Co-nanoprecipitation: preparation of sterically stabilised polymer nanoparticles for drug delivery applications

Ford, Jane
(2015) Co-nanoprecipitation: preparation of sterically stabilised polymer nanoparticles for drug delivery applications. Doctor of Philosophy thesis, University of Liverpool.

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Co-nanoprecipitation: Preparation of Sterically Stabilised Nanoparticles for Drug Delivery Applications The co-nanoprecipitation of linear amphiphilic A-B block copolymers and branched hydrophobic co/terpolymers has been used for the first time to generate uniform, salt stable dispersions of aqueous polymer nanoparticles. The nanoprecipitation of the branched polymers was studied in the absence of A-B block copolymers and the conditions chosen for further co-nanoprecipitation studies were chosen on the ability to ensure the mixed solvent system immediately after good solvent addition would guarantee nanoparticle formation. Variation of the ratio of the two polymer architectures using this simple technique has led to varying z-average diameters, narrow polydispersity particle distributions and tuneable stability to salt addition and storage within aqueous salt conditions. Polarity studies provided further evidence that during addition of increasing amounts of A-B block copolymer, the hydrophobicity of the internal core was maintained and only slight deviations were observed suggesting the PEG chains were located on the nanoparticle surface. Multiple nanoprecipitations were also shown to be possible through direct addition of polymer solutions to aqueous nanoparticle dispersions after solvent removal, leading to particle concentration increase without modification of the initial nanoprecipitate size. The dye molecule fluoresceinamine was selected as a model guest molecule for encapsulation during co-nanoprecipitation (10 wt %). Nanoparticles which were stable under physiologically relevant conditions were generated and studied for their cytotoxicity and transcellular permeability using Caco-2 cells. These materials showed low toxicity at the concentrations studied and enhanced permeation though the Caco-2 cell monolayer, which is a model of the intestinal epithelial cells. A nanomaterial was taken forward for accumulation studies and transcellular permeability in the presence of endocytic inhibitors, suggesting uptake proceeded via an active mechanism. Excellent drug loading potentials were observed during co-nanoprecipitation experiments with HIV anti-retrovirals, and up to 25 wt % of efavirenz and ritonavir and 20 wt % lopinavir were encapsulated. As well as anti-retrovirals, encapsulation of an anti-cancer drug molecule SN-38 was studied and colloidally stable nanoparticles with narrow polydispersity particle distributions were obtained. In vitro cytotoxicity testing of the materials showed a comparable toxicity to that of SN-38. Multiple nanoprecipitations including SN-38 were successful and an increased concentration of SN-38 was achieved, whilst maintaining the same volume of anti-solvent. Overall, the co-nanoprecipitation approach has provided a fast and efficient route to sterically stabilised nanoparticles without the need for additional surfactants or filtration. Particles can be loaded with various drug molecules and pharmacological benefits were observed for some materials, suggesting future use for drug delivery applications.

Item Type: Thesis (Doctor of Philosophy)
Subjects: Q Science > QD Chemistry
Divisions: Fac of Science & Engineering > School of Chemistry
Depositing User: Symplectic Admin
Date Deposited: 07 Sep 2016 10:26
Last Modified: 01 Aug 2018 01:30
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