Programmable self-regulated molecular buffers for precise sustained drug delivery

Arnaud Desrosiers, Rabeb Mouna Derbali, Sami Hassine, Jérémie Berdugo, Valérie Long, Dominic Lauzon, Vincent De Guire, Céline Fiset, Luc DesGroseillers, Jeanne Leblond Chain and Alexis Vallée-Bélisle ()
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Arnaud Desrosiers: Université de Montréal
Rabeb Mouna Derbali: Université de Montréal
Sami Hassine: Université de Montréal
Jérémie Berdugo: Université de Montréal
Valérie Long: Université de Montréal
Dominic Lauzon: Université de Montréal
Vincent De Guire: Maisonneuve-Rosemont Hospital, Optilab-CHUM Laboratory Network
Céline Fiset: Université de Montréal
Luc DesGroseillers: Université de Montréal
Jeanne Leblond Chain: Univ. Bordeaux, CNRS, INSERM, ARNA
Alexis Vallée-Bélisle: Université de Montréal

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Unlike artificial nanosystems, biological systems are ideally engineered to respond to their environment. As such, natural molecular buffers ensure precise and quantitative delivery of specific molecules through self-regulated mechanisms based on Le Chatelier’s principle. Here, we apply this principle to design self-regulated nucleic acid molecular buffers for the chemotherapeutic drug doxorubicin and the antimalarial agent quinine. We show that these aptamer-based buffers can be programmed to maintain any specific desired concentration of free drug both in vitro and in vivo and enable the optimization of the chemical stability, partition coefficient, pharmacokinetics and biodistribution of the drug. These programmable buffers can be built from any polymer and should improve patient therapeutic outcome by enhancing drug activity and minimizing adverse effects and dosage frequency.

Date: 2022
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DOI: 10.1038/s41467-022-33491-7

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