Effect of oil-in-water emulsions on 5-aminolevulinic acid uptake and metabolism to PpIX in cultured MCF-7 cells.
OBJECTIVE
To identify the optimal vehicle for fast and efficient cellular production of the photosensitizer, protoporphyrin IX (PpIX), upon administration of 5-aminolevulinic acid (ALA).


METHODS
ALA in various oil/water o/w emulsions was applied to the human mammary epithelial cell line (MCF-7) cultured in microplates. Upon incubation for 14 h, the accumulated amount of PpIX was determined by fluorescence spectroscopy. Variables such as the pH and concentration of the emulsions, the temperature and duration of incubation were examined along with the importance of ALA concentration and the presence of endocytosis inhibitors.


RESULTS
An increase in the amount of produced PpIX was observed with an increase in extracellular pH, incubation temperature, and ALA concentration. A saturable mechanism of PpIX accumulation was evident, mainly as a result of the uptake mechanism for ALA. Some of the o/w emulsions increased the amount of intracellular PpIX, and the results indicated that this was not due to an increased k(m) of the extracellular ALA to intracellular PpIX conversion, but to the increased endocytotic uptake in the presence of the emulsions. In general, the increase in PpIX in the presence of emulsions relative to the control was more pronounced after 1 h as compared to after 2-4 h.


CONCLUSIONS
The formation of PpIX in MCF-7 cells exposed to ALA is improved by the presence of certain o/w emulsions, which could be explained by endocytosis.
Nielsen
Hanne Mørck
HM
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zürich (ETH Zürich), Winterthurerstrasse 190, 8057 Zürich, Switzerland. hmn@dfuni.dk
Aemisegger
Caroline
C
Burmeister
Gerd
G
Schuchter
Ursula
U
Gander
Bruno
B
D000622:Aminolevulinic Acid / Q000737:chemistry* / Q000378:metabolism*; D004655:Emulsions; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D009821:Oils / Q000737:chemistry / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014867:Water / Q000737:chemistry / Q000378:metabolism
D004655:Emulsions; D009821:Oils; D011524:Protoporphyrins; D014867:Water; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX