Interaction of mTHPC liposomal formulations with serum proteins
Résumé
The use of liposomes as drug delivery systems is an accepted approach to improve the photosensitizer efficacy. Because of their characteristic small size (between 50 and 200 nm) and good solubility and stability, liposomes represent an ideal delivery system for nonpolar photodrugs. In this perspective, a clinically approved photosensitizer, meta-tetra(hydroxyphenyl)chlorin (mTHPC) has been loaded into liposomes with or without addition of PEGylated lipid. The present study addresses the distribution pattern of liposomal mTHPC (Foslip(R) and Fospeg(R)) in blood serum assessed by gel-filtration chromatography It was found that the affinity of pure and liposome-based mTHPC towards different plasma proteins is almost identical. The major part of the photosensitizer localizes in the high density lipoproteins fractions, while a minor fraction passes through the column with low-density lipoproteins. Only a small part of mTHPC molecules is found in the albumin fraction. As opposed to conventional liposomes with a very rapid disruption of the lipid vesicles and fast release of the drugs, mTHPC loaded DPPC/DPPG liposomes show a very slow release of the active component. After 30 min of Foslip(R) incubation with serum only a small percentage of mTHPC redistributes from the liposomes. Increasing incubation time to 6 h results in a significant reduction of the mTHPC fluorescence signal associated with mTHPC embedded into liposomes and concomitant increase of the signal associated with the protein- based bands. After 24 h incubation the distribution pattern was similar to the elution profile of serum containing free mTHPC. In contrast to Foslip(R), short incubation of PEGylated liposomes containing mTHPC (Fospeg(R)) with serum results in a release of approximately half of mTHPC from the lipid carriers. The kinetics of release is clearly two-phased: rapid release followed by slow redistribution. The slow phase is decelerated compared to Foslip(R).