scholarly journals Elucidation of the time-dependent degradation process in insoluble hyaluronic acid formulations with a controlled degradation rate

2019 ◽  
Vol 10 ◽  
pp. 204173141988503 ◽  
Author(s):  
Akiko Uemura ◽  
Shingo Ogawa ◽  
Yasuyuki Isono ◽  
Ryou Tanaka
Keyword(s):  
Hyaluronic Acid ◽  
Degradation Rate ◽  
Morphological Changes ◽  
Sodium Hyaluronate ◽  
Degradation Process ◽  
Pharmaceutical Products ◽  
The Body ◽  
Time Dependent ◽  
Swelling Ratio

Degradation rate of hyaluronic acid to prolong its stability in vivo would be beneficial. We investigated a potential solution for prolonging the stability of hyaluronic acid within the body. We focused on decreasing the swelling ratio to slow the degradation rate of hyaluronic acid by insolubilizing sodium hyaluronate without using potentially harmful substances such as crosslinkers or modifiers. Hyaluronic acid formulations were created with three different swelling ratios and time-dependent morphological changes in hyaluronic acid formulations and were scored based on each swelling ratio. In vivo degradation was modeled in simulated body fluid and the extent of decay of test membranes were monitored over time. Results showed that, by adjusting the swelling ratio, the degradation rate of hyaluronic acid formulation could be controlled. Our research could lead to improvements in many products, not only preventive materials for postoperative adhesions, but also pharmaceutical products such as osteoarthritis treatments and cosmetic medicines.

scholarly journals Intrathoracic retention of insoluble hyaluronic acid and its absorption process in rats

2019 ◽  
Vol 43 (4) ◽  
pp. 283-287
Author(s):  
Akiko Uemura ◽  
Shingo Ogawa ◽  
Ryou Tanaka
Keyword(s):  
Hyaluronic Acid ◽  
Wistar Rats ◽  
Morphological Changes ◽  
Degradation Process ◽  
Time Dependent ◽  
Thoracic Cavity ◽  
Absorption Process ◽  
Close Relationship ◽  
In Vivo Degradation

Background: Post-thoracotomy adhesions are frequent postoperative complications. It has been reported that insoluble hyaluronic acid may prevent adhesions. Materials and methods: This study had two objectives: first, to determine the in vivo degradation and absorption process, as well as the intrathoracic retention, of solid insoluble hyaluronic acid membrane; and second, to elucidate the association between postoperative intrathoracic retention and the morphological changes of insoluble hyaluronic acid in 12 Wistar rats. Insoluble hyaluronic acid membranes were cut into 2.0 cm × 1.0 cm rectangles in a dry state. After weighing, the test membranes were soaked and washed with saline to be implanted after pericardiotomy via thoracotomy. At Days 4, 7, 10, 14, and 28 after implantation, the rats were euthanized, the chest was opened, and the condition and implantation site of the inserted test membrane were examined. Results: Although approximately 10 days were required for the test membrane to decrease to half in the thoracic cavity, the intrathoracic remnant decreased to a mean of ~2% just 4 days later. Conclusion: This study clarified the time-dependent degradation process and remnants of insoluble hyaluronic acid in the thoracic cavity. A close relationship between the intrathoracic remnant of insoluble hyaluronic acid and its morphological change associated with degradation was demonstrated.

scholarly journals Click Activated Protodrugs Against Cancer Increase the Therapeutic Potential of Chemotherapy through Local Capture and Activation

2020 ◽  
Author(s):  
Kui Wu ◽  
Nathan Yee ◽  
Sangeetha Srinivasan ◽  
Amir Mahmoodi ◽  
Michael Zakharian ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Unmet Need ◽  
Sodium Hyaluronate ◽  
Maximum Tolerated Dose ◽  
The Body ◽  
In Vivo Studies ◽  
Tumor Biomarker ◽  
Tumor Site

