Designing Polyelectrolyte Microneedles Based on Borylated Poly(β-aminoester) Polymers To Enhance Transdermal pH-Controlled Delivery of Nucleic Acids

Patricia González-Sáenz, Raúl Cosialls, Robert Texidó, Aurora Dols-Pérez, Ana Belén Cuenca, Salvador Borrós, Cristina Fornaguera

Producció científica: Article en revista indexadaArticleAvaluat per experts

Resum

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.

Idioma originalAnglès
Pàgines (de-a)8842-8855
Nombre de pàgines14
RevistaACS Applied Polymer Materials
Volum6
Número15
DOIs
Estat de la publicacióPublicada - d’ag. 2024

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