Heat-stabilized albumin microspheres as a sustained drug delivery system for the antimetabolite, 5-fluorouracil.
The aim of this investigation was to study the release behaviour of heat-stabilized albumin microspheres with entrapped 5-Fluorouracil (5-FU) in vitro, and determine the organ distribution in vivo, for potential application in the treatment of ovarian cancer. Additionally, blood chemistry and haematological profiles were composed after intraperitoneal administration of 5-FU-loaded albumin microspheres into adult female Wistar rats. Microspheres with entrapped 5-FU was also added to 10(4) HeLa cells, cultured in Eagles Minimum Essential Medium, and the effects of drug leakage studied. It was found that cell division of the cells was halted before one cell cycle, as demonstrated by the absence of micronuclei and double nuclei. Blood chemistry and haematology indicated mild systemic toxic effects of the drug e.g. bone marrow suppression and liver involvement, reaching a maximum by Day 12 after intraperitoneal administration of 5-FU-microspheres. A return to normal however was observed within 4 weeks. The data suggest that 5-FU-loaded albumin microspheres may be beneficial in reducing the severe side-effects of this antimetabolite, whilst still maintaining therapeutic levels to cause tumour cell death.
Drug Delivery Systems Research Unit, School of Life Sciences, Cape Town, Republic of South Africa.
E J
EJ
Truter
D000418:Albumins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002455:Cell Division / Q000187:drug effects; D016503:Drug Delivery Systems; D004906:Erythrocyte Count; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D006358:Hot Temperature; D007274:Injections, Intraperitoneal; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008863:Microspheres; D010949:Plasma / Q000378:metabolism; D010976:Platelet Count; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D005723:gamma-Glutamyltransferase / Q000097:blood
D000418:Albumins; D000963:Antimetabolites; D006454:Hemoglobins; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D005472:Fluorouracil