Bitargeted microemulsions based on coix seed ingredients for enhanced hepatic tumor delivery and synergistic therapy

• Published in: International journal of pharmaceutics Vol. 503; no. 1-2; pp. 90 - 101
• Main Authors: Qu, Ding, Sun, Wenjie, Liu, Mingjian, Liu, Yuping, Zhou, Jing, Chen, Yan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.04.2016
• Subjects: Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Antineoplastic treatment; Apoptosis - drug effects; Cell Survival - drug effects; Coix; Coix seed oil; Coix seed polysaccharide; Emulsions; Galactose - chemistry; Hep G2 Cells; Hepatic tumor bitargeting; Humans; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Mice, Inbred ICR; Mice, Nude; Multicomponent microemulsions; Plant Oils - administration & dosage; Plant Oils - chemistry; Plant Oils - pharmacology; Plant Oils - therapeutic use; Polysaccharides - administration & dosage; Polysaccharides - chemistry; Polysaccharides - pharmacology; Polysaccharides - therapeutic use; Seeds; Tumor Burden - drug effects; Antineoplastic treatment; Coix seed polysaccharide; Hepatic tumor bitargeting; Coix seed oil; Multicomponent microemulsions
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.03.001

[Display omitted] A hepatic tumor bitargeted microemulsions drug delivery system using coix seed oil and coix seed polysaccharide (CP) acting as anticancer components, as well as functional excipients, was developed for enhanced tumor-specific accumulation by CP-mediated enhancement on passive tumor targeting and modification of galactose stearate (tumor-targeted ligand). In the physicochemical characteristics studies, galactose stearate-modified coix seed multicomponent microemulsions containing 30% CP (w%) (Gal-C-MEs) had a well-defined spherical shape with a small size (47.63±1.41nm), a narrow polydispersity index (PDI, 0.101±0.002), and a nearly neutral surface charge (−4.37±1.76mV). The half-maximal inhibitory concentration (IC50) of Gal-C-MEs against HepG2 cells was 70.2μg/mL, which decreased by 1.8-fold in comparison with that of coix seed multicomponent microemulsions (C-MEs). The fluorescence intensity of fluorescein isothiocyanate (FITC)-loaded Gal-C-MEs (FITC-Gal-C-MEs) internalized by HepG2 cells was 1.8-fold higher than that of FITC-loaded C-MEs (FIT C-C-MEs), but the cellular uptake of the latter became reduce by 1.6-fold when the weight ratio of CP decreased up to 10%. In the cell apoptosis studies, C-MEs (containing 30% CP) did not show a significant difference with Gal-C-MEs, but exhibited 3.3-fold and 1.5-fold increase relative to C-MEs containing 10% CP and 20% CP, respectively. In the in vivo tumor targeting studies, Cy5-loaded Gal-C-MEs (Cy5-Gal-C-MEs), notably distributed in the tumor sites and still found even at 48h post-administration, displayed the strongest capability of tumor tissue accumulation and retention among all the test groups. Most importantly, Gal-C-MEs had stronger inhibition of tumor growth, prolonged survival time and more effectively tumor cell apoptosis induction in comparison with C-MEs containing different amounts of CP, which further confirmed that a certain amount of CP and tumor-targeted ligand were of great importance to potent anticancer efficacy. The aforementioned results suggested that Gal-C-MEs presented promising potential as a highly effective and safe anticancer drug delivery system for enhanced liver cancer delivery.