Aerosol formation of biocompatible micro/nanoparticles.

摘要

Electrohydrodynamic spraying (EHDS or electrospray for short) is an aerosol technique that uses an electric field to break a liquid stream into fine particles. A high electric voltage is applied to a liquid and introduces electrical stress on its surface. When the electrical stress overcomes the surface tension, a Taylor cone is formed followed by a liquid jet. The jet is not stable and breaks into fine particles. Electrospray has attracted lots of research interest because of its ability to continuously produce monodisperse micro/nanoparticles, with little damage to the materials and a relatively low energy input.;Electrospray is most widely known for its use in electrospray ionization mass-spectrometry (ESI-MS). Recently, electrospray has been developed to assist the production and characterization of inorganic particles, to form coatings or on-demand patterns on surfaces and to create structured micro/nanoparticles for actives encapsulation and controlled release.;Although significant research progress has been made, the development of electrospray for bioapplications is mostly limited to ESI-MS. In this work we explore the potential bioapplications of electrospray, including dispersing hydrophobic compounds (cholesterol as model hydrophobic compounds) into nanoparticles for hydrophobic drug delivery or cell culture medium supplementation, creating DNA/Polyethyleneimine (PEI) polyplexes for pulmonary gene delivery and producing oligonucleotide (ODN) encapsulated lipoplex nanoparticles for parenteral gene delivery.;To date we have demonstrated the feasibility of dispersing cholesterol in liquid media with an electrospray apparatus using a single needle. We first tested the biological activity of cholesterol nanoparticles against a wild type cholesterol auxotroph NS0 cell line and demonstrated that electrosprayed cholesterol formulations can maintain long term cell growth. We then optimized the formulations for continuous batch and fed-batch cultures of another NS0 cell line, that produces a therapeutic protein, and increased the product titer by ∼60%.;Another electrospray apparatus using concentric needles was developed to prepare DNA/PEI polyplexes for pulmonary gene delivery and ODN encapsulated lipoplex nanoparticles for parenteral gene delivery. We found that the electrosprayed DNA/PEI polyplexes have higher delivery efficiencies than those prepared by bulk mixing. The ODN encapsulated lipoplex nanoparticles produced by electrospray were successfully taken up by K562 cells and the bcl-2 expression was down regulated.