Temperature sensitive liposomes of plumbagin: characterization and in vivo evaluation in mice bearing melanoma B16F1.
The effectiveness of the combination of thermosensitive liposomes of plumbagin and hyperthermia is described. Small-sized, thermosensitive liposomes were prepared by thin film hydration and subsequent sonication. The liposomes were characterized for size, phase transition temperature, in vitro drug release and stability. The results of particle size analysis indicated that almost 90% of the vesicles were below 0.19 microm size. The phase transition temperature of the liposomes as determined by differential scanning calorimetry was found to be 41.32 degrees C. The results of in vitro release studies in phosphate buffered saline + mouse plasma indicated that maximum drug release (51.25%) occurred at 42 degrees C compared to the less than 9% release at 37 degrees C. Better stability profile was observed when the plumbagin liposomes were stored at 4 degrees C. When combined with localised hyperthermia (43 degrees C, 30 min or 1 h), liposomal plumbagin administered intravenously to C57BL/6J mice bearing melanoma exhibited better anticancer activity as compared to animals treated with an equivalent dose of free plumbagin with or without hyperthermia, which was evident by enhanced volume doubling time and growth delay.
Tiwari
Sandip B
SB
Department of Pharmaceutics, College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576 119, Karnataka, India. sandiptiwari@zyduscadila.com
Pai
Raveendra M
RM
Udupa
N
N
D015060:1,2-Dipalmitoylphosphatidylcholine; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use*; D000465:Algorithms; D000818:Animals; D002152:Calorimetry, Differential Scanning; D004355:Drug Stability; D005079:Excipients; D005260:Female; D008081:Liposomes; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009285:Naphthoquinones / Q000008:administration & dosage* / Q000627:therapeutic use*; D010316:Particle Size; D013696:Temperature
D000276:Adjuvants, Immunologic; D005079:Excipients; D008081:Liposomes; D009285:Naphthoquinones; D015060:1,2-Dipalmitoylphosphatidylcholine; C014758:plumbagin