scholarly journals Hyaluronic Acid in the Intestinal Tract: Influence of Structure, Rheology, and Mucoadhesion on the Intestinal Uptake in Rats

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1422
Author(s):  
Alexandro Barbosa de Souza ◽  
Marco Vinícius Chaud ◽  
Thais Francine Alves ◽  
Juliana Ferreira de Souza ◽  
Maria Helena Andrade Santana
Keyword(s):  
Hyaluronic Acid ◽  
Intestinal Tract ◽  
Molar Mass ◽  
Hydrodynamic Diameter ◽  
Average Molar Mass ◽  
Intestinal Membrane ◽  
Mixed Formulations ◽  
Jejunum Segment

Oral hyaluronic acid (HA) is a ubiquitous biopolymer that has gained attention as a treatment for local or systemic diseases. Here, we prepared and characterized structures of free HA (f-HA) with a high (>105 Da), intermediate (≤105 Da), and low (≤104 Da) average molar mass (MM); nanoparticles crosslinked with adipic dihydrazide (n-HA); and mixed formulations (mixed-HA) containing f-HA and n-HA. MM distribution determined the structure, hydrodynamic diameter, and zeta potential of the f-HAs. Crosslinking changed the physicochemical properties in n-HA. In vitro tack adhesion assays, using mucin tablets or a viable rat intestinal mucosa, showed better mucoadhesion with f-HA (intermediate MM) and mixed-HA (25% n-HA), especially in the jejunum segment. High MM f-HA presented negligible mucoadhesion. n-HA showed the deepest diffusion into the porous of the membranes. In vivo results showed that, except for high MM f-HA, there is an inverse relationship between rheological changes in the intestinal membrane macerates resulting from mucoadhesion and the effective intestinal permeability that led to blood clearance of the structures. We conclude that the n-HA formulations are promising for targeting other tissues, while formulations of f-HA (intermediate MM) and mixed-HA are better for treating dysbiosis.

scholarly journals Hyaluronic Acid-Poly(N-acryloyl glycinamide) Copolymers as Sources of Degradable Thermoresponsive Hydrogels for Therapy

Gels ◽  
2020 ◽  
Vol 6 (4) ◽  
pp. 42
Author(s):  
Mahfoud Boustta ◽  
Michel Vert
Keyword(s):  
Hyaluronic Acid ◽  
Molar Mass ◽  
Chemical Activation ◽  
Aqueous Media ◽  
Solution Temperature ◽  
One Pot ◽  
Feed Composition ◽  
Thermoresponsive Hydrogels

One-pot free-radical polymerization of N-acryloyl glycinamide in the presence of hyaluronic acid as transfer-termination agent led to new copolymers in high yields without any chemical activation of hyaluronic acid before. All the copolymers formed thermoresponsive hydrogels of the Upper Critical Solution Temperature-type in aqueous media. Gel properties and the temperature of the reversible gel ↔ sol transition depended on feed composition and copolymer concentration. Comparison with mixtures of hyaluronic acid-poly(N-acryloyl glycinamide) failed in showing the expected formation of graft copolymers conclusively because poly(N-acryloyl glycinamide) homopolymers are also thermoresponsive. Grafting and formation of comb-like copolymers were proved after degradation of inter-graft hyaluronic acid segments by hyaluronidase. Enzymatic degradation yielded poly(N-acryloyl glycinamide) with sugar residues end groups as shown by NMR. In agreement with the radical transfer mechanism, the molar mass of these released poly(N-acryloyl glycinamide) grafts depended on the feed composition. The higher the proportion of hyaluronic acid in the feed, the lower the molar mass of poly(N-acryloyl glycinamide) grafts was. Whether molar mass can be made low enough to allow kidney filtration remains to be proved in vivo. Last but not least, Prednisolone was used as model drug to show the ability of the new enzymatically degradable hydrogels to sustain progressive delivery for rather long periods of time in vitro.

scholarly journals Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Zhang ◽  
Guoyu Yin ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
Zhen Xie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Intracellular Degradation ◽  
Main Pathway ◽  
First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

scholarly journals In vitro and in vivo effect of hyaluronic acid modified, doxorubicin and gallic acid co-delivered lipid-polymeric hybrid nano-system for leukemia therapy

2019 ◽  
Vol Volume 13 ◽  
pp. 2043-2055 ◽  
Author(s):  
Yanping Shao ◽  
Wenda Luo ◽  
Qunyi Guo ◽  
Xiaohong Li ◽  
Qianqian Zhang ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Gallic Acid

scholarly journals Diacerein-Loaded Hyaluosomes as a Dual-Function Platform for Osteoarthritis Management via Intra-Articular Injection: In Vitro Characterization and In Vivo Assessment in a Rat Model

