Solid tumor chemotherapy and in vivo distribution of fluorouracil following administration in poly(L-lactic acid) microspheres.
The physicochemical properties and in vivo distribution of poly(L-lactide) (L-PLA) microspheres containing 5-fluorouracil (5-FU) prepared by a solvent evaporation method were evaluated for potential use in the treatment of liver cancers. Two different molecular weight polymers of L-PLA [L-PLA1 (152,500 Da) and L-PLA2 (52,000 Da)] were used to prepare 5-FU-loaded microspheres. The mean particle size of the microspheres was 3-6 microns, and there was a direct relationship between the mean particle size and the molecular weight of the polymers. The drug release behavior from microspheres exhibited a diffusion mechanism in different dissolution media, with the molecular weight of the polymer being a major factor in controlling the drug release and degradation rates. Following intravenous injection of 99mTc-labeled L-PLA microspheres, with or without 5-FU, or free 5-FU into mice, L-PLA2 microspheres localized mainly in the liver. The disappearance rate of radioactivity from the tissue was very slow in comparison to that of free 5-FU. The results were confirmed by histological examination of liver tissue following administration of fluorescein particles. In addition, growth of a human liver tumor as first transplant generation under the renal capsule of immunocompetent rats and antitumor activity of L-PLA2 microspheres were investigated. Histological examination by optical microscopy showed that there was no neoplastic tissue of the kidney or in other tissues examined after treatment.
Ciftci
K
K
Faculty of Pharmacy, Department of Pharmaceutical Technology, University of Hacettepe, Ankara, Turkey.
Hincal
A A
AA
Kas
H S
HS
Ercan
T M
TM
Sungur
A
A
Guven
O
O
Ruacan
S
S
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001673:Biodegradation, Environmental; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D019344:Lactic Acid; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy; D008863:Microspheres; D008970:Molecular Weight; D010316:Particle Size; D011091:Polyesters; D011108:Polymers; D051381:Rats; D017208:Rats, Wistar; D013667:Technetium; D014018:Tissue Distribution; D014783:Viscosity
D000964:Antimetabolites, Antineoplastic; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D013667:Technetium; D005472:Fluorouracil