Chemo-embolization of experimental liver metastases. Part I: distribution of biodegradable microspheres of different sizes in an animal model for the locoregional therapy.
An experimental in vivo rat model was established to simulate the embolization therapy of non-resectable liver metastases with microparticulate systems. The effects of biodegradable microspheres on a transplanted liver-tumor cell line in rat livers were investigated with respect to particle size. The distribution of fluorescence-labelled microspheres was investigated to characterize the effects of long-term embolization with biodegradable microspheres, and the suitability and relevance of this animal model. Novikoff hepatoma cells were implanted into the central liver lobe of Sprague-Dawley rats. After seven days, four batches of fluorescence-marked microspheres (17 microm, 25 microm, 30 microm, and 40 microm) were administered into the proper hepatic artery. Liver(including the tumor), lung and spleen were isolated and frozen sections and tissue cubes of liver-, border-, and tumor tissue were prepared. The sections were examined by fluorescence microscopy. The cubes were extracted and the fluorescence of the marker quantified. During operation, microspheres smaller than 40 microm did not cause complete embolization. The slides showed the spreading of the smaller particles to the spleen and lung. Only 40 microm particles accumulated in the liver and were rarely detectable in other organs. The extraction showed a high concentration of the 40 microm particles in the border tissue. Apparently they were trapped proximal to the tumor capillary system and therefore showed a high ratio of border/tumor concentration. Microparticles smaller than 40 microm had a border/tumor concentration ratio of less than one and were distributed to the spleen and lung. In conclusion, a mean particle diameter of at least 40 microm is required for embolization. Thus, the model shows similarity to clinical situations in the treatment of human liver tumor and metastases.
Bastian
P
P
Department of Pharmaceutics and Biopharmacy, Philipps-University, Marburg, Germany.
Bartkowski
R
R
Köhler
H
H
Kissel
T
T
D000818:Animals; D001672:Biocompatible Materials / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods; D004195:Disease Models, Animal; D004621:Embolization, Therapeutic / Q000379:methods*; D005260:Female; D005453:Fluorescence; D019344:Lactic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000556:secondary* / Q000628:therapy*; D008856:Microscopy, Fluorescence; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D001672:Biocompatible Materials; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid