Functionalised dextran nanoparticles for drug delivery to the brain
Student thesis: Doctoral Thesis
Towards the development of drug carriers that are capable of crossing the Blood Brain Barrier, the techniques of emulsion polymerisation and nanoprecipitation have been utilised to produce nanoparticulate carriers from a systematic series of alkylglyceryl dextrans (of two different average molecular weights, 6 kDa and 100 kDa) that had been functionalised with ethyl and butyl cyanoacrylates. Also, zero length grafting of polylactic acid to butyl, octyl and hexadecylglyceryl dextrans has allowed the preparation of polylactic acid-functionalised nanoparticles. All materials and derived nanoparticles have been characterised by a combination of spectroscopic and analytical techniques. The average size of nanoparticles has been found to be in the range 100-500 nm. Tagging or loading of the nanoparticles with fluorophores or model drugs allowed the preliminary investigation of their capability to act as controlled-release devices. The effects of an esterase on the degradation of one such nanoparticulate carrier have been studied. Testing against bend3 cells revealed that all materials display dose-dependent cytotoxicity profiles, and allowed the selection of nanocarriers that may be potentially useful for further testing as therapeutic delivery vehicles for conditions of the brain.
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