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Nanoprecipitation of polymeric nanoparticle micelles based on 2-methacryloyloxyethyl phosphorylcholine (MPC) with 2-(diisopropylamino)ethyl methacrylate (DPA), for intracellular delivery applications

Biodistribution of nanoparticle-based intracellular delivery systems is mediated primarily by particle size and physicochemical properties. As such, overcoming the rapid removal of these by the reticuloendothelial system remains a significant challenge. To date, a number of copolymer nanoparticle sy...

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Autores principales: Salvage, Jonathan P., Thom, Christopher, Lewis, Andrew L., Phillips, Gary J., Lloyd, Andrew W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359341/
https://www.ncbi.nlm.nih.gov/pubmed/25773229
http://dx.doi.org/10.1007/s10856-015-5480-9
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author Salvage, Jonathan P.
Thom, Christopher
Lewis, Andrew L.
Phillips, Gary J.
Lloyd, Andrew W.
author_facet Salvage, Jonathan P.
Thom, Christopher
Lewis, Andrew L.
Phillips, Gary J.
Lloyd, Andrew W.
author_sort Salvage, Jonathan P.
collection PubMed
description Biodistribution of nanoparticle-based intracellular delivery systems is mediated primarily by particle size and physicochemical properties. As such, overcoming the rapid removal of these by the reticuloendothelial system remains a significant challenge. To date, a number of copolymer nanoparticle systems based on 2-methacryloyloxyethyl phosphorylcholine (MPC) with 2-(diisopropylamino)ethyl methacrylate (DPA), displaying biomimetic and pH responsive properties, have been published, however these have been predominately polymersome based, whilst micelle systems have remained relatively unexplored. This study utilised nanoprecipitation to investigate the effects of solvent and buffer choice upon micelle size and polydispersity, and found using methanol produced monodisperse micelles of circa 70 nm diameter, whilst ethanol produced polydisperse systems with nanoparticles of circa 128 nm diameter. The choice of aqueous buffer, dialysis of the systems, extended storage, and exposure to a wide temperature range (5–70 °C) had no significant effect on micelle size, and the systems were highly resistant to dilution, indicating excellent colloidal stability. Optimisation of the nanoprecipitation process, post precipitation, was investigated, and model drugs successfully loaded whilst maintaining system stability. Subsequent in vitro studies suggested that the micelles were of negligible cellular toxicity, and an apparent cellular uptake was observed via confocal laser scanning microscopy. This paper presents the first report of an optimised nanoprecipitation methodology for the formation of MPC–DPA nanoparticle micelles, and in doing so achieved monodisperse systems with the size and physicochemical characteristics seen as desirable for long circulating therapeutic delivery vehicles.
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spelling pubmed-43593412015-03-18 Nanoprecipitation of polymeric nanoparticle micelles based on 2-methacryloyloxyethyl phosphorylcholine (MPC) with 2-(diisopropylamino)ethyl methacrylate (DPA), for intracellular delivery applications Salvage, Jonathan P. Thom, Christopher Lewis, Andrew L. Phillips, Gary J. Lloyd, Andrew W. J Mater Sci Mater Med Delivery Systems Biodistribution of nanoparticle-based intracellular delivery systems is mediated primarily by particle size and physicochemical properties. As such, overcoming the rapid removal of these by the reticuloendothelial system remains a significant challenge. To date, a number of copolymer nanoparticle systems based on 2-methacryloyloxyethyl phosphorylcholine (MPC) with 2-(diisopropylamino)ethyl methacrylate (DPA), displaying biomimetic and pH responsive properties, have been published, however these have been predominately polymersome based, whilst micelle systems have remained relatively unexplored. This study utilised nanoprecipitation to investigate the effects of solvent and buffer choice upon micelle size and polydispersity, and found using methanol produced monodisperse micelles of circa 70 nm diameter, whilst ethanol produced polydisperse systems with nanoparticles of circa 128 nm diameter. The choice of aqueous buffer, dialysis of the systems, extended storage, and exposure to a wide temperature range (5–70 °C) had no significant effect on micelle size, and the systems were highly resistant to dilution, indicating excellent colloidal stability. Optimisation of the nanoprecipitation process, post precipitation, was investigated, and model drugs successfully loaded whilst maintaining system stability. Subsequent in vitro studies suggested that the micelles were of negligible cellular toxicity, and an apparent cellular uptake was observed via confocal laser scanning microscopy. This paper presents the first report of an optimised nanoprecipitation methodology for the formation of MPC–DPA nanoparticle micelles, and in doing so achieved monodisperse systems with the size and physicochemical characteristics seen as desirable for long circulating therapeutic delivery vehicles. Springer US 2015-03-14 2015 /pmc/articles/PMC4359341/ /pubmed/25773229 http://dx.doi.org/10.1007/s10856-015-5480-9 Text en © The Author(s) 2015 https://creativecommons.org/licenses/by/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Delivery Systems
Salvage, Jonathan P.
Thom, Christopher
Lewis, Andrew L.
Phillips, Gary J.
Lloyd, Andrew W.
Nanoprecipitation of polymeric nanoparticle micelles based on 2-methacryloyloxyethyl phosphorylcholine (MPC) with 2-(diisopropylamino)ethyl methacrylate (DPA), for intracellular delivery applications
title Nanoprecipitation of polymeric nanoparticle micelles based on 2-methacryloyloxyethyl phosphorylcholine (MPC) with 2-(diisopropylamino)ethyl methacrylate (DPA), for intracellular delivery applications
title_full Nanoprecipitation of polymeric nanoparticle micelles based on 2-methacryloyloxyethyl phosphorylcholine (MPC) with 2-(diisopropylamino)ethyl methacrylate (DPA), for intracellular delivery applications
title_fullStr Nanoprecipitation of polymeric nanoparticle micelles based on 2-methacryloyloxyethyl phosphorylcholine (MPC) with 2-(diisopropylamino)ethyl methacrylate (DPA), for intracellular delivery applications
title_full_unstemmed Nanoprecipitation of polymeric nanoparticle micelles based on 2-methacryloyloxyethyl phosphorylcholine (MPC) with 2-(diisopropylamino)ethyl methacrylate (DPA), for intracellular delivery applications
title_short Nanoprecipitation of polymeric nanoparticle micelles based on 2-methacryloyloxyethyl phosphorylcholine (MPC) with 2-(diisopropylamino)ethyl methacrylate (DPA), for intracellular delivery applications
title_sort nanoprecipitation of polymeric nanoparticle micelles based on 2-methacryloyloxyethyl phosphorylcholine (mpc) with 2-(diisopropylamino)ethyl methacrylate (dpa), for intracellular delivery applications
topic Delivery Systems
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359341/
https://www.ncbi.nlm.nih.gov/pubmed/25773229
http://dx.doi.org/10.1007/s10856-015-5480-9
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