Spray‐Dried Nanoparticle‐in‐Microparticle Delivery Systems (NiMDS) for Gene Delivery, Comprising Polyethylenimine (PEI)‐Based Nanoparticles in a Poly(Vinyl Alcohol) Matrix. Issue 12 (12th February 2018)

• Record Type: Journal Article
• Authors: Schulze, Jan; Kuhn, Stephanie; Hendrikx, Stephan; Schulz‐Siegmund, Michaela; Polte, Tobias; Aigner, Achim
• Is Part Of: Small. Volume 14:Issue 12(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-02-12
• Subjects: nanoparticle‐in‐microparticle delivery systems -- poly(vinyl alcohol) -- polyethylenimine -- PVA microparticles -- spray drying; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201701810
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Nucleic acid‐based therapies rely on efficient formulations for nucleic acid protection and delivery. As nonviral strategies, polymeric and lipid‐based nanoparticles have been introduced; however, biological efficacy and biocompatibility as well as poor storage properties due to colloidal instability and their unavailability as ready‐to‐use systems are still major issues. Polyethylenimine is the most widely explored and promising candidate for gene delivery. Polyethylenimine‐based polyplexes and their combination with liposomes, lipopolyplexes, are efficient for DNA or siRNA delivery in vitro and in vivo. In this study, a highly potent spray‐dried nanoparticle‐in‐microparticle delivery system is presented for the encapsulation of polyethylenimine‐based polyplexes and lipopolyplexes into poly(vinyl alcohol) microparticles, without requiring additional stabilizing agents. This easy‐to‐handle gene delivery device allows prolonged nanoparticle storage and protection at ambient temperature. Biological analyses reveal further advantages regarding profoundly reduced cytotoxicity and enhanced transfection efficacies of polyethylenimine‐based nanoparticles from the nanoparticle‐in‐microparticle delivery system over their freshly prepared counterparts, as determined in various cell lines. Importantly, this nanoparticle‐in‐microparticle delivery system is demonstrated as ready‐to‐use dry powder to be an efficient device for the inhalative delivery of polyethylenimine‐based lipopolyplexes in vivo, as shown by transgene expression in mice after only one administration. Abstract : Polyethylenimine‐based polyplexes and lipopolyplexes are efficient and biocompatible for DNA or siRNA delivery. A highly potent spray dried nanoparticle‐in‐microparticle delivery system for their encapsulation into poly(vinyl alcohol)‐microparticles is presented. This easy‐to‐handle gene delivery device allows prolonged nanoparticle storage and protection, shows profoundly reduced cytotoxicity and enhanced transfection efficacies, and is a ready‐to‐use dry powder for inhalative delivery.