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Molecules 2018, 23(9), 2318; https://doi.org/10.3390/molecules23092318

Amino Acids in the Development of Prodrugs

1
Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
2
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal
3
Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
4
Department of Molecular Pathology and Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
5
LAQV&REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
6
SpiroChem AG, Rosental Area, WRO-1074-3, Mattenstrasse 24, 4058 Basel, Switzerland
*
Author to whom correspondence should be addressed.
Received: 23 July 2018 / Revised: 30 August 2018 / Accepted: 6 September 2018 / Published: 11 September 2018
(This article belongs to the Section Chemical Biology)

Abstract

Although drugs currently used for the various types of diseases (e.g., antiparasitic, antiviral, antibacterial, etc.) are effective, they present several undesirable pharmacological and pharmaceutical properties. Most of the drugs have low bioavailability, lack of sensitivity, and do not target only the damaged cells, thus also affecting normal cells. Moreover, there is the risk of developing resistance against drugs upon chronic treatment. Consequently, their potential clinical applications might be limited and therefore, it is mandatory to find strategies that improve those properties of therapeutic agents. The development of prodrugs using amino acids as moieties has resulted in improvements in several properties, namely increased bioavailability, decreased toxicity of the parent drug, accurate delivery to target tissues or organs, and prevention of fast metabolism. Herein, we provide an overview of models currently in use of prodrug design with amino acids. Furthermore, we review the challenges related to the permeability of poorly absorbed drugs and transport and deliver on target organs. View Full-Text
Keywords: amino acid transport; drug delivery; prodrug design; stability studies; in vitro and in vivo assays amino acid transport; drug delivery; prodrug design; stability studies; in vitro and in vivo assays
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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MDPI and ACS Style

Vale, N.; Ferreira, A.; Matos, J.; Fresco, P.; Gouveia, M.J. Amino Acids in the Development of Prodrugs. Molecules 2018, 23, 2318.

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