Abstract
Many drugs have poor aqueous solubility which causes problems for their formulation as effective medicines. One way of solving this problem involves solubilizing drugs using aqueous dispersions of self-assembled surfactant micelles. It is well-established that surfactant micelles can solubilize drug, but where the drug will locate within the micelles and the factors that affect this are not fully understood. It is the locus of drug solubilization, however, that is thought to be important in determining the loading-capacity of the micelles, and it is this too that affects the drug’s stability and its rate of release inside the body and so it also impacts the drug’s therapeutic activity.In order to gain a better understanding of the location of drug in surfactant micelles, a series of systematic studies have been performed to determine the extent and locus of solubilization of two poorly water-soluble steroids, 4-cholesten-3-one (4-CHOL) and adrenosterone (ADRENO) compounds in a range of C12-chain surfactant of varying head group.
The solubilisation capacities of steroids in the various surfactant micelle, as well as the interfacial and solvation behaviour of the various surfactant systems were explored. In order to estimate the preferred site(s) of solubilization of the steroids within the micelles, neutron techniques (both small-angle neutron scattering (SANS) and specular neutron reflectivity (SNR)) in combination with isotopic (H/D) contrast variation were used. The NR study revealed that regardless of the nature of the head groups, steroids were solubilised within the hydrophobic chain of surfactant at the air-water interface. The SANS studies were in good agreement with the NR study, and also suggested in some cases the presence of steroids could change the shape of the micelle.
The information gained in these studies has provided for a more complete understanding of the relationship between the structure of a surfactant and the structure of the micelles likely to be formed when loaded with steroid drugs, allowing predictions to be made to guide the design of new surfactants to optimize steroid drug loading.
| Date of Award | 2019 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | David Barlow (Supervisor) & Margaret Lawrence (Supervisor) |