Controlling the surface‐mediated release of DNA using ‘mixed multilayers’

Abstract

We report the design of erodible ‘mixed multilayer’ coatings fabricated using plasmid DNA and combinations of both hydrolytically degradable and charge‐shifting cationic polymer building blocks. Films fabricated layer‐by‐layer using combinations of a model poly(β‐amino ester) (polymer 1) and a model charge‐shifting polymer (polymer 2) exhibited DNA release profiles that were substantially different than those assembled using DNA and either polymer 1 or polymer 2 alone. In addition, the order in which layers of these two cationic polymers were deposited during assembly had a profound impact on DNA release profiles when these materials were incubated in physiological buffer. Mixed multilayers ∼225 nm thick fabricated by depositing layers of polymer 1/DNA onto films composed of polymer 2/DNA released DNA into solution over ∼60 days, with multi‐phase release profiles intermediate to and exhibiting some general features of polymer 1/DNA or polymer 2/DNA films (e.g., a period of rapid release, followed by a more extended phase). In sharp contrast, ‘inverted’ mixed multilayers fabricated by depositing layers of polymer 2/DNA onto films composed of polymer 1/DNA exhibited release profiles that were almost completely linear over ∼60‐80 days. These and other results are consistent with substantial interdiffusion and commingling (or mixing) among the individual components of these compound materials. Our results reveal this mixing to lead to new, unanticipated, and useful release profiles and provide guidance for the design of polymer‐based coatings for the local, surface‐mediated delivery of DNA from the surfaces of topologically complex interventional devices, such as intravascular stents, with predictable long‐term release profiles.

Enzyme Prodrug Therapy Achieves Site-Specific, Personalized Physiological Responses to the Locally Produced Nitric Oxide

“…Polymers used in this work were poly­(ethyleneimine) (PEI, ∼25 000 Da, branched), poly­(sodium-4-styrene sulfonate) (PSS, ∼70 000 Da), poly­(methacrylic acid) (PMA, ∼18 500 Da), poly­(acrylic acid) (PAA, ∼28 300 Da), dextran sulfate (200 000 Da), chrondoitin sulfate (5–100 kDa), hyaluronic acid (HA, low: 15 000–30 000 Da, high: 1.5–1.8 × 10 6 Da), alginate (ALG, 12 000–40 000 Da), DNA (from herring testes), poly­(diallyldimethylammonium chloride) (100 000–200 000 Da), poly- l -lysine (30 000–70 000 Da), poly- l -arginine hydrochloride (PLA, 15 000–70 000 Da), poly- l -histidine (PLH, 5000–25 000 Da), poly­(allylamine hydrochloride) (PAH, ∼15 000 and 17 500 Da), chitosan (Chi, 190 000–310 000 Da), biodegradable polyamidoester (∼8300 Da), and protamine sulfate (PRT, ∼5100 Da). Phosphate-buffered saline (PBS) and 4-(2-hydroxyethyl)­piperazine-1-ethane-sulfonic acid (HEPES) of 10 mM containing 150 mM NaCl in MQ with pH 7.4 were used as buffers.…”

Polyelectrolyte multilayers for bio‐applications: recent advancements

“…Originated from planar surfaces, the multilayers topologically organised in the shape of hollow spheres became attractive systems for drug-delivery applications for their employment as drug carriers [18,19]. In addition to this, PEM offers a wide spectrum of permeability for different species ranging from small ions to large drug molecules by stimulating the physical and chemical parameter of the surroundings [20][21][22]. Fig.…”

Engineering Degradation Rate of Polyphosphazene-Based Layer-by-Layer Polymer Coatings

“…Degradable LbL coatings offer a versatile platform to customize the release profiles of encapsulated drugs. Previous work in degradable LbL coatings has often focused on the family of poly(β-amino esters), which were assembled with therapeutic molecules such as plasmid DNA, siRNA, enzymes, antibiotics, and growth factors [19][20][21][22][23][24][25][26][27][28]. These LbL 2 of 17 systems using poly(β-amino esters) are cationic and degrade from hours to months, with some control of the degradation rate via synthetic modification of the backbone [29,30].…”