Preparation and characterization of a biodegradable drug targeting system for anticancer drug delivery: microsphere-antibody conjugate.
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?microm. 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 (approximately 22-46% released in 24 h depending on the amount of GTA used) were much slower compared to 5-FU (approximately 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 approximately 54-70% and approximately 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 approximately 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).
Muvaffak
Asli
A
Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. amuvaffa@bidmc.harvard.edu
Gurhan
Ismet
I
Gunduz
Ufuk
U
Hasirci
Nesrin
N
D000906:Antibodies / Q000737:chemistry; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents; D016503:Drug Delivery Systems; D004355:Drug Stability; D005079:Excipients; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics; D005780:Gelatin; D005976:Glutaral / Q000737:chemistry; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008863:Microspheres; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000737:chemistry
D000906:Antibodies; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D005079:Excipients; D005456:Fluorescent Dyes; D012710:Serum Albumin, Bovine; D005780:Gelatin; D016650:Fluorescein-5-isothiocyanate; D005976:Glutaral; D005472:Fluorouracil; D008727:Methotrexate