Formulation and in vitro evaluation of curcumin-lactoferrin conjugated nanostructures for cancerous cells

Abstract

Curcumin, a natural polyphenol, exhibits anti-oxidant, anti-inflammatory, anti-neoplastic and chemopreventive properties. In fact, targeting of this natural anticancer agent has received a great deal of attention during the recent years. In this study, we proposed that curcumin conjugation with lactoferrin molecules may lead to a potential drug delivery system targeted toward cancerous cells through both active and passive targeting. In this regard, curcumin conjugated lactoferrin was developed via a carbodiimide-based coupling reaction and the resulting conjugates were appraised for their molecular properties as a potential targeted drug delivery system. The mean diameter of the designed nanostructure was about 165 ± 26 nm with a PDI of 0.308 ± 0.045. The conjugated nanostructures showed a considerably improved cytotoxicity on HCT116 cells as illustrated by MTT assay along with a higher level of cellular uptake. Cellular uptake and targeting capability of conjugated samples were further investigated by confocal microscopy and the conjugated curcumin nanostructures showed an enhanced efficacy compared to curcumin. Furthermore, flow cytometry analysis proved that early apoptosis occurred in HCT116 cell line, after 24 h incubation with conjugated curcumin.

Macrophage repolarization using CD44-targeting hyaluronic acid–polylactide nanoparticles containing curcumin

“…Nanomedicine approach appears an effective strategy for enhancing the efficiency of curcumin in therapeutic applications [30,31]. Using a variety of nanoformulation such as polymeric NPs, gold/magnetic NPs, liposomes, micelles and dendrimers for the encapsulation of curcumin has been demonstrated successful in improving its effectiveness in treating various diseases, especially different types of cancers and inflammatory disorders and importantly, some of these nanoformulated curcumin could be translated after preclinical experiments and human clinical trials [10,32,33].…”

Determination and pharmacokinetic study of isothiouronium-modified pyrimidine-substituted curcumin analog (1G), a novel antitumor agent, in rat plasma by liquid chromatography–tandem mass spectrometry

“…Moreover, cell culture experiments have shown the antitumor activity of curcumin in various human cancer cell lines, such as leukemia [9], esophageal cancer [10], gastric cancer [11], liver cancer [12], lung cancer [13] and cervical cancer [14]. Despite the potential therapeutic effects of curcumin, clinical applications are restricted by its poor bioavailability, rapid metabolism, low solubility and extensive rapid excretion [15][16][17][18][19][20]. These inherent problems prompted us to synthesize novel isothiouronium-modified pyrimidinesubstituted curcumin analogs [21][22][23] with improved pharmacokinetic profiles.…”

Lactoferrin, a multi-functional glycoprotein: Active therapeutic, drug nanocarrier & targeting ligand

“… [ 104 ] Lf NPs Nab technology Oleanolic acid Improved bioavailability Increased dissolution and enhanced oral absorption of OA. [ 105 ] Lf-Drug conjugate Carbodiimide coupling CUR Colorectal cancer Lower IC 50 of NPs (0.5 μg/ml) against HCT116 cells than free curcumin (3.3 μg/ml) after 48 h. [ 112 ] Lf-Drug conjugate Carbodiimide coupling DOX Prostate cancer Orally Fe-bLf-DOX inhibited tumor growth, prolonged survival, reduced DOX toxicity. [ 77 ] Lf-Drug conjugate Free-radical graft copolymerization EGCG CA Gallic acid Antioxidant Higher antioxidant activity of Lf-polyphenol conjugates than control Lf in both ABTS scavenging and reducing power assays.…”

“…Utilizing the hydrophilic property of Lf in enhancing the water solubility of the hydrophobic drugs where the conjugated structures drive the self-assembly forming nano-micelles in aqueous media. Chaharband et al has prepared Lf-curcumin conjugate where the carboxylic moiety of Lf was activated via carbodiimide reagent and then coupled to the hydroxyl group of curcumin forming an ester bond [ 112 ]. The conjugate of curcumin to Lf macromolecule was self-assembled into nanostructures with a size of 165 nm.…”