<div> <div> <div> <p>A desired goal of targeted cancer treatments is to achieve high tumor specificity with minimal side effects. Despite recent advances, this remains difficult to achieve in practice as most approaches rely on biomarkers or physiological differences between malignant and healthy tissue, and thus benefit only a subset of patients in need of treatment. To address this unmet need, we introduced a Click Activated Protodrugs Against Cancer (CAPAC) platform that enables targeted activation of drugs at a specific site in the body, i.e., a tumor. In contrast to antibodies (mAbs, ADCs) and other targeted approaches, the mechanism of action is based on in vivo click chemistry, and is thus independent of tumor biomarker expression or factors such as enzymatic activity, pH, or oxygen levels. The platform consists of a tetrazine-modified sodium hyaluronate-based biopolymer injected at a tumor site, followed by one or more doses of a trans-cyclooctene (TCO)- modified cytotoxic protodrug with attenuated activity administered systemically. The protodrug is captured locally by the biopolymer through an inverse electron-demand Diels-Alder reaction between tetrazine and TCO, followed by conversion to the active drug directly at the tumor site, thereby overcoming the systemic limitations of conventional chemotherapy or the need for specific biomarkers of traditional targeted therapy. Here, TCO-modified protodrugs of four prominent cytotoxics (doxorubicin, paclitaxel, etoposide and gemcitabine) are used, highlighting the modularity of the CAPAC platform. In vitro evaluation of cytotoxicity, solubility, stability and activation rendered the protodrug of doxorubicin, SQP33, as the most promising candidate for in vivo studies. Studies in rodents show that a single injection of the tetrazine-modified biopolymer, SQL70, efficiently captures SQP33 protodrug doses given at 10.8-times the maximum tolerated dose of conventional doxorubicin with greatly reduced systemic toxicity. </p> </div> </div> </div>

RATE OF THYROXINE SECRETION BY MALE AND LAYING JAPANESE QUAIL: IDENTIFICATION OF THE RADIOACTIVE THYROXINE DEGRADATION COMPONENT OF THE MULTIPHASIC 131I CURVE

1975 ◽  
Vol 65 (1) ◽  
pp. 65-71 ◽  
Author(s):  
G. A. ROBINSON ◽  
K. H. TAM
Keyword(s):  
Japanese Quail ◽  
Degradation Rate ◽  
The Body ◽  
Secretion Rate ◽  
Distribution Space ◽  
Rapid Loss ◽  
Serum Samples ◽  
Time Period

SUMMARY Counting of radioactivity in Japanese quail in vivo showed a rapid loss of 131I from the body 12–24 h after the i.v. injection of [131I]thyroxine (T4), followed by a period of slow decrease in counting rates to 96 h. From comparison of these [131I]T4 curves with curves for 131iodide-injected birds and from counts on serum and other tissues in vitro it was concluded that, for Japanese quail, the T4 secretion rate should be calculated using serum samples taken during the first 12 h. Using this time period, the parameters measured were: T4 distribution space, laying hens 45·7 and mature cocks 26·3 ml/100 g body weight; fractional degradation rate for T4, hens 5·73 and cocks 3·12/day; serum T4 concentration (Tetrasorb125 method), hens 1·20 ± 0.07 and cocks 1·34 ± 0.05 (s.e.m.)μg/100 ml (n= 16); T4 secretion rate, hens 3·14 and cocks 1·10 μg/100 g/day.

In vivo multi-photon luminescence imaging of cerebral vasculature and blood–brain barrier integrity using gold nanoparticles

2015 ◽  
Vol 3 (15) ◽  
pp. 2935-2938 ◽  
Author(s):  
Hwan-Jun Yoon ◽  
Eek-Sung Lee ◽  
Minseok Kang ◽  
Yong Jeong ◽  
Ji-Ho Park
Keyword(s):  
Gold Nanoparticles ◽  
Spatial Resolution ◽  
High Spatial Resolution ◽  
Morphological Changes ◽  
Time Dependent ◽  
Cerebral Vasculature ◽  
Barrier Integrity ◽  
Cerebral Microvasculature ◽  
Blood Brain Barrier Integrity

Time-dependent morphological changes of cerebral microvasculature can be visualized with high spatial resolution using the multi-photon luminescence of gold nanoparticles.

Time-dependent biodistribution, clearance and biocompatibility of magnetic fibrin nanoparticles: an in vivo study

Nanoscale ◽  
2015 ◽  
Vol 7 (21) ◽  
pp. 9676-9685 ◽  
Author(s):  
Periyathambi Prabu ◽  
Weslen S. Vedakumari ◽  
Thotapalli P. Sastry
Keyword(s):  
Biomedical Research ◽  
The Body ◽  
Time Dependent ◽  
In Vivo Study

Recently, bioretention and toxicity of injected nanoparticles in the body has drawn much attention in biomedical research.

Bioinspired Drug Delivery Carrier for Enhanced Tumor-Targeting in Melanoma Mice Model

2019 ◽  
Vol 15 (7) ◽  
pp. 1482-1491 ◽  
Author(s):  
Xu Wang ◽  
Gao-Feng Liang ◽  
Xue-Qin Hao ◽  
Shu-Ying Feng ◽  
Lu Dai ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Near Infrared ◽  
Imaging System ◽  
Morphological Changes ◽  
The Body ◽  
Control Group ◽  
Mice Model ◽  
Normal Tissues ◽  
Specific Distribution

As a widely used first-line chemotherapy drug for tumor, Doxorubicin (DOX) can induce various side effects on normal tissues because of its non-specific distribution in the body. Emerging evidence has shown that platelets have the capability to recognize and interact with tumor cells. Inspired by this, the platelet-based drug delivery system was constructed by loading of DOX in platelet cytoplasm and modification of transferrin on the surface of platelet (Tf-P-DOX). The encapsulation efficiency of DOX in platelet was the highest at the DOX concentration of 0.05 mM, and reached to 64.9%. Fluorescence microscopy showed that the Tf-P-DOX facilitated cell uptakes and enhanced intracellular drug accumulation in B16F10 cells. Compared with free DOX, Tf-P-DOX exhibited an enhanced effect on cell apoptosis at the same concentration of DOX. In vivo imaging system showed that the near-infrared fluorescence of B16F10 tumor-bearing mice was mainly accumulated in the tumor site, which caused the inhibition of tumor growth in mice. The morphological changes of tumor tissue in Tf-P-DOX group was significant in comparison with those of the control group, including the small nucleus, the insufficiency of cancerous nest, and the infiltration of inflammatory cells, while Tf-P-DOX did not show significant adverse effects on normal tissues. Compared with the control group, the levels of caspase 9 and caspase 3 protein expressions were increased significantly in Tf-P-DOX group. Our studies suggest platelets can be repurposed as promising carriers for efficient targeting and treatment of solid tumors.

Abstract 241: In Vivo Response to Dynamic Hyaluronic Acid Hydrogels

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Jennifer L Young ◽  
Jeremy Tuler ◽  
Rebecca Braden ◽  
Pamela Schup-Magoffin ◽  
Jacquelyn Schaefer ◽  
...  
Keyword(s):  
Immune Response ◽  
Hyaluronic Acid ◽  
Critical Role ◽  
Host Cells ◽  
Time Dependent ◽  
Post Injection ◽  
High Concentration ◽  
Glycol Diacrylate

Tissue-specific elasticity arises in part from developmental changes in extracellular matrix over time, e.g. ~ 10-fold myocardial stiffening in the chicken embryo. When this time-dependent stiffening is mimicked in vitro with a thiolated hyaluronic acid (HA-SH)/poly(ethylene glycol) diacrylate (PEGDA) hydrogel, improved cardiomyocyte maturation has been observed. However, host interactions, matrix polymerization, and stiffening kinetics remain uncertain in vivo, and each plays a critical role in therapeutic applications using HA-SH. In order to assess in vivo feasibility and biocompatibility of HA-SH/PEGDA hydrogels, subcutaneous injections were first performed. Hematological and histological analysis of subcutaneously injected HA-SH/PEGDA hydrogels showed minimal systemic immune response and host cell infiltration. Most importantly, subcutaneously injected HA-SH/PEGDA hydrogels exhibited time dependent porosity and stiffness changes at a rate similar to hydrogels polymerized in vitro, as measured by atomic force microscopy. When injected intramyocardially, host cells begin to actively degrade HA-SH/PEGDA hydrogels within 1-week post-injection, continuing this process while producing matrix to nearly replace the hydrogel within 1 month post-injection. While non-thiolated HA did not degrade after injection into the myocardium, it also did not elicit an immune response, unlike HA-SH/PEGDA, HA-SH/low concentration PEGDA, or high concentration HA-SH only hydrogels, where visible granulomas and macrophage infiltration were present at 1 month post-injection, as indicated by CD45 (lymphocyte marker) and CD68 (macrophage marker) staining, likely due to reactive thiol groups. Altogether, these data suggest that the HA-SH/PEGDA hydrogel responds appropriately in a less vascularized niche and stiffens as had been demonstrated in vitro, but in more vascularized tissues, in vivo applicability appears limited.

scholarly journals Immunohistochemical analysis of the inflammatory reaction within the implantation bed of a collagen hemostatic biomaterial

2021 ◽  
Author(s):  
◽  
Carlos Arturo Herrera Vizcaino
Keyword(s):  
Wound Healing ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Degradation Rate ◽  
Ex Vivo ◽  
The Body ◽  
Cellular Reaction ◽  
Intergroup Comparison ◽  
Pro Inflammatory Cytokines

Current research on medical biomaterials have shown that the physical and chemical characteristics of biomaterials determine the body inflammatory cellular reaction after their implantation. The aim of this study was to evaluate the individual effects of the physical characteristics over the initial biomaterial-cellular interaction and the inflammatory cellular reaction. For this purpose, an equine-derived collagen hemostatic sponge (E-CHS) was modified by pressing and evaluated using ex vivo, in vitro and in vivo methods. The E-CHS was pressed by applying constant pressure (6.47± 0.85 N) for 2 min using a sterile stainless-steel cylinder and cut in segments of 1cm2. Subsequently, E-CHS and the pressed equine-derived collagen hemostatic sponge (P-E-CHS) were studied as two independent biomaterials and compared to a control group (CG). A blood concentrate containing inflammatory cells known as platelet rich fibrin (PRF) was used to mimic the initial biomaterial-cell interaction and to measure the absorption coefficient of the biomaterials to liquid PRF (iPAC). Additionally, the biomaterials were cultivated together with PRF for 3 and 6 days to measure the induction of pro-inflammatory cytokines (TNF-α and IL-8). The results were obtained through enzyme-linked immunosorbent assay (ELISA) and histological methods. PRF cultivated without biomaterials served as the CG. Additionally, the biomaterials were evaluated in vivo using a subcutaneous model in Wistar rats and compared to sham operated animals (CG) representing physiologic wound healing. After 3, 15 and 30 days, the explanted samples were evaluated using histochemical and immunohistochemical (IHC) staining using the following markers: CD68 (pan macrophages), CCR7 (pro-inflammatory macrophages, M1), CD206 (pro-wound healing macrophages, M2) and α-Smooth Muscle Actin (α-SMA; vessel identification). After the mixture of liquid PRF with both biomaterials for 15 minutes, the ex vivo results showed that E-CHS was penetrated by cells, whereas P-E-CHS was cell-occlusive. Additionally, P-E-CHS induced a higher release of pro-inflammatory cytokines compared to liquid PRF alone (CG) and E-CHS after 3 days (P< 0.05). Although the biomaterial was pressed, the difference of the iPAC value did not show statistical differences. In vivo, the CG induced at day 3 a higher inflammatory response compared to the experimental groups (EG) (P< 0.05). The intergroup comparison showed that P-E-CHS induced a higher presence of macrophages (CD68+/CC7+) compared to E-CHS at day 3 (P< 0.05). Only CD68+/CCR7+ mononuclear cells (MNCs) were observed without multinucleated giant cells (MNGCs). After 15 days, the presence of macrophages (CD68+ P<0.01 /CCR7+ P<0.001 /CD206+ P<0.05) reduced considerably in the CG. On the contrary, the inflammatory response increased in the EGs (CD68+/CCR7+). The intergroup comparison showed that this increment was statistically significant when comparing E-CHS and P-E-CHS to the CG at day 15 (P<0.01 and P< 0.05 respectively). At this time point, a reduced number of MNGCs were observed in the EGs. In the CG no MNGCs were observed. Furthermore, E-CHS showed a faster degradation rate and was fully invaded by cells and vessels formed in its interior region. On the other hand, P-E-CHS remained occlusive to cell penetration and vessels were formed only in the periphery. After 30 days, the cellular reaction shifted to a higher number of M2 macrophages (CD260+) in all groups and a reduced presence of CD68+ and CCR7+ MNCs. Both biomaterials degraded and only small fragments were found in the implantation bed surrounded by MNGCs (CCR7+). These results are of high clinical relevance and show that changes in biomaterial properties have a significant impact on their interaction with the body. They also serve as insight into the possibility to develop versatile biomaterials with different applications. For example, E-CHs can be applied to support hemostasis in a bleeding alveolar socket and P-E-CHs by being cell occlusive and having a delayed degradation rate can be applied for guided bone and tissue regeneration.

