48P - Drug delivery of trastuzumab to bypass the associated cardiotoxicty-A 99Tc radiolabelled bio-distribution study.

Date 04 May 2017
Event IMPAKT 2017
Session Welcome reception and Poster Walk
Topics Breast Cancer
Presenter Anshu Thakur
Authors A. Thakur, V. Dhote
  • Pharmacy, vns faculty of pharmacy, 462044 - bhopal/IN



Objective: Almost 33% of breast cancers are associated with over expression of human epidermal growth factor receptor 2 (HER2). Inhibiting these overexpressed HER-2 receptors in the breast is desirable. However, this inhibition never happens in isolation. HER-2 pathway in the heart, involved in the regulation of normal cellular metabolism, growth and survival, is also inhibited which leads to serious cardiotoxicity. The research was aimed to design a delivery system for Trastuzumab which can bypass the cardiotoxicity without compromising the desired therapeutic action at breast.

Experimentation: Trastuzumab was entrapped into PEGylated liposomes by lipid layer hydration technique. To ensure the maximum entrapment, different ratios of Trastuzumab and lipids were utilised. The optimised formulation with maximum entrapment was labelled with 99 m Tc. In vivo biodistribution study was performed in rats xenografted with MCF-7 breast cancer cell lines to compare the biodistribution in heart and the breast tissues.

Results: Percent entrapment efficiency (%EE) of Trastuzumab in liposomes was found to be 79.7 ± 8.2%. The labelling efficiency almost same upto 90 min after incubation for trastuzumab and 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 th that in the case of 99mTc-liposomes, the radioactivity present in the cancerous breast was more at all the time points compared to heart

Conclusion: PEGylated liposomes seems to be a promising delivery to overcome the cardiomyopathy associated with Trastuzumab. Pegylated lipid system spends very less time in heart due to lymphatic drainage. And whatever time it spends in heart, its shielded by the lipid barrier.

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