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Studies on hydrophobic dendrimer nanoparticles

Rehal, Baljit Singh; (2006) Studies on hydrophobic dendrimer nanoparticles. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

It has been over a decade since evidence was adduced for the enhanced translocation of nanoparticles through Peyer's patches of the gut associated lymphoid tissue. In the search for a biodegradable drug carrier with enhanced translocation from the gut, dendrimers of 2-7nm diameter and lipidic exterior were studied. These lipophillic dendrimers, synthesised using Fmoc solid phase peptide techniques, were characterised using mass spectrometry, NMR, HPLC, molecular modelling and monolayer formation. The dendrimers proved to be poorly soluble or insoluble in aqueous media and the opportunity was taken to formulate the dendrimers as nanoparticles by precipitation from solution in dichloromethane. The effect of concentration and surfactant on the diameter and stability of dendrimer-derived nanoparticles formed from two short homologous series of dendrimers - one 5th generation and one 6th generation series and with surface C4, C10 or C12 groups - was investigated with photon correlation spectroscopy. Using pyrene (excitation 340nm) as a hydrophobic fluorescent probe, by measuring zeta potential and by studying the dendrimer at the air/water interface the packing of dendrimer-derived nanoparticles was assessed. Combined they made the basis for some calculations for the packing of dendrimer-derived nanoparticles. Calculations suggested a concentration and lipidic chain length dependent effect on packing density resulting in variable compact forms with hydrophobic interiors. The aggregates, derived from the 5th generation dendrimers with C10 or C12 surface lipidic chains, were studied in purified intestinal and stomach fluid, in which physical stability was assessed. Further aggregation of the dendrimer-aggregates occurs, more predominant in stomach fluid, because of an effect of pH and presence of salts, proteins and enzymes. Furthermore the dendrimer cytotoxicity was assessed in vitro using Caco-2 cells and red blood cells and made the foundation of the oral biodistribution study in animals using a radiolabelled dendrimer. The biodistribution was combined with histology to evaluate the uptake of the orally administered dendrimer. The study demonstrates that surface hydrophobicity, flexibility and concentration of the dendrimers, determines the size of the nanoparticles and their targeting to Peyer's patches and eventual translocation to the systemic circulation.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Studies on hydrophobic dendrimer nanoparticles
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Dendrimer; Hydrophobic; Nanoparticles
URI: https://discovery.ucl.ac.uk/id/eprint/10105145
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