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.

Synthesis and in vitro evaluation of natural drug loaded polymeric films for cardiovascular applications

“…Sogol et al, has also formulated the nanoliposomes loaded with curcumin and reported the nanoliposomes to be non-hemolytic. 50 In another study published in 2021, 51 researchers have synthesized the electrospun nanocomposite wound dressing composed of carboxymethyl guar gum and graphene oxide loaded with curcumin. They conducted various in vitro testing along with hemolysis test and reported the hemolytic activity of the curcumin loaded nanocomposite falls within the range of non-hemolytic category by showing hemolysis maximum of 2.95%.…”

Innovative Delivery Systems Loaded with Plant Bioactive Ingredients: Formulation Approaches and Applications

“…Galangin-loaded liposomes have been designed to target liver tissue [ 51 ], while a curcumin liposomal system has been developed to target cancer cells [ 52 ]. Fourth generation of liposomes (or theranostic liposomes) combine several strategies to achieve site-specific delivery and, at the same time, imaging [ 53 ]. Their main advantage is the multifunctionality—being diagnostic and therapeutic agents at the same time.…”

“…Fourth generation of liposomes (or theranostic liposomes) combine several strategies to achieve site-specific delivery and, at the same time, imaging [ 53 ]. Their main advantage is the multifunctionality—being diagnostic and therapeutic agents at the same time.…”

Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers

“…Furthermore, the entrapped curcumin exhibited a prolonged half-life and reduced degradation, in contrast to the free drug, in aqueous suspensions. 144 Simion et al also demonstrated that lipid nanoemulsion-loaded curcumin (CmLN) conjugated with a nona-arginine peptide (R 9 -CmLN) exhibited significantly higher uptake and internalization of R 9 -CmLN compared to nonfunctionalized CmLN in human endothelial cells. 145 Furthermore, Das et al synthesized RGDK-lipopeptides and functionalized these noncovalently with singlewalled carbon nanotubes (SWNTs) to form RGDK-SWNT.…”