Biodistribution of meta-tetra(hydroxyphenyl)chlorin incorporated into surface-modified nanocapsules in tumor-bearing mice.
meta-Tetra(hydroxyphenyl)chlorin (mTHPC), a second generation photosensitizer used in photodynamic therapy (PDT), was incorporated into long circulating carriers with the aim of improving the tumor selectivity by limiting the reticuloendothelial system (RES) uptake. Biodistribution of mTHPC (0.06 mg kg(-1) was studied directly in nude mice bearing HT29 human tumor by optical fiber fluorimetry and tissue drug contents were determined by HPLC after extraction. The drug was incorporated in the oily core of nanocapsules surrounded by poly(D,L lactic acid) (PLA NCs), PLA grafted with polyethylene glycol (PLA-PEG) or PLA coated with poloxamer 188 (polox PLA). Compared to PLA NCs, incorporation of mTHPC in surface-modified nanocapsules resulted in strong modifications of the drug biodistribution and tumoral retention with a three-fold increase of drug level as early as 24 h post-administration. A reduced liver uptake was observed at early times post-administration indicating that surface-modified NCs are effective in limiting the RES uptake and could be potential carriers to enhance the therapeutic ratio of lipophilic photosensitizers. Furthermore, in situ fluorescence measurements and concentration data were found in broad agreement showing that optical fiber fluorimetry is a very sensitive method that can be used to follow the biodistribution of fluorescent drugs in real-time.
Bourdon
O
O
LPBC UMR CNRS 7033 and Université Pierre et Marie Curie L.P.B.C., Université P. et M. Curie, 4 place Jussieu, case 138, 75252 Paris 05, France.
Laville
I
I
Carrez
D
D
Croisy
A
A
Fedel
Ph
P
Kasselouri
A
A
Prognon
P
P
Legrand
P
P
Blais
J
J
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008652:Mesoporphyrins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012867:Skin / Q000378:metabolism*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D008652:Mesoporphyrins; D011838:Radiation-Sensitizing Agents; C072269:temoporfin