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In Vitro Models for Preclinical Drug Development
Published in Hyun Jung Kim, Biomimetic Microengineering, 2020
Jason Ekert, Sunish Mohanan, Julianna Deakyne, Philippa Pribul Allen, Nikki Marshall, Claire Jeong, Spiro Getsios
The most widely used animal models for IBD are the dextran sodium sulfate (DSS) and hapten reagent 2,4,6-trinitrobenzene sulfonic acid (TNBS) rodent models, and these models display numerous disadvantages. The damage to the epithelial barrier through chemical stimulation and the subsequent immune reaction it causes does not take into account the dysregulation of the innate or adaptive immune system in IBD (Wirtz and Neurath 2007). To account for the complexity in IBD etiology, researchers have taken transcriptomic, proteomic, metabolomic, and metagenomic approaches in an attempt to understand global disease networks and to identify genes, proteins, and metabolites that may be involved in disease pathogenesis. Although these approaches have provided valuable insights, they have fallen short of identifying potential high-value therapeutic targets in IBD.
Colon Targeted Drug Delivery Systems
Published in Ambikanandan Misra, Aliasgar Shahiwala, In-Vitro and In-Vivo Tools in Drug Delivery Research for Optimum Clinical Outcomes, 2018
For induction of colitis the most commonly used chemical agents used are trinitrobenzene sulfonic acid (TNBS), dextran sulphate sodium (DSS), or oxazolone. For evaluation of therapeutic efficiency of budesonide and budesonide nanoaprticles, all these three models were used in BALB/c mice. The purpose was to test the novel nanoformulation on both, acute and chronic colitis animal models, because the pathophysiological changes, such as clinical symptoms and immunological responses, may differ from model to model (Gottfries, Melgar, and Michaëlsson 2012). Also, it has been noted that the TNBS induced colitis has similar histologic features to Crohn’s disease, while, the DSS induced colitis resembles to ulcerative colitis (Alex et al. 2009). Therefore, such a comparative study was done to compare results from endoscopy, histology, and cytokine profiles from these different animal models. It was showed that nanoparticle delivery may improve the anti-inflammatory efficacy of budesonide in terms of endoscopical, histological, and biochemical parameters in comparison to the free drug. Moreover, such nanoparticle delivery via oral administration can be further improved by implementing pH-sensitive release characteristics, for example by using the appropriate coating (Ali et al. 2014).
Oral nanotechnological approaches for colon-specific drug delivery
Published in Ana Rute Neves, Salette Reis, Nanoparticles in Life Sciences and Biomedicine, 2018
Rute Nunes, Bruno Sarmento, Salette Reis, Pedro Fonte
Another strategy proposed by the same group was pH- and time-dependent (pH/time) polymeric NPs comprising Eudragit® FS 30D (poly(methyl acrylate-co-methyl methacrylate-comethacrylic acid, 7:3:1) as a pH-dependent polymer and Eudragit® RS100 (ammonio methacrylate copolymer, type B) as a time-dependent controlled release polymer [53]. pH-dependent and time-dependent NPs were also produced and compared with the pH/time NPs. The formulations displayed sizes around 250 nm, and different release patterns of BDS were obtained. Time-dependent NPs showed an independent pH drug release, suffering a premature, but sustained, drug release at pH 1.2 (stomach pH) and 6.5 (small intestine pH). On the contrary, both pH-dependent and pH-/time-dependent NPs avoided the initial burst drug release in acidic conditions. However, once at pH 7.4 (ileum and colon) pH-dependent NPs suffered a quick and almost complete release of the drug, while pH/time NPs showed a sustained drug release over 24 h. This behavior may explain the better in vivo distribution of pH-/time-dependent NPs in the GI tract of mice with DSS-induced colitis. The burst release observed for pH-dependent NPs at pH 7.4 may lead to systemic absorption at the ileum level with consequent unwanted side effects and lower drug concentrations at the affected tissues, reducing the therapeutic efficacy.
