A vanadium/aspirin complex controlled release using a poly(beta-propiolactone) film. Effects on osteosarcoma cells.
A delivery system for vanadium was developed using poly(beta-propiolactone) (PbetaPL) films. The release kinetics of a complex of vanadium (IV) with aspirin (VOAspi) was evaluated with films prepared from polymers of different molecular weights, as well as with variable drug load. A sustained release of vanadium over 7 days was achieved. The drug release kinetics depends on contributions from two factors: (a) diffusion of the drug; and (b) erosion of the PbetaPL film. The experimental data at an early stage of release were fitted with a diffusion model, which allowed determination of the diffusion coefficient of the drug. VOAspi does not show strong interaction with the polymer, as demonstrated by the low apparent partition coefficient (approximately 10(-2)). UMR106 osteosarcoma cells were used as a model to evaluate the anticarcinogenic effects of the VOAspi released from the PbetaPPL film. VOAspi-PbetaPL film inhibited cell proliferation in a dose-response manner and induced formation of approximately half of the thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation. compared to that with free VOAspi in solution. The unloaded PbetaPL film did not generate cytotoxicity, as evaluated by cell growth and TBARS. Thus, the polymer-embedded VOAspi retained the antiproliferative effects showing lower cytotoxicity than the free drug. Results with VOAspi-PbetaPL films suggest that this delivery system may have promising biomedical and therapeutic applications.
Cortizo
M S
MS
INIFTA, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Argentina. cortizo@biol.unlp.edu.ar
Alessandrini
J L
JL
Etcheverr
S B
SB
Cortizo
A M
AM
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001859:Bone Neoplasms / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D004338:Drug Combinations; D016503:Drug Delivery Systems; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D010006:Osteoblasts / Q000187:drug effects; D012516:Osteosarcoma / Q000188:drug therapy; D018384:Oxidative Stress / Q000187:drug effects; D011420:Propiolactone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014639:Vanadium / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014867:Water
D004338:Drug Combinations; D017392:Thiobarbituric Acid Reactive Substances; D014639:Vanadium; D014867:Water; D011420:Propiolactone; D001241:Aspirin