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 765
Author(s):  
Nouran O. Abdelmageed ◽  
Nadia M. Morsi ◽  
Rehab N. Shamma
Keyword(s):  
Hyaluronic Acid ◽  
Cartilage Damage ◽  
Entrapment Efficiency ◽  
Dual Function ◽  
In Vitro Characterization ◽  
Drug Entrapment Efficiency ◽  
Formulation Parameters ◽  
Acid Gel

The application of intra-articular injections in osteoarthritis management has gained great attention lately. In this work, novel intra-articular injectable hyaluronic acid gel-core vesicles (hyaluosomes) loaded with diacerein (DCN), a structural modifying osteoarthritis drug, were developed. A full factorial design was employed to study the effect of different formulation parameters on the drug entrapment efficiency, particle size, and zeta potential. Results showed that the prepared optimized DCN- loaded hyaluosomes were able to achieve high entrapment (90.7%) with a small size (310 nm). The morphology of the optimized hyaluosomes was further examined using TEM, and revealed spherical shaped vesicles with hyaluronic acid in the core. Furthermore, the ability of the prepared DCN-loaded hyaluosomes to improve the in vivo inflammatory condition, and deterioration of cartilage in rats (injected with antigen to induce arthritis) following intra-articular injection was assessed, and revealed superior function on preventing cartilage damage, and inflammation. The inflammatory activity assessed by measuring the rat’s plasma TNF-α and IL-1b levels, revealed significant elevation in the untreated group as compared to the treated groups. The obtained results show that the prepared DCN-loaded hyaluosomes would represent a step forward in the design of novel intra articular injection for management of osteoarthritis.

Results of an experimental study of hydrogel drainage containing ranibizumab in antiglaucoma operations

2021 ◽  
pp. 63-67
Author(s):  
I.I. Khusnitdinov ◽  
Keyword(s):  
Experimental Study ◽  
Hyaluronic Acid ◽  
Key Words ◽  
Experimental Research ◽  
Experimental Studies ◽  
Glaucoma Surgery ◽  
Control Group ◽  
Morphological Studies

Purpose. Еxperimental substantiation of the effectiveness of biocompatible biodegradable hydrogels based on hyaluronic acid and chitosan succinate as a carrier of ranibizumab in antiglaucoma operations. Material and methods. Hydrogel drainage (HD) was obtained immediately before surgery. A solution of ranibizumab (0.23 ml) was mixed with a solution of hyaluronic acid dialdehyde (0.5 ml), then a solution of chitosan succinate (0.5 ml) was added. Experimental studies were performed in 12 (12 eyes) healthy rabbits. The first group consisted of 6 eyes – 0.187 ml of ranibizumab per 1 ml of gel. In the control group, HD was used intraoperatively without the addition of ranibizumab (6 eyes). Morphological studies were performed on 7th, 21st, and 42nd days. Results. In experimental studies in vitro and in vivo, it was proved that ranibizumab, administered as a part of 0.1 ml of hydrogel drainage in the antiglaucoma surgery area is released within 3 weeks and suppresses vascularization, scarring of the operating area, and preserves the intrascleral cavity. The optimal concentration of ranibizumab was selected-0.02 ml in 0.1 ml of gel. Conclusion. The safety and effectiveness of the use of hydrogel drainage with ranibizumab based on hyaluronic acid dialdehyde and chitosan succinate in anti-glaucoma operations has been proven. Key words: experimental research, hydrogel drainage, ranibizumab, glaucoma surgery.

scholarly journals Andiroba Oil (Carapa guianensis Aublet) Nanoemulsions: Development and Assessment of Cytotoxicity, Genotoxicity, and Hematotoxicity

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Susana Suely Rodrigues Milhomem-Paixão ◽  
Maria Luiza Fascineli ◽  
Luis Alexandre Muehlmann ◽  
Karina Motta Melo ◽  
Hugo Leonardo Crisóstomo Salgado ◽  
...  
Keyword(s):  
Room Temperature ◽  
Future Application ◽  
Hydrodynamic Diameter ◽  
Therapeutic Application ◽  
Mtt Test ◽  
Carapa Guianensis ◽  
Toxicological Effects ◽  
Nih 3T3

