title: Controlling in vivo stability and biodistribution in electrostatically assembled nanoparticles for systemic delivery.
abstract: This paper demonstrates the generation of systemically deliverable layer-by-layer (LbL) nanoparticles for cancer applications. LbL-based nanoparticles designed to navigate the body and deliver therapeutics in a programmable fashion are promising new and alternative systems for drug delivery, but there have been very few demonstrations of their systemic delivery in vivo due to a lack of knowledge in building LbL nanofilms that mimic traditional nanoparticle design to optimize delivery. The key to the successful application of these nanocarriers in vivo requires a systematic analysis of the influence of film architecture and adsorbed polyelectrolyte outer layer on their pharmacokinetics, which has thus far not been examined for this new approach to nanoparticle delivery. Herein, we have taken the first steps in stabilizing and controlling the systemic distribution of multilayer nanoparticles. Our findings highlight the unique character of LbL systems; the electrostatically assembled nanoparticles gain increased stability in vivo with larger numbers of deposited layers, and the final layer adsorbed generates a critical surface cascade, which dictates the surface chemistry and biological properties of the nanoparticle. This outer polyelectrolyte layer dramatically affects not only the degree of nonspecific particle uptake, but also the nanoparticle biodistribution. For hyaluronic acid (HA) outer layers, a long blood elimination half-life (∼9 h) and low accumulation (∼10-15% recovered fluorescence/g) in the liver were observed, illustrating that these systems can be designed to be highly appropriate for clinical translation.
authors.affiliation: The Koch Institute for Integrative Cancer Research at MIT, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Poon
authors.forename: Jong Bum
authors.initials: JB
authors.lastname: Lee
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Morton
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D000327:Adsorption; D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D008099:Liver / Q000187:drug effects; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D055672:Static Electricity; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D004364:Pharmaceutical Preparations; D006820:Hyaluronic Acid