In this study microgels have been used as novel drug carriers (i.e. a novel controlled drug delivery system) for either dermal or transdermal delivery. The experiments conducted in this project were, firstly, to investigate the uptake and release of model compounds with different physico-chemical properties (i.e. solubility and logKoct/w) to and from two colloidal gel systems. Secondly, the permeation of model compounds across a model skin membrane (silicone membrane), and human epidermis was investigated. The first part of the project was to co-synthesise temperature-sensitive colloidal microgels particles based on a co-polymer of poly(N-isopropylacrylamide) (90%)-co-butyl acrylate (10%) (NIPAM/BA) (90/10)(w/w)%, in the presence of and in the absence of ibuprofen (IBU), methyl paraben (MP), and propyl paraben (PP), by a surfactant-free emulsion polymerisation (SFEP) in water. Physico-chemical properties of the microgels were determined using different techniques including photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), nuclear magnetic resonance (NMR spectroscopy), and turbidimetric analysis (UV-vis). The uptake and release of the model compounds to and from colloidal microgel particles was controlled by the solubility and logKoct/w of the drugs. Their subsequent permeation across a model silicone membrane and human skin, were investigated over a range of temperatures (292 K – 313 K). The transport rate of IBU and, PP from poly(NIPAM) microgel is significantly reduced by two and one order of magnitude, respectively, compared with the transport rate of saturated solutions. A huge reduction in the flux indicates that the microgel retards permeation of the drug across both membranes, and hence the microgel can be considered as a permeation retarder. However, fluxes of MP from poly(NIPAM) microgel are equivalents to fluxes of saturated solutions of MP. There is a clear correlation between the solubility and logKoct/w value of the drugs and the flux value for the microgels, incorporating the drugs, across both types of membranes. In the second part of the work, a co-polymer of poly(NIPAM) (85%) co-butyl acrylate (10%) co-methacrylic acid (5%) (NIPAM/BA/MAA) (85/10/5) microgel was synthesised and investigated as a potential pH and temperature sensitive transdermal delivery device. Three compounds having different logKoct/w and solubilities were incorporated into the microgel, namely: salicylamide (SA), methyl paraben and propyl paraben.
Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:549220 |
Date | January 2005 |
Creators | Castro-Lopez, Vanessa |
Publisher | University of Greenwich |
Source Sets | Ethos UK |
Detected Language | English |
Type | Electronic Thesis or Dissertation |
Source | http://gala.gre.ac.uk/6230/ |
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