Hyaluronan coated liposomes as the intravenous platform for delivery of imatinib mesylate in MDR colon cancer

作者：Negi Lalit Mohan; Jaggi Manu; Joshi Vidushi; Ronodip Kar; Talegaonkar Sushama^*

来源：International Journal of Biological Macromolecules, 2015, 73: 222-235.

DOI：10.1016/j.ijbiomac.2014.11.026

• P-glycoprotein
• Box-Behnken
• Imatinib
• Liposome
• CD-44
• Hyaluronic acid

Imatinib mesylate has been evaluated for possible potential in treatment of colon cancer in recent times. However, due to significant reporting of P-gp expression in colon cancer, it can come across set back due to MDR. Therefore, in present work the liposomal formulation containing imatinib-bile salt conjugate was developed and investigated for its comparative performance in MDR colon cancer cells and surface modified with hyaluronic acid for achieving low hemotoxicity with stealth characteristics. Imatinib was successfully conjugated with sodium-deoxycholate by charged conjugation and evaluated through FTIR, DSC and PXRD. The developed conjugate (IM-SD) was encapsulated in liposomes and the conditions were optimized by Box-Behnken statistical design to achieve a size of 56.56 +/- 1.23 nm along with 99.11 +/- 0.89% entrapment efficiency (LIPO). The liposomes were surface modified with hyaluronic acid and the size was enhanced to 159.14 +/- 3.2 nm (HA-LIPO). Flow cytometric studies demonstrated the enhanced uptake of P-gp substrate rhodamine dye in P-gp positive colo 320 colon cancer cells. In addition, an enhanced cellular internalization of HA-LIPO in CD-44 positive HT-29 and colo 320 cells indicates the targeting attributes of the hyaluronan coated liposomes. Finally, the hyaluronan coated liposomes were also found to have low opsonization activity.

• 出版日期2015-2