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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
During the last few years the use of intestinal cell lines has been increased to study the intestinal permeability and for toxicity evaluations. The human epithelial cell line Caco-2 has been widely used as a model of the intestinal epithelial barrier. Caco-2 (Cancer coli-2) was established from a human colorectal adenocarcinoma by Jorgen Fogh at the Sloan-Kettering Cancer Research Institute. Caco-2 cells develop morphologic characteristics of normal enterocytes when grown on plastic dishes or nitrocellulose filters. The monolayers of Caco-2 mimic intestinal absorptive epithelium and represent a very useful tool for studying transepithelial transport. Another cell line of interest is the human colon adenocarcinoma cell line HT29. It is receiving special interest in studies focused on bioavailability, due to the ability to express characteristics of mature intestinal cells (Lea 2015).
Methods and Protocols for In Vitro Animal Nanotoxicity Evaluation: A Detailed Review
Published in Vineet Kumar, Nandita Dasgupta, Shivendu Ranjan, Nanotoxicology, 2018
Venkatraman Manickam, Leema George, Amiti Tanny, Rajeeva Lochana, Ranjith Kumar Velusamy, M. Mathan Kumar, Bhavapriya Rajendran, Ramasamy Tamizhselvi
The human undifferentiated colon adenocarcinoma cell line, Caco-2, is commonly used while evaluating the uptake during ingestion of various engineered nanomaterials. Some of the nanomaterials tested using this cell line include metal oxide, polymeric, and carbon based nanoparticles. Occasionally, primary cells like dendritic cells derived from murine intestines were used to study the toxicities of silicon dioxide and titanium dioxide nanoparticles (Winter et al. 2011; Love et al. 2012). When proposed nanotherapy is intended for cancer treatment, transformed cells of the cancerous organ/tissue of origin are the usual choice. Thus immortal cancer cells like HeLa, MCF-7, HCT-116, and BEAS-2B are preferred. As the control in these cases, noncancerous 3T3 fibroblast cells are used. In the case of topical transdermal applications, keratinocytes and dermal fibroblast cells are commonly used. For instance, the human-derived keratinocyte HaCaT cell line is used for studying the toxicity arising from TiO2 and ZnO nanoparticles. Similarly, immortalized adult human epidermal keratinocytes (HEKa) are applied while checking for ZnO nanoparticles based cytotoxic effects or induced DNA damage (Sharma et al. 2011) and cell inflammatory responses upon exposure to high-aspect ratio QDs (Zhang et al. 2008). A mouse keratinocyte cell line (HEL-30), was used while looking for size and crystallinity derived cytotoxicity in TiO2 nanoparticles (Braydich-Stolle et al. 2009).
Contribution of Bioavailable Silicon in Human Health
Published in Debasis Bagchi, Manashi Bagchi, Metal Toxicology Handbook, 2020
Caco-2 cells are a well-accepted in vitro model of the human intestinal epithelium to investigate the transport across the intestinal barrier in both the absorption and excretion directions. In this model, amorphous silica particles with diameters of 50, 100, and 200 nm were incubated in simulated fasted-state and fed-state gastric and intestinal fluids. In the fed-state, silica particles agglomerated with the increased particle size inhibiting the particles’ absorption into Caco-2 cells and particles’ transport through the cells. There was no cytotoxicity when the average particle size was >100 nm, independent of the fluid and the concentration.198 In a separate study, silicon supplied as OSA stabilized by vanillin complex (OSA-VC) was incubated with Caco-2 cells. OSA-VC transport was concentration-dependent and increased with duration of incubation. Absorption and excretion rates were similar indicating paracellular diffusion. Cellular accumulation of Si, polarized from the apical side of cells, was furthermore detected suggesting silicon ingested as a food supplement as OSA-VC, crosses the intestinal mucosa by passive diffusion, viz., paracellular pathway through intercellular tight junctions and accumulates by facilitated diffusion.199 The cytotoxicity and genotoxicity of SiO2 nanoparticles were also determined in HT29 human intestine cells. The results showed that SiO2-25 nm and SiO2-100 nm induced cytotoxic and genotoxic effects after a 24 h exposure. However, regarding cell viability and genotoxicity, nanoparticles (SiO2-100 nm) displayed an inversely proportional, dose-dependent effect. That is, the higher the dose of SiO2-100 nm used then the lower the cytotoxic and genotoxic effects observed.200 In an additional study, the uptake of colloidal SiO2 nanoparticles (15 and 55 nm) in Caco-2 cells was determined. The results indicated size- and concentration-dependent effects on cell death and chromosome damage following exposure to nanoparticles, concomitantly with generation of ROS with smaller particles being the most potent. The smaller particles also increased pro-inflammatory IL-8 secretion at the highest tested dose (32 μg/mL). All nanoparticles localized within the cytoplasm and not the nucleus suggesting observed genotoxic effects were likely mediated through oxidative stress rather than a direct DNA interaction.201,202
