RGD modified albumin nanospheres for tumour vasculature targeting.

Abstract

OBJECTIVES:

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.

KEY FINDINGS:

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.

• Authors: Praveen K Dubey, Deepak Singodia, Rahul K Verma, Suresh P Vyas
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 63 Issue 1 Pg. 33-40 (Jan 2011) ISSN: 2042-7158 [Electronic] England
• PMID: 21155813 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society.

Chemical References

• Antimetabolites, Antineoplastic
• Drug Carriers
• Integrin alphaVbeta3
• Peptides, Cyclic
• cyclic arginine-glycine-aspartic acid peptide
• Serum Albumin, Bovine
• Polyethylene Glycols
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (administration & dosage, pharmacokinetics, pharmacology)
• Cattle
• Cells, Cultured
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Endothelial Cells (drug effects, metabolism)
• Fluorouracil (administration & dosage, pharmacokinetics, pharmacology)
• Humans
• Integrin alphaVbeta3 (metabolism)
• Male
• Melanoma, Experimental (blood supply, drug therapy, pathology)
• Mice
• Mice, Inbred BALB C
• Nanospheres
• Neoplasm Metastasis (prevention & control)
• Neovascularization, Pathologic (drug therapy)
• Particle Size
• Peptides, Cyclic (chemistry)
• Polyethylene Glycols (chemistry)
• Serum Albumin, Bovine (chemistry)
• Tissue Distribution
• Umbilical Veins (drug effects, metabolism)