ALA and m-ALA in bicontinuous lipid formulations: -Characterization and Transdermal Delivery

Licentiate thesis, 2004

δ-Aminolevulinic acid (ALA) and its methyl ester (m-ALA) are both used in photodynamic therapy (PDT) of certain non melanoma skin cancers as the basal cell carcinoma (BCC). In PDT the cancer cells are destroyed by a photochemical reaction that occurs when a photosensitive molecule is irradiated with light of a certain wavelength. The topically delivered ALA or m-ALA is, through the heme biosynthesis, transformed into the photosensitizer and accumulated in the chosen area. In this thesis ALA and m-ALA (as hydrochloride salts) were incorporated in the monoolein/propylene glycol/water (MO/PG/water) sponge phase. The addition of up to 16% of the methyl ester made the samples more or less anisotropic dependent on the amount added. Isotropic liquids were reformed when water was added and the samples were characterized with nuclear magnetic resonance diffusometry (NMRD) and small angle X-ray scattering (SAXS) in order to confirm the reformation of the bicontinuous sponge phase. Highly obstructed self-diffusion coefficients were found for every component, which is a clear signal of the presence of a bicontinuous structure such as the sponge phase. Moreover, the diffusion coefficients of MO were evidently slower than for the other components indicating that the lipid by itself constitutes the structural skeleton, the bilayer of the phase. Small angle X-ray scattering confirmed the presence of the sponge phase by the presence of diffuse Bragg peak in the diffractograms. The passive and iontophoretic transdermal delivery from sponge phases with added ALA and m-ALA were also studied. The sponge phase might have an optimal composition of the three components revealed from iontophoresis with 0.25% (w/w) ALA. The resulting fluxes from the two techniques with sponge phases incorporated with 16% m-ALA were comparable to fluxes received from clinically used formulations in both cases. Therefore, the MO/PG/water sponge phase can be regarded as a potential drug delivery vehicle for both passive diffusion and iontophoresis.