Replacement techniques to reduce animal experiments in drug and nanoparticle development

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Journal of Pharmaceutical Investigation (2020) 50:327–335 https://doi.org/10.1007/s40005-020-00487-8

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Replacement techniques to reduce animal experiments in drug and nanoparticle development Ik Sup Jin1 · Moon Sup Yoon1 · Chun‑Woong Park1 · Jin Tae Hong1 · Youn Bok Chung1 · Jin‑Seok Kim2 · Dae Hwan Shin1 Received: 28 February 2020 / Accepted: 15 April 2020 / Published online: 20 April 2020 © The Korean Society of Pharmaceutical Sciences and Technology 2020

Abstract Background  Animals have been used for the testing of new drugs and nanoparticles to determine their safety and effectiveness before application in humans. Numerous drugs and nanoparticles have been developed through animal tests, and development in medical nanotechnology is progressing rapidly. However, a good experiment requires many animals. The primary measures to reduce animal experiments include reducing the number of animals used in each experiment and replacing laboratory animals with inanimate, cellular, or inferior animals to reduce sacrifices. Area covered  Developing nanoparticles using simulations rather than experiments may be another alternative. Instead of animals, human cells or animal-derived organs, tissues, or cells could be used in experiments. These methods allow rapid toxicity and efficacy testing at low cost. However, the disadvantage of these methods is that they cannot accurately replicate the complex interrelationships between human organs, biological reactions to specific routes of administration, or toxicity of substances resulting from metabolic processes. To overcome these shortcomings of in vitro tests, new technologies such as organoids and organ-on-chips are progressing. These can be used to quickly examine the efficacy of newly developed drugs and nanoparticles and can be useful in developing patient-tailored agents. Expert opinion  These technologies offer some promise but it is still difficult to entirely replace animal experiments. However, the scope of methods to replace experimental animals is widening, suggesting the potential to refine, reduce, and ultimately replace animal testing. Keywords  Animal experiment replacement · Biochip · Organoid · Drug development · Animal ethics · Nanoparticle

Introduction The development of medicines based on nanotechnology has been progressing over decades. It began in 1965 with liposomes, the first example of lipid vesicles, which have had a substantial impact on the treatment of human diseases and continue to be rapidly developed for new application (Bangham et al. 1965; Farokhzad and Langer 2006). Since then, various nanocarriers, such as micelles, liposomes, ackn and cyclodextrins, have been widely studied and developed. * Dae Hwan Shin [email protected] 1



College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea



Drug Information Research Institute, College of Pharmacy, Sookmyung Women’s University, Seoul 04310, Republic of Korea

2

For example, various studies have demonstrated that using micelles and liposomes as carriers not