Design of a novel curcumin-soybean phosphatidylcholine complex-based targeted drug delivery systems

Abstract

Recently, the global trend in the field of nanomedicine has been toward the design of combination of nature active constituents and phospholipid (PC) to form a therapeutic drug-phospholipid complex. As a particular amphiphilic molecular complex, it can be a unique bridge of traditional dosage-form and novel drug delivery system. In thisarticle, on the basis of drug-phospholipid complex technique and self-assembly technique, we chose a pharmacologically safe and low toxic drug curcumin (CUR) to increase drug-loading ability, achieve controlled/sustained drug release and improve anticancer activity. A novel CUR-soybean phosphatidylcholine (SPC) complex and CUR-SPC complex self-assembled nanoparticles (CUR-SPC NPs) were prepared by a co-solvent method and a nanoprecipitation method. DSPE-PEG-FA was further functionalized on the surface of PEG-CUR-SPC NPs (designed as FA-PEG-CUR-SPC NPs) to specifically increase cellular uptake and targetability. The FA-PEG-CUR-SPC NPs showed a spherical shape, a mean diameter of about 180 nm, an excellent physiological stability and pH-triggered drug release. The drug entrapment efficiency and drug-loading content was up to 92.5 and 16.3%, respectively. In vitro cellular uptake and cytotoxicity studies demonstrated that FA-PEG-CUR-SPC NPs and CUR-SPC NPs presented significantly stronger cellular uptake efficacy and anticancer activity against HeLa cells and Caco-2 cells compared to free CUR, CUR-SPC NPs and PEG-CUR-SPC NPs. More importantly, FA-PEG-CUR-SPC NPs showed the prolonged systemic circulation lifetime and enhanced tumor accumulation compared with free CUR and PEG-CUR-SPC NPs. These results suggest that the FA targeted PEGylated CUR-SPC complex self-assembled NPs might be a promising candidate in cancer therapy.

Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy

“…Thus, the pH-responsive dual-drug release pattern of MTX-Imine-M-CUR might be facilitated to reduce the burst release and leakage of the drug. 17,41 In vitro cellular uptake CUR and M-CUR for the same incubation time ( Figures 3A and 4A). This result indicates the manner of time-dependent cellular uptake of CUR molecules and CUR-loaded nanoparticles.…”

“…After filtration by a 0.22 µm filter membrane, a part of the filtrate was analyzed for the determination of drug loading content by a high-performance liquid chromatography method as described in our previous studies. 17,41 The drug loading content of MTX-Imine-M-CUR was calculated as (amount of drug in MTX-Imine-M-CUR)/ (weight of MTX-Imine-M-CUR) ×100%.…”

“…[12][13][14] Curcumin (CUR), a natural polyphenol extracted from turmeric, has attracted increasing attention on account of its anticancer, antioxidant, anti-inflammatory, and hepatoprotective properties. [15][16][17][18] As a potent anticancer and antioxidant agent, CUR can inhibit cell proliferation of a large variety of tumors through topoisomerase II-mediated DNA cleavage. 19,20 Unfortunately, its clinical application has been severely restricted due to the poor stability, limited water solubility, and inadequate accumulation at the tumor sites.…”

Phytosomal Nanoparticles Preparation of Curcuminoids to Enhance Cellular Uptake of Curcuminoids on Breast Cancer Cell Line MCF-7

“…Taken together, these results proved the presence of hydrogen bonds interaction between curcuminoids and polar head of HEPC coupled with insertion of cholesterol into the membranes of Curs-Phyto which led to the physicochemical stability of phytosomal nanoparticles. 25,30 This might be facilitated for the enhancement in cellular uptake of Curs-Phyto via oral administration. In vitro drug release profiles Figure 6 showed the in vitro drug release profiles of Curs-Phyto separately calculated for Cur, DMC and BDMC.…”

“…The similar structure component and high affinity between the phospholipid on the phytosome Curs-Phyto's surface phospholipid and cell membranes are crucial determinants. 30 Phytosome can easily move from a hydrophilic environment into the lipophilic environment of the cell membrane and then enter the cell. 33 Our data demonstrated that Curs-Phyto exhibited higher association and internalization into the cells compared to that of free curcuminoids, which proved that the phytosomal formulation has a profound impact on the uptake of curcuminoids.…”