Polyelectrolyte Multilayered Nanoparticles: Using Nanolayers for Controlled and Targeted Systemic Release

Abstract

The simplicity of layer-by-layer (LbL) assembly [1] – a method that involves the alternating adsorption from water of two or more polymers or other multivalent species with complementary interactions – has led to a recent and greatly accelerated growth of new drug delivery systems that take advantage of the mild aqueous conditions and high drug loadings that are possible using this method [2–4]. The ability to incorporate a broad range of therapeutic molecules at meaningful drug loadings, from small molecule drugs to sensitive biologics such as peptides, proteins, growth factors and nucleic acids has contributed significantly to this revolution. Furthermore, there is significant promise in the ability to release multiple drugs from a singular nanoscale thin film with independent release profiles of each drug tuned to the desired pharmacokinetics [5]. This promise is furthered by recent demonstrations that multilayer thin films can regulate not only relative release behavior, but yield time-sequenced release from surfaces [6,7]. Many exciting new applications involve the use of coated micron-sized particles and microcapsules that are of interest for localized release biomaterials, cellular mimics and the targeting of cells that readily engage with micronscale particles, such as macrophages and certain immunological cells [8]. The advantages described above are highly relevant to the goals of targeted nanomedicine, in which the nanoscale nature of the delivery vehicle itself enables accumulation of drug carriers in pathological tissues and access to tissues via various modes of cell penetration and entry. The concept of generating drug delivery nanoparticles that provide controlled, staged and/or triggered release of different drugs at appropriate points in the body is highly attractive to the treatment of cancer, infectious disease, lung, cardiovascular