Use of Cell-Penetrating Peptides to Enhance Delivery Performance
Surface modification, as presented in Chaps. 14 and 15 , is one of the commonly used strategies in enhancing the chemical and biological properties of a carrier for systemic therapeutics delivery. Apart from enhancing the stability of the carrier or ext
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Use of Cell-Penetrating Peptides to Enhance Delivery Performance Toru Miwa and Kazuhito Tomizawa
Abstract Surface modification, as presented in Chaps. 14 and 15, is one of the commonly used strategies in enhancing the chemical and biological properties of a carrier for systemic therapeutics delivery. Apart from enhancing the stability of the carrier or extending the residence time of the carrier in plasma, once the carrier reaches a target cell, surface modification can enhance the internalization of the carrier into the cell for action. One method of achieving this is to decorate the carrier surface with the cell-penetrating peptide (CPP), which is a peptide that can import large cargoes across nuclear membrane. In this chapter, we will use hearing loss as an example to illustrate the possible use of the CPP, namely poly-arginine (6–12 residues), to enhance cellular internalization of an exogenous agent. Though the short half-life and non-specific transduction of CPP are some drawbacks of using CPP in carrier design, recent studies have already provided some clues for overcoming these problems, and have shed light on the use of CPPs for design of systemic delivery systems in the future. Keywords Sensorineural hearing loss (SNHL) · Cell-penetrating peptides (CPPs) · Embryonic inner ear · Adult inner ear
T. Miwa (B) Department of Otolaryngology-Head and Neck Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, 2-4-20 Ougimaci, Kita-ku, Osaka 5308084, Japan e-mail: [email protected] Department of Otolaryngology-Head and Neck Surgery, Kyoto University, 54 Shogoin, Kawahara-cho, Sakyo-ku, Kyoto 6068507, Japan K. Tomizawa Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuoku, Kumamoto 860-0811, Japan © Springer Nature Switzerland AG 2020 W.-F. Lai (ed.), Systemic Delivery Technologies in Anti-Aging Medicine: Methods and Applications, Healthy Ageing and Longevity 13, https://doi.org/10.1007/978-3-030-54490-4_17
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T. Miwa and K. Tomizawa
16.1 Introduction Over the years, different methods have been proposed for enhancing the efficiency of cellular uptake. One of the methods is the use of the cell-penetrating peptide (CPP), which is a peptide that can import large cargoes across nuclear membrane. To demonstrate the possible use of CPP in carrier optimization for enhanced delivery performance, hearing loss will be used as a model. There are two reasons for this. The first one is because the model of hearing loss is highly accessible for local intervention administration. This facilitates the monitoring of the intervention process. Another reason is because hearing loss is not only an age-related symptom, it may also affect adults and even children. In fact, according to the most recent estimate by the World Health Organization, about 360 million people (approximately 5.3% global population) suffer from disabling hearing loss (World Health Organization 2019). Hearing loss in children has been repeatedly demonstrated to affect academic, behavio
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