OBJECTIVE

Cyclic arginine-glycine-aspartic acid (RGD) peptide-anchored sterically stabilized albumin nanospheres (RGD-SN) have been investigated for the selective and preferential presentation of carrier contents at angiogenic endothelial cells overexpressing a(v) b(3) integrins on and around tumour tissue. Their targetability was assessed.

METHODS

Albumin nanospheres were formulated, conjugated with RGD/RAD peptide and characterized on the basis of size and size distribution. The control Arginine-Alanine-Aspartic acid (RAD) peptide-anchored sterically stabilized nanospheres (RAD-SN) and nanosphere with 5 mol% PEG (SN) without peptide conjugate were used for comparison with RGD-SN for in vitro cell binding, in vivo organ distribution and tumor angiogenesis studies.

RESULTS

The average size of all nanospheres prepared was approximately 100 nm and maximum drug entrapment was 67.2 ± 5.2%. In-vitro endothelial cell binding of nanospheres exhibited 8-fold higher binding of RGD-SN to human umbilical vein endothelial cells in comparison with the SN and RAD-SN. RGD peptide-anchored nanospheres were significantly (P ≤ 0.01) effective in the prevention of lung metastasis, angiogenesis and in effective regression of tumours compared with free fluorouracil, SN and RAD-SN. Results indicated that cyclic RGD peptide-anchored sterically stabilized nanospheres bearing fluorouracil were significantly (P ≤ 0.01) active against primary tumour and metastasis than the nontargeted sterically stabilized nanospheres and free drug.

CONCLUSIONS

Cyclic RGD peptide-anchored sterically stabilized nanospheres appears promising for targeted cancer chemotherapeutics.