Redistribution of meta-tetra(hydroxyphenyl)chlorin (m-THPC) from conventional and PEGylated liposomes to biological substrates

Abstract

We used the phenomenon of previously described photoinduced fluorescence quenching and fluorescence polarization to evaluate the transfer of meta-tetra(hydroxyphenyl)chlorin (m-THPC) from commercial high-drug load liposomes to plasma proteins and model membranes. Fluorescence quenching of m-THPC in liposomes by iodide indicates that part of m-THPC in PEGylated liposomes is localized in the PEG shell, while the rest is bound to the lipid bilayer. It was shown that the two molecule pools in the commercial PEGylated liposomal formulation Fospeg® condition the characteristics of the m-THPC release kinetics. A substantial percentage of m-THPC from Fospeg® is released much faster than from the conventional liposomal formulation Foslip®. Using the technique of resonance light scattering, it was shown that partial m-THPC aggregation is present in liposomes with very high drug loads, higher in PEGylated liposomes compared to conventional ones.

Photodynamic therapy with conventional and PEGylated liposomal formulations of mTHPC (temoporfin): comparison of treatment efficacy and distribution characteristics in vivo

“…The release rate of the liposome-encapsulated drug in circulation is an essential parameter affecting the pharmacokinetics and therapeutic efficacy of the formulation. 15,27 Although in vitro liposomal mTHPC release to serum proteins has been reported, 17 this characteristic was not studied in vivo in sufficient detail. The results of the pharmacokinetic study by Decker et al 14 suggested that a fraction of mTHPC is released from liposomes prior to elimination from the blood stream, as deduced from the ratio of rate constants of mTHPC elimination from the blood stream within the lipid formulation and after transfer from the liposomes to the blood components.…”

“…The amplitude of the effect is significantly dependent on the mTHPC concentration in liposomes. 17 As described, 17 the amplitude of photoinduced fluorescence quenching in the plasma samples allows the local mTHPC concentration in liposomes to be determined using a method described in Table S1. These data are used to calculate the percentage of the drug released from intact liposomes at a given time after injection when compared to the initial drug formulation (Foslip ® or Fospeg ® ).…”

mTHPC – A drug on its way from second to third generation photosensitizer?

“…A fluorescence quenching study of Fospeg showed two molecular pools; one in the PEG shell and one in the lipid bilayer. The different release kinetics account in part for the faster release of mTHPC from Fospeg compared to Foslip [19] and for the increased bioavailability of mTHPC from liposomal preparations [20]. In the context of new applications, a study investigated the antimicrobial effect of liposome enriched mTHPC for the use of Foscan in periodontal diseases.…”

Current Developments in Using MESO-(TETRA) Substituted Porphyrins for PDT

“…For example, encapsulating mTHPC into nontoxic liposomes (Foslip ® ) or modified pegylated liposomes (Fospeg ® ) yields carriers of high capacity for the otherwise poorly water-soluble drugs. 19,20 Additional benefits are different drug release times, 21 different selectivities for tissue and cell types and more rapid tissue clearance, 22 Current developments in using meso-(Tetra)substituted porphyrins for PDT 7 improved pharmacokinetics and lower drug and light doses. 23,24,25 We have recently reviewed the state-of-the-art for mTHPC and its development and the reader is referred to these articles for more details on chemical and biological studies of Temoporfin.…”

“…Current developments in using meso-(Tetra)substituted porphyrins for PDT 21 4 μM concentration. Initial work carried out on the pre-incubation of cells in glycosylated albumin showed a 40-45% inhibition of uptake of TPP(p-Deg-O-β-GalOH) 3 and TPP(p-Deg-O-α-ManOH) 3 indicating a cell-sugar-receptor saturation.…”