Preparation and characterization of a biodegradable drug targeting system for anticancer drug delivery: Microsphere-antibody conjugate

Muvaffak A., Gurhan I., Gunduz U., Hasirci N.

JOURNAL OF DRUG TARGETING, vol.13, no.3, pp.151-159, 2005 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 13 Issue: 3
  • Publication Date: 2005
  • Doi Number: 10.1080/10611860400029069
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.151-159
  • Keywords: gelatin microspheres-anti-BSA conjugate, drug targeting, cytotoxicity, immunofluorescence, CROSS-LINKED GELATIN, STARCH MICROPARTICLES, CANCER, 5-FLUOROURACIL, INTERLEUKIN-2, CHEMOTHERAPY, PROTEINS, RELEASE, MUCOSA, AGENTS
  • Middle East Technical University Affiliated: Yes


Targeted delivery of anticancer drugs is one of the most actively pursued goals in anticancer chemotherapy. A major disadvantage of anticancer drugs is their lack of selectivity for tumour tissue, which causes severe side effects and results in low cure rates. Any strategy by which a cytotoxic drug is targeted to the tumour, thus increasing the therapeutic index of the drug, is a way of improving cancer chemotherapy and minimizing systematic toxicity. This study covers the preparation of the gelatin microsphere (GM)-anti-bovine serum albumin (anti-BSA) conjugate for the development of a drug targeting approach for anticancer drug delivery. Microspheres of 5% (w/v) gelatin content were prepared by crosslinking with glutaraldehyde (GTA) at 0.05 and 0.50% (v/v) concentration. Microspheres were in the size range of 71-141 mu m. The suitability of these microspheres as drug carriers for anticancer drug delivery was investigated in vitro by studying the release profiles of loaded methotrexate (MTX) and 5-fluorouracil (5-FU) and the cytotoxicities on cancer cell lines. The in vitro MTX release profiles (similar to 22-46% released in 24 h depending on the amount of GTA used) were much slower compared to 5-FU (similar to 42-91% released in 24 h). Both drugs demonstrated an initial fast release, which was followed by gradual, sustained drug release. The MTT cytotoxicity test results of GMs loaded with 5-FU and MTX showed similar to 54-70% and similar to 52-67% cytotoxicities in 4 days. In general, incorporation of MTX and 5-FU in microspheres enhanced the cytotoxic effect in a more prolonged manner compared to the free drugs. Gelatin micospheres were chemically conjugated to anti-BSA and the antigen-antibody activities were studied by immunofluorescence. Results indicated similar to 80% binding with conjugated anti-BSA and BSA-FITC. Based on their low cytotoxicity and the high antigen binding efficiencies, anti-BSA conjugated gelatin microspheres could be suitable targeted drug carrier systems for selective and long-term delivery of anticancer drugs to a specific body compartment (i.e. bladder cancer).