TY - JOUR
T1 - Designing Polyelectrolyte Microneedles Based on Borylated Poly(β-aminoester) Polymers To Enhance Transdermal pH-Controlled Delivery of Nucleic Acids
AU - González-Sáenz, Patricia
AU - Cosialls, Raúl
AU - Texidó, Robert
AU - Dols-Pérez, Aurora
AU - Cuenca, Ana Belén
AU - Borrós, Salvador
AU - Fornaguera, Cristina
N1 - Publisher Copyright:
© 2024 The Authors. Published by American Chemical Society.
PY - 2024/8
Y1 - 2024/8
N2 - The use of transdermal delivery for nucleic acid administration is an interesting approach to overcoming limitations of systemic administration routes, such as first-pass effects, the painful needle injection, or their poor biodistribution. Thus, the use of a microneedle-based patch could represent a turning point for nucleic acid delivery, thanks to the possibility of self-administration of the actives in a painless and easy procedure. However, the design of transdermal systems with a higher degree of precision release is a clear need that has not been fully resolved. Committed to tackling this challenge, we present here a microneedle patch that involves a smart delivery system supported by the well-established ability of boronic acid to interact with carbohydrates in a pH-dependent manner. This system builds up a multilayer structure over a solid microneedle platform whose surface has been modified to immobilize glucosamine units that are able to interact with an oligopeptide-end terminated poly(β-aminoester) that presents a 4-carboxy-3-fluorophenylboronic acid (Bor-pBAE). Thus, sequential layers of the Bor-pBAE and plasmid DNA have been assembled, thanks to the ability of the polymer to interact with the nucleic acid at a basic pH and then gradually release the plasmid under two different conditions of pH (the physiological pH = 7.4 and the acidic pH = 5.1). We set up the design and implementation of this first proof of concept while demonstrating microneedles' safety and functionality. Additionally, we have shown the efficacy of the construct to express the encoded genes in model cell lines. In conclusion, we have established the basis to confirm that this generation of borylated poly(β-aminoesters) holds great promise as a transdermal local nucleic acid delivery system.
AB - The use of transdermal delivery for nucleic acid administration is an interesting approach to overcoming limitations of systemic administration routes, such as first-pass effects, the painful needle injection, or their poor biodistribution. Thus, the use of a microneedle-based patch could represent a turning point for nucleic acid delivery, thanks to the possibility of self-administration of the actives in a painless and easy procedure. However, the design of transdermal systems with a higher degree of precision release is a clear need that has not been fully resolved. Committed to tackling this challenge, we present here a microneedle patch that involves a smart delivery system supported by the well-established ability of boronic acid to interact with carbohydrates in a pH-dependent manner. This system builds up a multilayer structure over a solid microneedle platform whose surface has been modified to immobilize glucosamine units that are able to interact with an oligopeptide-end terminated poly(β-aminoester) that presents a 4-carboxy-3-fluorophenylboronic acid (Bor-pBAE). Thus, sequential layers of the Bor-pBAE and plasmid DNA have been assembled, thanks to the ability of the polymer to interact with the nucleic acid at a basic pH and then gradually release the plasmid under two different conditions of pH (the physiological pH = 7.4 and the acidic pH = 5.1). We set up the design and implementation of this first proof of concept while demonstrating microneedles' safety and functionality. Additionally, we have shown the efficacy of the construct to express the encoded genes in model cell lines. In conclusion, we have established the basis to confirm that this generation of borylated poly(β-aminoesters) holds great promise as a transdermal local nucleic acid delivery system.
KW - borylated poly(β-aminoester)
KW - gene delivery
KW - microneedles
KW - multilayered coating
KW - polyelectrolytes
UR - http://www.scopus.com/inward/record.url?scp=85199472314&partnerID=8YFLogxK
UR - http://hdl.handle.net/20.500.14342/4598
U2 - 10.1021/acsapm.4c00969
DO - 10.1021/acsapm.4c00969
M3 - Article
AN - SCOPUS:85199472314
SN - 2637-6105
VL - 6
SP - 8842
EP - 8855
JO - ACS Applied Polymer Materials
JF - ACS Applied Polymer Materials
IS - 15
ER -