Preparation and in vitro evaluation of polylactic acid-mitomycin C microcapsules.
An emulsion method was developed for the incorporation of water-soluble mitomycin C into polylactic acid biodegradable microcapsules. With an average particle size of about 95 microns, microcapsules with a desired loading of from 3.65 to 13.80 per cent were prepared. These microcapsules, which contained both crystalline and finely dispersed drug particles, showed a dose-dependent drug release pattern with microcapsules of higher drug loading having a faster release rate than those of lower drug loading. Effective sterilization of the microcapsules for parenteral use was achieved by 60Co gamma-ray irradiation, which did not affect the microcapsule structure, release rate or drug stability. Mitomycin C showed dose-dependent antiproliferative activity against the growth of the K562 human erythroleukaemia cells. The microencapsulated dosage form of mitomycin C was found to enhance the drug's activity through sustained drug release. In experiments where drug concentrations in the cell medium were reduced according to the drug's biological half-life, the microcapsule systems showed a distinct advantage over the non-capsulated dose for the kinetic inhibition of K562 cell growth.
Tsai
D C
DC
School of Pharmacy, West Virginia University Medical Center, Morgantown 26506.
Howard
S A
SA
Hogan
T F
TF
Malanga
C J
CJ
Kandzari
S J
SJ
Ma
J K
JK
D000085:Acetates; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004339:Drug Compounding; D006801:Humans; D066298:In Vitro Techniques; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
D000085:Acetates; D008937:Mitomycins; D016685:Mitomycin