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Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination
Núria Puigmal1,2,3,4, Víctor Ramos1, Natalie Artzi2,3,4
1Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià, Universitat Ramon Llull, 08017 Barcelona, Spain.
Novel poly(β-amino ester)s (PBAEs) enhance nucleic acid vaccine delivery through the skin. These vectors target skin immune cells, improving vaccine efficacy and offering a transdermal alternative to injections.
Area of Science:
- Biomaterials Science
- Vaccinology
- Nanotechnology
Background:
- Nucleic acid vaccines are crucial for infectious diseases and cancer.
- Transdermal delivery leverages the skin's immune cells for enhanced responses.
- Efficient delivery vectors are needed for transdermal nucleic acid vaccine strategies.
Purpose of the Study:
- To develop novel poly(β-amino ester)s (PBAEs) for transdermal nucleic acid vaccine delivery.
- To target antigen-presenting cells (APCs) in the skin using modified PBAE vectors.
- To evaluate the efficacy of PBAE vectors for gene delivery via transdermal devices.
Main Methods:
- Synthesized a library of PBAE vectors with oligopeptide termini and mannose ligands.
- Assessed in vitro transfection efficiency of PBAE vectors in human cells.
- Incorporated top-performing PBAE candidates into polyelectrolyte films for microneedle application.
Main Results:
- Oligopeptide-terminated PBAEs significantly improved cell-specific transfection (10-fold increase over controls).
- Mannose inclusion in PBAE backbones further enhanced transfection and gene expression in APCs.
- PBAE-based polyelectrolyte films on microneedles enabled efficient surface gene transfer.
Conclusions:
- Modified PBAEs are highly effective vectors for transdermal nucleic acid delivery.
- Targeted delivery to skin APCs via PBAEs boosts potential vaccine efficacy.
- PBAE-based transdermal systems offer a promising alternative to hypodermic vaccination.
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