific Dmt1 knockout (KO) (Dmt1) mice in the Ussing chamber established that Dmt1 is the only active iron importer during iron-deficiency anemia. Further, when Dmt1 mice were crossed with mice lacking the iron-regulatory hormone, hepcidin (Hepc), iron loading was abolished. Hence, intestinal Dmt1 is required for the excessive iron absorption that typifies HH. Additional experiments established a protocol to produce GDLVs carrying functional Dmt1 small interfering RNAs (siRNAs) and to target these gene delivery vehicles to the duodenal epithelium in vivo (by incorporating folic acid [FA]). When FA-GDLVs carrying Dmt1 siRNA were administered to weanling Hepc mice for 16 days, intestinal Dmt1 mRNA expression was attenuated and tissue iron accumulation was blunted. Oral delivery of functional siRNAs by FA-GDLVs is a suitable therapeutic approach to mitigate iron loading in murine HH.
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http://dx.doi.org/10.1016/j.ymthe.2019.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401192PMC
March 2019

Overexpression of CD98 in intestinal epithelium dysregulates miRNAs and their targeted proteins along the ileal villus-crypt axis.

Sci Rep 2018 11 1;8(1):16220. Epub 2018 Nov 1.

Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Center for Inflammation, Immunity and Infection, Digestive Disease Research Group, Georgia State University, Atlanta, 30303, USA.

CD98 has been implicated in the experimental model of inflammatory bowel disease. We have previously shown that IEC-specific overexpression of CD98 mediates intestinal inflammation and intestinal epithelial barrier dysfunction. Mice overexpressing CD98 exhibited severe colitis and a greater susceptibility to CAC. Here we demonstrated CD98 overexpression to dysregulate homeostatic gradient profile of miRNA and protein expression along the ileal villus-crypt axis. Using miRNA-target gene prediction module, we observed differentially expressed miRNAs to target proteins of villus and crypt profoundly affected by CD98 overexpression. We have utilized online bioinformatics as methods to further scrutinize the biological meanings of miRNA-target data. We identified significant interactions among the differentially regulated proteins targeted by altered miRNAs in Tg mice. The biological processes affected by the predicted targets of miRNAs deviate from the homeostatic functions of the miRNA-gene-protein axis of the wildtype mice. Our results emphasize a dynamic perturbation of miRNA and protein expression in villus-crypt axis contributing to potential biological consequences of altering CD98 expression. Our findings also suggest the need for a consideration of arrays of interacting biological entities (i.e. miRNAs-mRNAs, protein-protein interaction) or a combination comparison for a better understanding of the disease pathology which is necessary for an effective therapeutic target development.
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http://dx.doi.org/10.1038/s41598-018-34474-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212412PMC
November 2018

TNFα gene silencing mediated by orally targeted nanoparticles combined with interleukin-22 for synergistic combination therapy of ulcerative colitis.

J Control Release 2018 10 11;287:235-246. Epub 2018 Aug 11.

Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Digestive Disease Research Group, Georgia State University, Atlanta, GA 30302, USA; Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA.

Pro-resolving factors that are critical for colonic epithelial restitution were down-regulated during the treatment with inhibitor of pro-inflammatory cytokines (e.g., anti-TNFα antibody) in ulcerative colitis (UC) therapy. We hypothesized that increased amounts of factors such as interleukin-22 (IL-22) during the therapeutic inhibition of TNFα could facilitate the resolution of intestinal inflammation. As combination therapy is an emerging strategy for UC treatment, we attempt to treat established UC based on the combination of TNFα siRNA (siTNF) and IL-22. Initially, we loaded siTNF into galactosylated polymeric nanoparticles (NPs). The resultant Gal-siTNF-NPs had a desirable average diameter (~261 nm), a narrow size distribution and a slightly negative surface charge (~-6 mV). These NPs successfully mediated the targeted delivery of siTNF to macrophages and efficiently inhibited the expression of TNFα. Meanwhile, IL-22 could obviously accelerate mucosal healing. More importantly, oral administration of Gal-siTNF-NPs plus IL-22 embedded in a hydrogel (chitosan/alginate) showed much stronger capacities to down-regulate the expression of pro-inflammatory factors and promote mucosal healing. This formulation also yielded a much better therapeutic efficacy against UC in a mouse model compared to hydrogel loaded with Gal-siTNF-NPs or IL-22 alone. Our results strongly demonstrate that Gal-siTNF-NP/IL-22-embedded hydrogel can target to inflamed colon, and co-deliver siTNF and IL-22 to boost the effects of either monotherapy, which may become a promising oral drug formulation and enable targeted combination therapy of UC.
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http://dx.doi.org/10.1016/j.jconrel.2018.08.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482469PMC
October 2018

Advances in Plant-derived Edible Nanoparticle-based lipid Nano-drug Delivery Systems as Therapeutic Nanomedicines.

J Mater Chem B 2018 Mar 29;6(9):1312-1321. Epub 2018 Jan 29.

Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30302 United States.

Plant-derived edible nanoparticles (PDNPs) are nano-sized membrane vesicles released by edible plants, such as grapefruit, ginger, broccoli, and lemon. They are non-toxic, have tissue-specific targeting properties, and can be mass-produced. Thus, they have great potential for clinical application. PDNPs offer multiple advantages over the currently available drug delivery systems, such as their relatively high internalization rate, low immunogenicity, proven stability in the gastrointestinal (GI) tract, and ability to overcome the blood-brain barrier but not cross the placental barrier. In this review, we will discuss these merits of PDNPs and analyze the current issues in PDNP research.
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http://dx.doi.org/10.1039/C7TB03207BDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053076PMC
March 2018