Serum and urine toxicometabolomics following gentamicin-induced nephrotoxicity in male Sprague-Dawley rats
Published in Journal of Toxicology and Environmental Health, Part A, 2018
Sung Ha Ryu, Ji Won Kim, Dahye Yoon, Suhkmann Kim, Kyu-Bong Kim
After thawing, urine samples at 4°C were centrifuged to remove solids. A 600-µl aliquot of the supernatant was added to a microcentrifuge tube containing 70 µl D2O solution with 5 mM DSS and 10 mM imidazole. DSS was used as the qualitative standard for the chemical shift scale. In addition, 30 µl 0.42% sodium azide was added. After vortexing, this solution was adjusted to pH 6.8, and the urine sample was analyzed with an NMR spectrometer. DSS was employed as the concentration reference at a concentration of 0.5 mM. Analytical conditions for urine samples are identical to serum analysis such as analytical instruments, NMR spectra acquisition parameters, and spectral binning. Identification and quantification of spectra were also determined by the same process as Chenomx NMR library. Metabolite concentrations were expressed as relative ratio values normalized to creatinine concentration, assuming a constant rate of creatinine excretion in all urine samples.
NMR and theoretical study on the linking properties of peroxovanadium(V) complexes with the 2-acylpyridine derivatives
Published in Journal of Coordination Chemistry, 2020
Zijuan Yi, Qi Deng, Xianyong Yu, Ruoxuan Chen, Xiaofang Li
All spectra were recorded on a Bruker AV-II 500 MHz NMR spectrometer. DSS (3-(trimethylsilyl)-propanesulfonic acid sodium salt) was used as an internal reference for 1H and 13C NMR chemical shifts. The 51V NMR chemical shift was measured relative to the external standard VOCl3 with upfield shifts considered negative. All pH measurements were measured by a Mettler Toledo Delta 320 pH-meter with a combinational glass calomel electrode.
Metabolomics approach to biomarkers of dry eye disease using 1H-NMR in rats
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Jung Dae Lee, Hyang Yeon Kim, Jin Ju Park, Soo Bean Oh, Hyeyoon Goo, Kyong Jin Cho, Suhkmann Kim, Kyu-Bong Kim
After the plasma samples were thawed at 4°C, a 350 μl aliquot was added to the microcentrifuge tube containing 350 μl deuterated water (D2O) solution with 4 mM trisodium phosphate (TSP) as the qualitative standard for the chemical shift scale. After thawing at 4°C, urine samples were centrifuged to remove solids. A 600 μl aliquot of supernatant was added to a microcentrifuge tube containing 70 μl D2O solution with 5 mM sodium trimethylsilylpropanesulfonate (DSS) and 100 mM imidazole. DSS was used as the qualitative standard for the chemical shift scale. Further, 30 μl 0.42% sodium azide was added. After vortexing, the plasma samples were analyzed with an NMR spectrometer within 48 hr. All spectra were determined using a Varian Unity Inova 600 MHz spectrometer at Pusan National University (Busan, Korea) operating at 26°C. 1H-NMR spectra were acquired using CPMG(Carr-Purcell-Meiboom-Gill) pulse to suppress water and macromolecule peaks. For urine sample, NMR spectra were measured using 16.2 μsec 90 pulse, and 3 sec relaxation delay, 3 sec acquisition time, and 13 min 9 sec total acquisition time. For plasma, 16.5 μsec 90 pulse, and 3 sec relaxation delay, 3 sec acquisition time, and 13 min 20 sec total acquisition time. Each sample was acquired with a total of 128 scans at a spectral width of 24,038.5 Hz. NMR spectra were reduced to data using the Chenomx NMR Suit program (ver. 8.3, Chenomx Inc., Edmonton, Alberta, Canada). The δ0.0 − 10 spectral region was segmented into regions of 0.04 ppm width providing 250 integrated regions in each NMR spectrum. This binning process endowed each segment with an integral value providing an intensity distribution of the whole spectrum with 250 variables prior to pattern recognition analysis. The spectrum region of water (δ4.5–5) was removed from the analysis to avoid differences in water suppression efficiency. The spectra were also identified and quantified using the Chenomx NMR Suit Professional software package ver. 8.3 (Chenomx Inc.). TSP and DSS were used as the concentration reference at a concentration of 2 and 0.5 mM, respectively.