101P - Smart delivery of lapatinib to reduce its cardiotoxicity: A 99mTc labeled biodistribution study

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer
Presenter Amit Khanna
Citation Annals of Oncology (2015) 26 (suppl_3): 31-33. 10.1093/annonc/mdv121
Authors A. Khanna1, A.T. Khanna2, N. Gupta1, S. Trivedi1
  • 1New Drug Delivery System, VNS Faculty of Pharmacy, 462044 - Bhopal/IN
  • 2Pharmacology, Globus College of Pharmacy, 462044 - Bhopal/IN

Abstract

Body

Objective: The research work aimed to reduce the cardiotoxicity of lapatinib, anti-HER-2 agent, used in treatment of HER-2 positive breast cancer. Overexpression of HER-2 in breast cancer is associated with large tumor size, poor differentiation, and poor clinical outcomes. However, HER-2 pathway plays a significant role in heart too, where it is involved in the regulation of cellular metabolism, growth and survival through activation of important signaling pathways, such as phosphoinositide 3-kinase/AKT signaling. Inhibition of HER-2 receptors in the breast is desirable for its therapeutic benefit but their blockage in the heart is related to its associated cardio-toxicity.

Experimentation: PEGylated liposomes of lapatinib were formulated by lipid layer hydration method. Different ratios of lipid and drug were tried to prepare the liposomes with maximum drug entrapment. The optimized formulation with maximum drug loading was promoted for in vivo biodistribution study, after 99mTc labeling, in rats xenografted with MCF-7 breast cancer cell line. The biodistribution of the liposomes in heart and cancerous tissue was compared to that of free drug.

Results: The maximum entrapment efficiency of the liposomes was found to be 76.4 ± 3.8 %. The labelling efficiency was almost the same up to 120 min after incubation for lapatinib and its liposomes. Less than 2% radioactivity was dissociated after 6 hours incubation in the saline which indicates the suitability of the complex for its in vivo use. Results of biodistribution revealed maximum radioactivity at the cancerous site i.e. breast compared to the cardiac tissue at all the time points.

Conclusion: PEGylated liposomes of lapatinib, due to its EPR effect, is a smart drug delivery system that has the dual advantages of bypassing the heart as well as accumulating in the cancerous tissue.

Disclosure: All authors have declared no conflicts of interest.