Development and characterization of 5-FU bearing ferritin appended solid lipid nanoparticles for tumour targeting.
Ferritin coupled solid lipid nanoparticles were investigated for tumour targeting. Solid lipid nanoparticles were prepared using HSPC, cholesterol, DSPE and triolien. The SLNs without ferritin which has similar lipid composition were used for comparison. SLNs preparations were characterized for shape, size and percentage entrapment. The average size of SLNs was found to be in the range 110-152 nm and maximum drug entrapment was found to be 34.6-39.1%. In vitro drug release from the formulations is obeying fickian release kinetics. Cellular uptake and IC50 values of the formulation were determined in vitro in MDA-MB-468 breast cancer cells. In vitro cell binding of Fr-SLN exhibits 7.7-folds higher binding to MDA-MB-468 breast cancer cells in comparison to plain SLNs. Ex-vivo cytotoxicity assay on targeted nanoparticles gave IC50 of 1.28 microM and non-targeted nanoparticles gave IC50 of 3.56 microM. In therapeutic experiments, 5-FU, SLNs and Fr-SLNs were administered at the dose of 10 mg 5-FU/kg body weight to MDA-MB-468 tumour bearing Balb/c mice. Administration of Fr-SLNs formulation results in effective reduction in tumour growth as compared with free 5-FU and plain SLNs. The result demonstrates that this delivery system possessed an enhanced anti-tumour activity. The results warrant further evaluation of this delivery system.
Jain
Sanjay K
SK
Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar, India. drskjainsagar@rediffmail.com
Chaurasiya
Akash
A
Gupta
Yashwant
Y
Jain
Anekant
A
Dagur
Pradeep
P
Joshi
Beenu
B
Katoch
Vishwa M
VM
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems; D005293:Ferritins / Q000008:administration & dosage*; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D020128:Inhibitory Concentration 50; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D008055:Lipids; D005293:Ferritins; D005472:Fluorouracil