Studies on cationic hydrophobic dendrons and hydrophilic dendrimers

A group of cationic amphiphilic polylysine dendrons and dendrimers of various geometries and lipophilicity were synthesised and characterised to investigate their potential uses in drug delivery.;Engineering dendrimers and dendrons (partial dendrimers) is by controlling their generation number, number of branching units and surface functionalities. Dendrons of the appropriate hydrophile-lipophile balance (HLB), size and topology can self- assemble into higher order structures, broadening their potential for use as drug and gene carriers. Novel supramolecular vesicular structures comprised of a cationic lipidic dendron were developed and named "dendrisomes". Dendrisomes were tested for their potential as drug delivery carriers for benzyl penicillin (penicillin G), used as a model of a negatively charged water soluble drug. Their interaction with cholesterol was also studied using techniques such as photon correlation spectroscopy, transmission electron microscopy and differential scanning calorimetry. The gradual transformation of dendrisomes into isotropic surfactant/dendron mixed micelles was achieved via the interaction with the nonionic surfactant, Triton X-100.Thestoichiometry of the dendron-surfactant interaction was determined.;Heparin is a negatively charged polysaccharide which is known for its anticoagulant activity, pro-angiogenic character and poor oral absorption. A hydrophilic dendrimer with 64 amino groups was complexed with heparin via electrostatic interactions to form heparin dendriplexes. An effect on heparin anticoagulant activity, angiogenic properties as well as its absorption profile is anticipated upon complexation, depending on the physicochemical properties and stability of the dendriplexes in vitro and in vivo. The modulation of heparin anticoagulant activity in vitro and in vivo was studied: complete association occurs at 1:1 mass ratio at which ratio the anticoagulant activity of heparin is abolished. A change in heparin pharmacodynamic and pharmacokinetic properties occurred when complexed with the dendrimer, demonstrated by uptake measurements across Caco-2 monolayers and biodistribution (in rats) of [3H] labelled dendrimer, [3H] labelled heparin and the dendriplexes. However, the use of dendrimers as an approach to enhance heparin absorption in vitro and in vivo was not much successful due to the low uptake enhancement ratio and heparin deactivation.;It is concluded that dendrimers and dendrons are potential tools in drug delivery as discrete nanodevices (uni-micellar dendrimers), supramolecular assemblies (dendrisomes) and active moieties themselves (as heparin antidote and in angiogenesis therapy).;An interesting intrinsic fluorescence was discovered in these molecules without a fluorophore, a property which can be used as a tool in their visualisation and quantification of cellular uptake. The complexation between dendrimers and a small dye molecule carboxyfluorescein was also studied to prove the ability of the dendrimer to act as nanocarrier devices.