scholarly journals Click Activated Protodrugs Against Cancer Increase the Therapeutic Potential of Chemotherapy through Local Capture and Activation

2020 ◽  
Author(s):  
Kui Wu ◽  
Nathan Yee ◽  
Sangeetha Srinivasan ◽  
Amir Mahmoodi ◽  
Michael Zakharian ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Unmet Need ◽  
Sodium Hyaluronate ◽  
Maximum Tolerated Dose ◽  
The Body ◽  
In Vivo Studies ◽  
Tumor Biomarker ◽  
Tumor Site

<div> <div> <div> <p>A desired goal of targeted cancer treatments is to achieve high tumor specificity with minimal side effects. Despite recent advances, this remains difficult to achieve in practice as most approaches rely on biomarkers or physiological differences between malignant and healthy tissue, and thus benefit only a subset of patients in need of treatment. To address this unmet need, we introduced a Click Activated Protodrugs Against Cancer (CAPAC) platform that enables targeted activation of drugs at a specific site in the body, i.e., a tumor. In contrast to antibodies (mAbs, ADCs) and other targeted approaches, the mechanism of action is based on in vivo click chemistry, and is thus independent of tumor biomarker expression or factors such as enzymatic activity, pH, or oxygen levels. The platform consists of a tetrazine-modified sodium hyaluronate-based biopolymer injected at a tumor site, followed by one or more doses of a trans-cyclooctene (TCO)- modified cytotoxic protodrug with attenuated activity administered systemically. The protodrug is captured locally by the biopolymer through an inverse electron-demand Diels-Alder reaction between tetrazine and TCO, followed by conversion to the active drug directly at the tumor site, thereby overcoming the systemic limitations of conventional chemotherapy or the need for specific biomarkers of traditional targeted therapy. Here, TCO-modified protodrugs of four prominent cytotoxics (doxorubicin, paclitaxel, etoposide and gemcitabine) are used, highlighting the modularity of the CAPAC platform. In vitro evaluation of cytotoxicity, solubility, stability and activation rendered the protodrug of doxorubicin, SQP33, as the most promising candidate for in vivo studies. Studies in rodents show that a single injection of the tetrazine-modified biopolymer, SQL70, efficiently captures SQP33 protodrug doses given at 10.8-times the maximum tolerated dose of conventional doxorubicin with greatly reduced systemic toxicity. </p> </div> </div> </div>

Innovation of hyaluronic acid-protamine microparticles and their kinetics in vivo

2016 ◽  
Vol 26 (01n02) ◽  
pp. 45-51 ◽  
Author(s):  
S. Harada ◽  
S. Ehara ◽  
T. Segawa ◽  
K. Ishii ◽  
T. Sato ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Anticancer Drug ◽  
The Body ◽  
The Mean ◽  
Kinetics Of ◽  
Pixe Method ◽  
Kinetics In Vivo ◽  
Number Of Particles

The nanoparticles, which releases anticancer drug with response to radiation, were developed. Also, two categories were tested: (i) their ability to release anticancer drug in vitro; and (ii) their kinetics in the body, when they were injected through tail vein of BALB/c mice in vivo. To prepare the particles, hyaluronic acid and protamine were mixed into carboplatin solution, and reacted for 30 min in room temperature. Those particles were exposed to a single dose of 10 Gy of 140 KeV X-ray. Their ability to release carboplatin with response to radiation was expressed as the percentage of ruptured particles, basing on images of particles, using micro PIXE camera. The amount of released carboplatin was measured by quantitative PIXE method. The kinetics of particles in body was assessed by counting the number of particles, which were trapped in lungs, using micro PIXE camera. The mean diameter of particles was 743 ± 34 nm. By irradiation, 59.3 ± 7.23% of particles ruptured, and 95.9 ± 2.3% carboplatin was released from particles. The trapped particles in lungs were significantly reduced, when compared with previous alginate-hyaluronic particles.

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