Designing Polyelectrolyte Microneedles Based on Borylated Poly(β-aminoester) Polymers To Enhance Transdermal...

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Molecular Biology

Background:

• Transdermal nucleic acid delivery offers advantages over systemic routes, avoiding first-pass effects and needle pain.
• Current transdermal systems lack precise control over drug release, a significant challenge.
• Microneedle patches provide a potential solution for painless, self-administered nucleic acid delivery.

Purpose of the Study:

• To develop and validate a novel microneedle patch for precise, pH-dependent transdermal nucleic acid delivery.
• To engineer a smart delivery system utilizing boronic acid-carbohydrate interactions.
• To demonstrate the safety, functionality, and efficacy of the developed microneedle system.

Main Methods:

• Fabrication of a microneedle platform with immobilized glucosamine units.
• Modification of poly(β-aminoester) with 4-carboxy-3-fluorophenylboronic acid (Bor-pBAE).
• Assembly of sequential layers of Bor-pBAE and plasmid DNA on microneedles.
• In vitro assessment of pH-dependent release and gene expression in model cell lines.

Main Results:

• Successful construction and demonstration of a multilayer microneedle patch.
• Controlled, pH-dependent release of plasmid DNA was achieved at physiological (7.4) and acidic (5.1) pH.
• The microneedle system exhibited safety, functionality, and efficacy in delivering genes for expression in cell lines.

Conclusions:

• Borylated poly(β-aminoesters) are promising for developing advanced transdermal nucleic acid delivery systems.
• The pH-responsive microneedle patch offers a precise and controllable method for local nucleic acid delivery.
• This technology represents a significant advancement in painless, self-administered nucleic acid therapeutics.