Curcumin-loaded nanoliposomes linked to homing peptides for integrin targeting and neuropilin-1-mediated internalization

Abstract

Context: Curcumin, a naturally occurring polyphenol, has been extensively studied for its broad-spectrum anticancer effects. The potential benefits are, however, limited due to its poor water solubility and rapid degradation which result in low bioavailability on administration.

Objectives: This study encapsulates curcumin in nanoliposomes including an integrin-homing peptide combined with a C end R neuropilin-1 targeting motif for targeted delivery and receptor-mediated internalization, respectively.

Materials and methods: The linear GHHNGR (Glycine–Histidine–Histidine–Asparagine–Glycine–Arginine) was synthesized through F-moc chemistry on 2-chlorotrityl chloride resin and conjugated to oleic acid. The lipoyl-peptide units were then co-assembled with lecithin and 0–75 mole % Tween-80 into liposomes. Curcumin was passively entrapped using a film hydration technique and its degradation profile was examined within seven consecutive days. The cytotoxic effects of the curcumin-loaded liposomes were studied on MCF-7 and MDA-MB-468, during 24 h exposure in MTT assay.

Results: The maximum curcumin entrapment (15.5% W/W) and minimum degradation (< 23%) were obtained in a pH switch loading method from 5.7 to 8, in nanoliposomes (< 50 nm) containing oleyl-peptide, lecithin and Tween-80 (1:1:0.75 mole ratio). The oleyl-peptide did not prove any haemolytic activity (< 1.5%) up to 10-fold of its experimental concentration. The curcumin-loaded liposomes displayed significant reduction in the viabilities of MCF-7 (IC₅₀ 3.8 μM) and MDA-MB-468 (IC₅₀ 5.4 μM).

Discussion and conclusion: This study indicated potential advantages of the peptide-conjugated liposomes in drug transport to the cancer cells. This feature might be an outcome of probable interactions between the targeted nanoliposomes with the integrin and neuropilin-1 receptors.

Keywords:

• Encapsulation
• stability
• endosome escape
• nanotechnology

Acknowledgements

We would like to thank Dr Alireza ghasempour for his expert technical assistance in peptide analysis and Dr Mohammad Reza Khorramizadeh for his critical advice in cellular experiments. We are also grateful to Dr Zahra Shahsavari for the donation of the cell lines and her experience in cellular analysis. The authors express special thanks to the Vice-Chancellor of Research of Tehran University of Medical Sciences for the grant award and financial support that enabled us to complete the present study.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

This research was supported by a grant [27715/Dec. 2014] from Tehran University of Medical Sciences, Medical Biomaterials Research Center.