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Controlling the surface-mediated release of DNA using 'mixed multilayers'.

Visham Appadoo1, Matthew C D Carter1, David M Lynn2

  • 1Dept. of Chemistry, 1101 University Avenue University of Wisconsin-Madison Madison WI 53706.

Bioengineering & Translational Medicine
|December 17, 2016
PubMed
Summary

New polymer coatings with plasmid DNA offer controlled, long-term DNA release. The order of polymer layers significantly impacts release profiles, enabling predictable delivery from medical devices.

Keywords:
gene deliverylayer‐by‐layermultilayerspolymerssurfacesthin films

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Area of Science:

  • Materials Science
  • Biotechnology
  • Polymer Chemistry

Background:

  • Controlled drug delivery systems are crucial for localized and sustained therapeutic agent release.
  • Plasmid DNA delivery requires advanced biomaterials that ensure stability and controlled release kinetics.
  • Layer-by-layer assembly is a versatile technique for fabricating complex multilayered structures.

Purpose of the Study:

  • To design and fabricate novel erodible 'mixed multilayer' coatings using plasmid DNA and combinations of degradable and charge-shifting cationic polymers.
  • To investigate the impact of polymer order and composition on DNA release profiles from these coatings.
  • To evaluate the potential of these coatings for predictable, long-term DNA delivery from medical devices.

Main Methods:

  • Fabrication of multilayer films using plasmid DNA and two types of cationic polymers: a hydrolytically degradable poly(β-amino ester) (polymer 1) and a charge-shifting polymer (polymer 2).
  • Layer-by-layer assembly was employed, with variations in the deposition order of polymer 1/DNA and polymer 2/DNA layers.
  • DNA release kinetics were monitored over extended periods (60-80 days) in physiological buffer.

Main Results:

  • Mixed multilayer coatings exhibited distinct DNA release profiles compared to single-polymer coatings.
  • The order of polymer layer deposition profoundly influenced release kinetics: 'inverted' mixed multilayers showed nearly linear release over 60-80 days.
  • Results suggest significant interdiffusion and mixing of components within the mixed multilayers, leading to unique release behaviors.

Conclusions:

  • The design of 'mixed multilayer' coatings offers tunable and predictable DNA release profiles.
  • Intermixing of polymer components is key to achieving desired release kinetics, such as linear release over extended periods.
  • These findings provide a foundation for developing advanced polymer coatings for surface-mediated DNA delivery from interventional devices like stents.