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Integrin receptor‐selective peptide based targeting reduces immunogenicity and improves vascular delivery of streptokinase
Author(s) -
DUBEY NIDHI,
Agrawal Abhinav,
Thakur Abhilasha,
Agrawal G.P.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1089.2
Subject(s) - liposome , immunogenicity , chemistry , in vivo , drug delivery , integrin , peptide , ex vivo , pharmacology , penetration (warfare) , biophysics , in vitro , receptor , immunology , immune system , medicine , biochemistry , biology , microbiology and biotechnology , organic chemistry , operations research , engineering
Streptokinase (STK) is used in treating thrombosis; however, immunogenicity and uniform distribution in the body with resulting bleeding complications are major limiting factors. We hypothesized that an integrin‐receptor‐selective peptide based delivery system would reduce immunogenicity and improve vascular delivery of STK. Plain and surface modified ligand anchored liposomes were prepared using reverse phase evaporation method. These were characterized for shape, size, polydispersity index, entrapment efficiency, number of vesicles/mm 3 and in vitro drug release. Liposomal surface was modified by attaching RGD peptide as ligand. Modified liposomes exhibited lower entrapment efficiency (17.7 ± 0.3% vs 20.1 ± 0.2% for conventional liposomes) and released more drug in 48 hours (79.8 ± 2.1%) as compared to conventional liposomes (67.8 ± 3.7%). In ex‐vivo clot penetration studies using fluorescence imaging, ligand conjugated liposomes showed greater penetration in the clot than control. In in vivo studies (BALB/c mice; 28 days), the antibody titer was reduced ( p <0.05) in animals treated with ligand anchored liposomes (0.69 ± 0.14 AU) than those treated with free STK solution (0.81±0.12 AU). In comparison to free STK, the surface modified liposomes resulted in a significant reduction in immunogenicity. In addition the developed delivery system showed higher affinity and better clot penetration than control.