Layer-by-Layer Assembly of DNA- and Protein-Containing Films on Microneedles for Drug Delivery to the Skin

Abstract

Microneedle patches contain micron-scale needles coated with bioactive agents for minimally invasive drug delivery to the skin. In this study, we introduce layer-by-layer approaches to the fabrication of ultrathin DNA- and protein-containing polyelectrolyte films (or ‘polyelectrolyte multilayers’, PEMs) on the surfaces of stainless steel microneedles. DNA-containing PEMs were fabricated on microneedles by the alternating deposition of plasmid DNA and a hydrolytically degradable poly(β-amino ester). Protein-containing PEMs were fabricated using sodium poly(styrene sulfonate) (SPS) and bovine pancreatic ribonuclease A (RNase A) conjugated to a synthetic protein transduction domain. Layer-by-layer assembly resulted in ultrathin, uniform, and defect-free coatings on the surfaces of the microneedles, as characterized by fluorescence microscopy. These films eroded and thereby released DNA or protein when incubated in saline or when inserted into porcine cadaver skin, and deposited DNA or protein along the edges of microneedle tracks to depths of ~500 to 600μm. We conclude that PEM-coated microneedles offer a novel and useful approach to the transdermal delivery of DNA- and protein-based therapeutics and could also prove useful in other applications.

Polymeric microneedles for transdermal protein delivery

“…More than 10-fold higher serum IgG titers were observed compared to the free OVA injection, suggesting that this system could be used as a platform for vaccination against emerging infectious pathogens [117]. In addition, Prausnitz and coworkers developed another technique of layer-by-layer deposition of polyelectrolytes, which was used to coat bovine pancreatic ribonuclease A onto the stainless steel MNs [119]. The release of the protein drug was mediated by the hydrolytic degradation of the coating layer after the insertion into the porcine cadaver skin with a depth of around 500 μm.…”

Nanocoating for biomolecule delivery using layer-by-layer self-assembly

“…peri-implant tissue formation 21 ), but may also represent the primary function of the device ( e.g. drug coating on transdermal needles 30 ). Since the coating is designed to control biomolecule release at the implant surface, it is essential that the coating remains integrated with the underlying material.…”

Studies on the thermal properties and flammability of polyamide 6 nanocomposites surface-modified via layer-by-layer deposition of chitosan and montmorillonite

“…Since then, many practical applications of this surface treatment method have been described, such as in electrochromic materials [3][4][5], controlled drug delivery [6,7], composites with barrier properties towards oxygen [8][9][10][11][12], antireflective [13] and waterproof coatings [14][15][16], and antibacterial materials [17][18][19]. In principle, LbL assemblies arise from alternative dipping of substrates in, most often, water-based solutions of polyelectrolytes, which makes this method eco-friendly.…”