Andiroba oil (AO) is obtained from an Amazonian plant and is used in traditional medicine. We carried out a comparative study to test the cytotoxicity, genotoxicity, and hematotoxicity of the oil and its nanoemulsion (AN) in vitro (fibroblasts, lineage NIH/3T3) and in vivo (Swiss mice). The AN was characterized by DLS/Zeta, and its stability was investigated for 120 days. The biological activity of AN was assessed in vitro by MTT test and cell morphology analyses and in vivo by micronucleus, comet, and hematotoxicity tests. The AN presented a hydrodynamic diameter (Hd) of 142.5±3.0 and PDI of 0.272±0.007 and good stability at room temperature. The MTT test evidenced the cytotoxicity of AO and of AN only at their highest concentrations, but AN showed lower cytotoxicity than AO. A lower cytotoxicity of AN, when compared to AO, is in fact an interesting data suggesting that during therapeutic application there will be a lower impact in the cell viability of healthy cells. Cytotoxicity, genotoxicity, and hematotoxicity were not observed in vivo. These tests on the biological and toxicological effects of andiroba oil and nanostructured oil are still initial ones but will give a direction to future application in cosmetics and/or the development of new phytotherapics.

Mitochondrial Targeted Doxorubicin-Triphenylphosphonium Delivered by Hyaluronic Acid Modified and pH Responsive Nanocarriers to Breast Tumor: in Vitro and in Vivo Studies

2018 ◽  
Vol 15 (3) ◽  
pp. 882-891 ◽  
Author(s):  
Hui-Na Liu ◽  
Ning-Ning Guo ◽  
Tian-Tian Wang ◽  
Wang-Wei Guo ◽  
Meng-Ting Lin ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Breast Tumor ◽  
In Vivo Studies ◽  
Ph Responsive

Fabrication, characterization and evaluation of the efficacy of gelatin/hyaluronic acid microporous scaffolds suffused with aloe-vera in a rat burn model

2021 ◽  
pp. 088532822110618
Author(s):  
Lalita Mehra ◽  
Smritee Mehra ◽  
Nidhi Tiwari ◽  
Thakuri Singh ◽  
Harish Rawat ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Growth Factor ◽  
Aloe Vera ◽  
Gamma Scintigraphy ◽  
Gravimetric Analysis ◽  
Burn Wounds ◽  
Partial Thickness ◽  
Partial Thickness Burn

Burn induced injuries are commonly encountered in civilian and military settings, leading to severe morbidity and mortality. Objective of this study was to construct microporous bioactive scaffolds of gelatin-hyaluronic acid suffused with aloe-vera gel (Gela/HA/AvG), and to evaluate their efficacy in healing partial-thickness burn wounds. Scaffolds were characterized using Fourier transform-infrared spectroscopy, Scanning electron microscopy, and Thermo-gravimetric analysis to understand intermolecular interactions and morphological characteristics. In-vitro fluid uptake ability and hemolytic index of test scaffolds were also determined. In-vitro collagenase digestion was done to assess biodegradability of scaffolds. Wound retraction studies were carried out in Sprague Dawley rats inflicted with partial-thickness burn wounds to assess and compare efficacy of optimized scaffolds with respect to negative and positive control groups. In-vivo gamma scintigraphy using Technetium-99m labeled Immunoglobulin-G ( 99m Tc-IgG) as imaging agent was also performed to validate efficacy results. Histological and immunohistochemical comparison between groups was also made. Scaffolds exhibited mircoporous structure, with pore size getting reduced from 41.3 ± 4.3 µm to 30.49 ± 5.7 µm when gelatin conc. was varied from 1% to 5%. Optimized test scaffolds showed sustained in-vitro swelling behavior, were biodegradable and showed hemolytic index in range of 2.4–4.3%. Wound retraction study along with in-vivo gamma scintigraphy indicated that Gela/HA/AvG scaffolds were not only able to reduce local inflammation faster but also accelerated dermis regeneration. Immunohistochemical analysis, in terms of expression levels of epidermal growth factor and fibroblast growth factor-2 also corroborated in-vivo efficacy findings. Gela/HA/AvG scaffolds, therefore, can potentially be developed into an effective dermal regeneration template for partial-thickness burn wounds.

