Replacement techniques to reduce animal experiments in drug and nanoparticle development

Jin, Ik Sup; Yoon, Moon Sup; Park, Chun‐Woong; Hong, Jin Tae; Chung, Youn Bok; Kim, Jinseok; Shin, Dae Hwan

doi:10.1007/s40005-020-00487-8

Cited by 9 publications

(6 citation statements)

References 62 publications

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“…In vivo studies with animals can be time‐consuming and costly. [ 51,52 ] As many assays or transplantations are not feasible in humans, especially in the human brain, [ 53 ] reliable high‐throughput in vitro cellular models—which could permit the safe and controlled testing of dosage, exposure, and various cell types or organ systems in real time physiological or pathological conditions that are relevant to humans—are vital for preclinical experimentation. [ 53,54 ] As organoid‐based models can better recapitulate the physiological microenvironment, spatial complexity, and cellular organization and interactions compared to monolayer cultures, [ 55 ] several others have employed 3D tissue cultures to characterize toxicity and pharmacokinetics in vitro.…”

Section: Discussionmentioning

confidence: 99%

Humanized Biomimetic Nanovesicles for Neuron Targeting

et al. 2021

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Nanovesicles (NVs) are emerging as innovative, theranostic tools for cargo delivery. Recently, surface engineering of NVs with membrane proteins from specific cell types has been shown to improve the biocompatibility of NVs and enable the integration of functional attributes. However, this type of biomimetic approach has not yet been explored using human neural cells for applications within the nervous system. Here, this paper optimizes and validates the scalable and reproducible production of two types of neuron-targeting NVs, each with a distinct lipid formulation backbone suited to potential therapeutic cargo, by integrating membrane proteins that are unbiasedly sourced from human pluripotent stem-cell-derived neurons. The results establish that both endogenous and genetically engineered cell-derived proteins effectively transfer to NVs without disruption of their physicochemical properties. NVs with neuron-derived membrane proteins exhibit enhanced neuronal association and uptake compared to bare NVs. Viability of 3D neural sphere cultures is not disrupted by treatment, which verifies the utility of organoid-based approaches as NV testing platforms. Finally, these results confirm cellular association and uptake of the biomimetic humanized NVs to neurons within rodent cranial nerves. In summary, the customizable NVs reported here enable next-generation functionalized theranostics aimed to promote neuroregeneration.

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Section: Discussionmentioning

confidence: 99%

Humanized Biomimetic Nanovesicles for Neuron Targeting

et al. 2021

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“…Currently, the request to reduce animals for experimental purposes is continuously growing. European policies on animal experimentation are intensely aiming to increase the protection of experimental animals, thus various alternative methods have being developed to achieve this purpose [6]. Even the most advanced in vitro and in silico systems cannot fully simulate complex phenomena such as inflammation, digestion, pathologies, and metabolism.…”

Section: Introductionmentioning

confidence: 99%

Swine intestinal segment perfusion model for the evaluation of nutrients bioaccessibility

et al. 2023

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Nutrition science requires more science-based evidences for the development of effective functional diets. To reduce animals for experimental purposes innovative reliable and informative models, simulating the complex intestinal physiology, are needed. The aim of this study was to develop a swine duodenum segment perfusion model for the evaluation of nutrient bioaccessibility and functionality across time. At the slaughterhouse, one sow intestine was harvested following Maastricht criteria for organ donation after circulatory death (DCD) for transplantation purposes. Duodenum tract was isolated and perfused in sub-normothermic conditions with heterologous blood after cold ischemia induction. Duodenum segment perfusion model was maintained under controlled pressure conditions through extracorporeal circulation for 3 hours. Blood samples from extracorporeal circulation and luminal content samples were collected at regular intervals for the evaluation of glucose concentration by glucometer, minerals (Na+, Ca2+, Mg2+, K+) by ICP-OES, lactate-dehydrogenase and nitrite oxide by spectrophotometric methods. Dacroscopic observation showed peristaltic activity caused by intrinsic nerves. Glycemia decreased over time (from 44.00±1.20 mg/dL to 27.50±0.41; p < 0.01), suggesting glucose utilization by the tissue confirming the organ viability in line with histological examinations. At the end of the experimental period, intestinal mineral concentrations were lower than their level in blood plasma suggesting their bioaccessibility (p < 0.001). A progressive increase of LDH concentration over time was observed in the luminal content probably related to a loss of viability (from 0.32±0.02 to 1.36±0.02 OD; p < 0.05) confirmed by histological findings that revealed a de-epithelization of the distal portion of duodenum. Isolated swine duodenum perfusion model satisfied the criteria for studying bioaccessibility of nutrients, offering a variety of experimental possibilities in line with 3Rs principle.

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“…Organ-on-chip systems have a high potential to improve in vitro studies for new pharmaceutical drug candidates and to accelerate the development of medication [ 1 , 2 ]. At a microscale level, the environment of cells can be precisely controlled, allowing the simulation of physiological conditions of particular cell barriers, such as the blood–brain barrier [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Tissue Barrier-on-Chip: A Technology for Reproducible Practice in Drug Testing

et al. 2022

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One key application of organ-on-chip systems is the examination of drug transport and absorption through native cell barriers such the blood–brain barrier. To overcome previous hurdles related to the transferability of existing static cell cultivation protocols and polydimethylsiloxane (PDMS) as the construction material, a chip platform with key innovations for practical use in drug-permeation testing is presented. First, the design allows for the transfer of barrier-forming tissue into the microfluidic system after cells have been seeded on porous polymer or Si3N4 membranes. From this, we can follow highly reproducible models and cultivation protocols established for static drug testing, from coating the membrane to seeding the cells and cell analysis. Second, the perfusion system is a microscopable glass chip with two fluid compartments with transparent embedded electrodes separated by the membrane. The reversible closure in a clamping adapter requires only a very thin PDMS sealing with negligible liquid contact, thereby eliminating well-known disadvantages of PDMS, such as its limited usability in the quantitative measurements of hydrophobic drug molecule concentrations. Equipped with tissue transfer capabilities, perfusion chamber inertness and air bubble trapping, and supplemented with automated fluid control, the presented system is a promising platform for studying established in vitro models of tissue barriers under reproducible microfluidic perfusion conditions.

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Replacement techniques to reduce animal experiments in drug and nanoparticle development

Cited by 9 publications

References 62 publications

Humanized Biomimetic Nanovesicles for Neuron Targeting

Humanized Biomimetic Nanovesicles for Neuron Targeting

Swine intestinal segment perfusion model for the evaluation of nutrients bioaccessibility

Tissue Barrier-on-Chip: A Technology for Reproducible Practice in Drug Testing

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