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• W2077261033 abstract "Hexanediol diacrylate cross-linked oligoethylenimine (OEI-HD) is a non-viral polymeric vector designed to deliver siRNA. To achieve safe and effective in vivo siRNA delivery using this vector, the polyplex must have sufficient colloidal stability if administered intravenously or nebulized for delivery by the pulmonary route. In this study, polyplexes from OEI-HD and siRNA were formulated for aerosol-based lung delivery, regarding their colloidal stability, optimal particle size, and in vitro biological activity. Herein, we describe how these properties are dependent upon the polymer-to siRNA weight ratios, buffer composition they were complexed in, PEG-grafting, and the addition of commercial lung surfactants and/or non-ionic surfactants to the formulation. Lastly, the effects of nebulization of the formulation into aerosol droplets, on the polyplex particle size and transfection efficiency, were evaluated. Polyplex size was monitored for up to 2 h after polyplex formation to determine the extent of aggregation and final particle sizes when stability was achieved. Our results suggest that PEG-grafting and polyethylenimine-PEG mixing were effective in achieving colloidal stability in isotonic saline buffers. In addition, colloidal stability was achieved in isotonic glucose buffers using commercially available non-ionic surfactant Pluronic™ P68 or the lung-derived surfactant Alveofact™. The smallest particle size, 140 nm, was obtained with Pluronic™ F68. For transfection efficiency, both Alveofact™ and Pluronic™ F68 achieved equal or better transfection when added to the OEI-HD/siRNA polyplexes. For long term storage of OEI-HD/siRNA formulations, we propose a lyophilization method that created in situ polyplexes upon addition of water. Preparation of OEI-HD/siRNA polyplexes by this method allowed dry storage at room temperature for up to the 3 months. In conclusion, we have identified approaches to achieve formulation and colloidal stability of OEI-HD/siRNA complexes, a step toward successful application of polyplexes for in vivo siRNA delivery." @default.
• W2077261033 created "2016-06-24" @default.
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• W2077261033 date "2012-01-01" @default.
• W2077261033 modified "2023-10-03" @default.
• W2077261033 title "Factors influencing polycation/siRNA colloidal stability toward aerosol lung delivery" @default.
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• W2077261033 doi "https://doi.org/10.1016/j.ejpb.2011.08.008" @default.
• W2077261033 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21924355" @default.
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