CD44-dependent lymphoma cell dissemination: a cell surface CD44 variant, rather than standard CD44, supports in vitro lymphoma cell rolling on hyaluronic acid substrate and its in vivo accumulation in the peripheral lymph nodes

2001 ◽  
Vol 114 (19) ◽  
pp. 3463-3477
Author(s):  
Shulamit B. Wallach-Dayan ◽  
Valentin Grabovsky ◽  
Jürgen Moll ◽  
Jonathan Sleeman ◽  
Peter Herrlich ◽  
...  
Keyword(s):  
Cell Migration ◽  
Hyaluronic Acid ◽  
Lymph Node ◽  
Cell Surface ◽  
Lymph Nodes ◽  
Local Tumor ◽  
Cd44 Variant ◽  
Peripheral Lymph

Cell motility is an essential element of tumor dissemination, allowing organ infiltration by cancer cells. Using mouse LB lymphoma cells transfected with standard CD44 (CD44s) cDNA (LB-TRs cells) or with the alternatively spliced CD44 variant CD44v4-v10 (CD44v) cDNA (LB-TRv cells), we explored their CD44-dependent cell migration. LB-TRv cells, but not LB-TRs or parental LB cells, bound soluble hyaluronic acid (HA) and other glycosaminoglycans (GAGs), and exclusively formed, under physiological shear force, rolling attachments on HA substrate. Furthermore, LB-TRv cells, but not LB-TRs cells or their parental LB cells, displayed accelerated local tumor formation and enhanced accumulation in the peripheral lymph nodes after s.c. inoculation. The aggressive metastatic behavior of i.v.-injected LB-TRV cells, when compared with that of other LB-transfectants, is attributed to more efficient migration to the lymph nodes, rather than to local growth in the lymph node. Injection of anti-CD44 monoclonal antibody or of the enzyme hyaluronidase also prevented tumor growth in lymph nodes of BALB/c mice inoculated with LB-TRv cells. The enhanced in vitro rolling and enhanced in vivo local tumor growth and lymph node invasion disappeared in LB cells transfected with CD44v cDNA bearing a point mutation at the HA binding site, located at the distal end of the molecule constant region. These findings show that the interaction of cell surface CD44v with HA promotes cell migration both in vitro and in vivo, and they contribute to our understanding of the mechanism of cell trafficking, including tumor spread.

Interfering With Hyaluronic Acid Metabolism Suppresses Glioma Cell Proliferation by Regulating Autophagy

2020 ◽  
Author(s):  
Tao Yan ◽  
Xin Chen ◽  
Hua Zhan ◽  
Penglei Yao ◽  
Ning Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Hyaluronic Acid ◽  
Tumor Microenvironment ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Glioma Cell ◽  
Glioma Cells

Abstract BackgroundThe tumor microenvironment plays an important role in tumor progression. Hyaluronic acid (HA), an important component of the extracellular matrix in the tumor microenvironment, abnormally accumulates in a variety of tumors. Whereas the role of abnormal HA metabolism in glioma remains unclear. MethodsThe expression level of hyaluronic acid (HA) was analyzed by ELISA assay and proteins such as HAS3, CD44, P62, LC3, CCND1 and CCNB1 were measured with Western blot analysis. The cell viability and proliferation were measured by MTT and KI67 immunofluorescence staining respectively. Autophagic vesicles and autophagosomes were quantified by transmission electron microscopy (TEM) and GFP-RFP-LC3 fluorescence analysis respectively. Cell cycle was analyzed by flowcytometry and Western blot analysis. Immunohistochemical (IHC) staining was used to detect expression levels of HA, Ki67, HAS3 and CD44 in human and mouse tumor tissues. Lentivirus constructed HAS3 and CD44 knockout stable glioma cells were transplanted to BALB/C nude mice for in vivo experiments. 4-Methylumbelliferone (4MU) was also used to treat glioma bearing mice for verifing its anti-tumor ability. The expression curve of HAS3, CD44 and the disease-free survival (DFS) curves for HAS3, CD44 in patients with LGG and GBM was performed based on TCGA database. ResultsAs shown in the present study, HA, hyaluronic acid synthase 3 (HAS3) and a receptor of HA named CD44 are expressed at high levels in human glioma tissues and negatively correlated with the prognosis of patients with glioma. Silencing HAS3 or blocking CD44 inhibited the proliferation of glioma cells in vitro and in vivo. The underlying mechanism was attributed to the inhibition of autophagy flux and further maintaining glioma cell cycle arrest in G1 phase. More importantly, 4-Methylumbelliferone (4-MU), a small competitive inhibitor of UDP with the ability to penetrate the blood-brain barrier (BBB), also inhibited the proliferation of glioma cells in vitro and in vivo. ConclusionApproaches that interfere with HA metabolism by altering the expression of HAS3 and CD44 and the administration of 4-MU potentially represent effective strategies for glioma treatment.

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