Jibry, Nadeen;
(2004)
Novel Amphiphilogels: Potential as Topical Drug and Vaccine Delivery Vehicles.
Doctoral thesis (Ph.D.), University College London.
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Abstract
Purpose: To characterise amphiphilogels (gels where both solid and liquid phases are amphiphilic and investigate their potential as topical drug and vaccine delivery vehicles. Methods: Amphiphilogels were prepared by mixing and heating the components (nonionic surfactants) at 60°C to form a clear isotropic sol phase; this was then cooled and set to a semisolid. The gels were characterised with respect to their microstructures, gelation temperatures (Tg), and flow properties. Some small hydrophobic drugs were incorporated into the gels, and the release of such drugs from the gels, through a semi- permeable membrane, measured in vitro with the use of diffusion cells. The permeation of a model protein into full-thickness pig skin in vitro using the diffusion cells was investigated; as was the immune responses elicited following topical application of this model protein antigen when formulated into the gels. In vivo skin irritation studies evaluated the irritation potential of the gels following single and repeated applications. Results: The gels are smooth, opaque, thermoreversible semisolids with a lifetime greater than two years. The microstructure consists of a 3-D network of interconnected gelator tubule clusters, or fibres, which immobilises the continuous phase. Within the tubular aggregates, the gelator molecules seem to be arranged in lamellae. Increasing gelator concentration results in a denser microstructural network, higher viscosity, and higher Tg. Three drugs were solubilised at concentrations up to 20% w/w in some amphiphilogeis. The drugs could also be incorporated into the gels by simply mixing the drug and gel; this method enabled a greater release rate of drugs from the gels. An aqueous phase (containing dissolved solute) could be incorporated within the more hydrophilic amphiphilogeis (to form water-in-gel systems) with little compromise to the gel stability. Hydrophilic molecules, e.g. proteins and vaccines, can thus be incorporated into the gels. The permeation of protein from water-in-gel systems into the epidermal layers of the skin was demonstrated in vitro. Immunisation studies showed no differences between the immune responses generated to a model antigen administered topically within the gels or when dissolved in aqueous solution. Skin irritation studies showed that the amphiphilogeis caused very little perturbation to the skin. Conclusions: This research indicates that the amphiphilogeis have the potential to be developed into topical drug delivery vehicles.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D. |
| Title: | Novel Amphiphilogels: Potential as Topical Drug and Vaccine Delivery Vehicles. |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis Digitised by Proquest. |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10122241 |
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