Development and characterization of site specific target sensitive liposomes for the delivery of thrombolytic agents.
In recent times, search for potent and highly selective thrombolytic agents with minimal side effects has become a major area of research. The aim of the present study was to develop and characterize target sensitive (TS) liposomes encapsulating streptokinase, a thrombolytic agent. The developed TS liposomes were composed of dioleylphophatidyl ethanolamine (DOPE) and dipalmityl-c(RGDfK) (10:1mol/mol). Dipalmityl-c(RGDfK) was synthesized using typical carbodiimide chemistry using palmitic acid and c(RGDfK), while lysine was used as a spacer. Liposomes were of 100-120nm size. In vitro drug release study showed that nearly 40% drug of the entrapped drug was released in 12h in the PBS (pH 7.4), however on incubation with activated platelet about 90% of drug was released within 45min. The results suggested target sensitivity of the liposomes. Further, targeting potential was confirmed using fluorescent microscopy and flow cytometry. Clot lysis study revealed that TS liposomes could not only reduce the clot lysis time but also increase the extent of clot lysis as compared to non-liposomal streptokinase solution. In conclusion, the present liposomal formulation will target the thrombolytic agent to the activated platelets in the thrombus and hence will improve the therapeutic efficacy of the drug.
Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar, MP 470003, India.
Bhuvaneshwar
B
Vaidya
Manasa K
MK
Nayak
Debabrata
D
Dash
G P
GP
Agrawal
Suresh P
SP
Vyas
D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008081:Liposomes; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010169:Palmitic Acids / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011485:Protein Binding; D013300:Streptokinase / Q000008:administration & dosage* / Q000378:metabolism; D013379:Substrate Specificity
D005343:Fibrinolytic Agents; D008081:Liposomes; D009842:Oligopeptides; D010169:Palmitic Acids; D010714:Phosphatidylethanolamines; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C094877:dioleoyl phosphatidylethanolamine; C047981:arginyl-glycyl-aspartic acid; D013300:Streptokinase