Cecropia pachystachya Trécul: identification, isolation of secondary metabolites, in silico study of toxicological evaluation and interaction with the enzymes 5-LOX and α-1-antitrypsin
Published in Journal of Toxicology and Environmental Health, Part A, 2022
Penina Sousa Mourão, Rafael de Oliveira Gomes, Clara Andrezza Crisóstomo Bezerra Costa, Orlando Francisco da Silva Moura, Herbert Gonzaga Sousa, George Roberto Lemos Martins Júnior, Danniel Cabral Leão Ferreira, Antônio Luiz Martins Maia Filho, Johnnatan Duarte de Freitas, Mahendra Rai, Francisco Das Chagas Alves Lima, Antonio Euzébio Gourlart Santana, Mariana Helena Chaves, Wellington Dos Santos Alves, Valdiléia Teixeira Uchôa
It is necessary to achieve a therapeutic concentration of drug administered orally that reaches the hepatic portal vein and thus obtains a more effective action to treat diseases (Souza, Freitas, and Storpirtis 2007). With use of HIA analysis, which is based upon the sum of the degree of absorption and bioavailability observed through excretion of feces, bile and urine (Bastos et al. 2020) it is possible to identify the potential of each substance to act as a beneficial agent. In vitro culture model with CaCo-2 cells, cells extracted from human colon adenocarcinoma, are used to determine the absorption of orally administered drugs by passive transport (transcellular and paracellular) in humans and aids in the research of molecules with a possible therapeutic action because this allows prediction of absorption of these molecules into the human body (Bastos et al. 2020; Souza, Freitas, and Storpirtis 2007).
Zinc(II)-Schiff base complex functionalized on gold nanospheres: synthesis, characterization, anticancer study and interaction with proteins
Published in Journal of Coordination Chemistry, 2022
Yin Zhuang Ng, Kong Wai Tan, Lip Yong Chung, Fatimah Salim, May Lee Low, Ing Hong Ooi, Foo Win Yip, Chew Hee Ng
The integrity of tight junction could be evaluated by measuring the transepithelial electrical resistance (TEER) across the monolayer [62]. The Caco-2 cells were grown in transwell insert for 21 days and the TEER value was monitored until it reached a plateau (between 55 and 60 Ω cm2), indicating the monolayer of Caco-2 cells had grown tightly to achieved tight junctions. For different treatment concentrations (lower than IC50), AuNS-TA-Zn(Sal) was added into the apical chamber. The TEER reading was monitored for each treatment at every 30-min interval for 3 h and the percent change from their initial TEER was plotted and shown in Figure 5.
Influences of simulated gastrointestinal environment on physicochemical properties of gold nanoparticles and their implications on intestinal epithelial permeability
Published in Journal of Environmental Science and Health, Part C, 2019
Xiumei Jiang, Xiaowei Zhang, Patrick Gray, Jiwen Zheng, Timothy R. Croley, Peter P. Fu, Jun-Jie Yin
Cellular uptake of nanoparticles can be affected by many factors, including size, shape, and surface chemistry of the nanoparticles as well as cell type and exposure conditions.32,33 Intestine is the place where most of the digestion and absorption take place. The human epithelial cell line Caco-2 is commonly used for simulating the intestinal epithelial barrier. In this work, we used this cell line to study the cellular uptake of Au NPs that were incubated in GIT fluids. The cellular uptake of Au NPs in Caco-2 cells was characterized by ICP-MS. Au NPs were preincubated in GIT fluids for 2 h before adding to Caco-2 cells. Figure 4a shows a time- and size-dependent cellular uptake of Au NPs in Caco-2 cells with smaller-sized Au NPs taken up by the cells more than larger ones. In addition, compared with the cellular uptake of Au NPs incubated in ddH2O, incubating Au NPs in FaSSGF increased their cellular uptake, while incubating Au NPs in FaSSIF and FeSSIF decreased their cellular uptake (Figure 4b). This is interesting since Au NPs incubated in FaSSGF aggregated due to lower pH and high salt concentration. However, as we discussed before, the aggregated Au NPs in FaSSGF can be re-dispersed in serum-containing cell culture media, possibly by adsorption of proteins in the serum-containing cell culture medium. For Au NPs incubated in FaSSIF and FeSSIF, which already adsorbed proteins/enzymes on their surface when they were incubated in FaSSIF and FeSSIF, their abilities to adsorb thiol-containing biomolecules in serum-containing media are reduced. Protein corona formed by various proteins adsorbing onto NPs could affect the cellular uptake of the NPs.34,35 The simulated GIT fluids incubation of Au NPs may influence the protein adsorption, and thus affect the cellular uptake of Au NPs in Caco-2 cells.