Curcumin-Loaded Nanoliposomes Linked to Homing Peptides for Integrin Targeting and Neuropilin-1- Mediated Internalization Publisher Pubmed



Kangarlou S¹ ; Ramezanpour S² ; Balalaie S² ; Roudbar Mohammadi S³ ; Haririan I^{1, 4}
Source: Pharmaceutical Biology Published:2017

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. © 2016 The Author(s).