Transport and localisation of m-THPC in vitro.
The hydrophobic photosensitising agent meta-tetrahydroxyphenylchlorin (m-THPC) must be formulated with an appropriate vehicle before administration. Studies were carried out with murine leukaemia cells in vitro to assess the role of formulation in drug pharmacokinetics. The rate-limiting step in m-THPC accumulation was the slow conversion of drug aggregates to monomers upon dilution into growth media. Only non-viable cells with damaged membranes showed a rapid drug uptake, otherwise m-THPC accumulation was a slow process. It was found that m-THPC was localised mainly at mitochondrial loci. Subsequent irradiation resulted in the release of cytochrome c into the cytosol, triggering a rapid activation of caspase-3, which led to an apoptotic response. Plasma distribution of m-THPC involved binding to lipoprotein species, with only a slight appearance of the drug in the albumin fraction.
Kessel
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Department of Pharmacology, Wayne State University, Detroit, Michigan, USA.
D000818:Animals; D001692:Biological Transport; D002470:Cell Survival; D004337:Drug Carriers; D008652:Mesoporphyrins / Q000493:pharmacokinetics*; D051379:Mice; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*
D004337:Drug Carriers; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin