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The butyryl galactose ester-modified coix component microemulsions (But-Gal-CMEs) was developed for enhanced liver tumor-specific targeting. The study was aimed to evaluate the hepatoma-targeting potential of But-Gal-CMEsin vitroandin vivo. But-Gal-CMEs with a uniform spherical shape exhibited a small particle size (56.68 ± 0.07 nm), a narrow polydispersity (PDI, 0.144 ± 0.005) and slightly negative surface charge (−0.102 ± 0.008 mV). In the cell uptake studies, But-Gal-CMEs showed a significant enhancement on the intracellular fluorescent intensity on HepG2 cells model, which was 1.93-fold higher relative to coix component microemulsions (CMEs). The IC50of But-Gal-CMEs against HepG2 cells was 64.250 μg/mL, which was notably stronger than that of CMEs. In the cell apoptosis studies, compared with CMEs, But-Gal-CMEs (50 μg/mL) treatment resulted in a 1.34-fold rise in total apoptosis cells of HepG2. In the biodistribution studiesin vivo, the intratumorous fluorescence of Cy5-loaded But-Gal-CMEs was 1.43-fold higher relative to that of Cy5-loaded CMEs, suggesting an obviously enhanced accumulation in the tumor sites. Taken as together, But-Gal could be incorporated into the coix component microemulsions as a novel ligand for realizing hepatoma-targeting drugs delivery. [ABSTRACT FROM AUTHOR]

The accumulation and penetration of antitumor drugs in tumor tissues are directly related to their antitumor effects. The particle size of the nanodrug delivery system is one of the most important factors for the accumulation and penetration of antitumor drugs within tumor tissues. Generally, nanodelivery systems of intermediate size (100–120 nm) are capable of efficient accumulation owing to prolonged circulation and enhanced permeability and retention (EPR) effect; however, smaller ones (20–40 nm) are effective for deep penetration within tumor tissue. Currently a conventional drug delivery system cannot possess two types of optimal sizes, simultaneously. To solve this and to enhance cervical cancer treatment, a furin-responsive triterpenine-based liposomal complex (PEGcleavable Tf-CTM/L), with Tf-CTM (transferrin-modified tripterine-loaded coix seed oil microemulsion) in core, coated with a thermo-sensitive lipid and a kind of PEG shell modified with a furin-cleavable peptide was developed to improve tumor-specific accumulation and penetration. Herein, PEGcleavable Tf-CTM/L was capable of efficient accumulation because of EPR effect. The PEG shells could timely detach under stimulation of overexpressed furin protein to solve the problem of the steric hindrance dilemma. The small-sized Tf-CTM released under stimulation of tumor microthermal environment in cervical cancer, which was efficient with regards to deep penetration at tumor sites. Notably, compared to the use of triterpenine alone, PEGcleavable Tf-CTM/L promoted anticervical efficacy and displayed diminished systemic toxicity by efficient accumulation and deep penetration of antitumor drugs within tumor tissues. Our study provides a new strategy, and holds promising potential for anticervical cancer treatment. [ABSTRACT FROM AUTHOR]

The aim of this study is to explore the influence of Ganoderma lucidum-derived polysaccharides (GLP) to coix oil-based microemulsion on pharmaceutical performance and anti-lung cancer treatment. GLP-integrated coix oil-based microemulsion (MEs(PS-GLP)) exhibited a clear spherical shape, small particle size, and good hydrodynamics similar to the coix oil-based microemulsion, but showed a lower zeta potential and a better stability. Fluorescence resonance energy transfer analysis presented that GLP was integrated with microemulsion as a single system. Notably, the average molecular distance between polysaccharide and microemulsion was approximately 1.7 nm. The half-maximal inhibitory concentration of MEs(PS-GLP) against A549 cells was about 119 μg/mL. In vivo imaging studies showed that introduction of GLP promoted the tumor-specific accumulation of microemulsion in comparison with controls. In vivo, antitumor results showed that MEs(PS-GLP) markedly inhibited the tumor growth of A549-bearing xenograft nude mice and obviously improve the serum immune index. Collectively, this study demonstrates the potential mechanism of spatial relation between polysaccharides and microemulsion and validates the significances of GLP on tumoral accumulation and antitumor efficacy. [ABSTRACT FROM AUTHOR]

Aminoglycoside-induced hair cell (HC) loss is a major cause of hearing impairment, and the effective prevention of HC loss remains an unmet medical need. Epigenetic mechanisms have been reported to be involved in protecting cochlear cells against ototoxic drug injury, and in this study we developed new bioactive compounds that have similar chemical structures as the epigenetics-related lysine-specific demethylase 1 (LSD1) inhibitors. LSD1 inhibitors have been reported to protect cochlear cells by preventing demethylation of dimethylated histone H3K4 (H3K4me2). To determine whether these new compounds exert similar protective effects on HCs, we treated mouse cochlear explant cultures with the new compounds together with gentamycin. There was a severe loss of HCs in the organ of Corti after gentamycin exposure, while co-treatment with the new compounds significantly protected against gentamycin-induced HC loss. H3K4me2 levels in the nuclei of HCs decreased after exposure to gentamycin, but H3K4me2 levels were maintained in the presence of the new compounds. Apoptosis is also involved in the injury process, and the new compounds protected the inner ear HCs against apoptosis by reducing caspase-3 activation. Together, our findings demonstrate that our new compounds prevent gentamycin-induced HC loss by preventing the demethylation of H3K4me2 and by inhibiting apoptosis, and these results might provide the theoretical basis for novel drug development for hearing protection. [ABSTRACT FROM AUTHOR]

The aim of this study is to explore the influence of Ganoderma lucidum-derived polysaccharides (GLP) to coix oil-based microemulsion on pharmaceutical performance and anti-lung cancer treatment. GLP-integrated coix oil-based microemulsion (MEs(PS-GLP)) exhibited a clear spherical shape, small particle size, and good hydrodynamics similar to the coix oil-based microemulsion, but showed a lower zeta potential and a better stability. Fluorescence resonance energy transfer analysis presented that GLP was integrated with microemulsion as a single system. Notably, the average molecular distance between polysaccharide and microemulsion was approximately 1.7 nm. The half-maximal inhibitory concentration of MEs(PS-GLP) against A549 cells was about 119 μg/mL. In vivo imaging studies showed that introduction of GLP promoted the tumor-specific accumulation of microemulsion in comparison with controls. In vivo, antitumor results showed that MEs(PS-GLP) markedly inhibited the tumor growth of A549-bearing xenograft nude mice and obviously improve the serum immune index. Collectively, this study demonstrates the potential mechanism of spatial relation between polysaccharides and microemulsion and validates the significances of GLP on tumoral accumulation and antitumor efficacy. [ABSTRACT FROM AUTHOR]

Aminoglycoside-induced hair cell (HC) loss is a major cause of hearing impairment, and the effective prevention of HC loss remains an unmet medical need. Epigenetic mechanisms have been reported to be involved in protecting cochlear cells against ototoxic drug injury, and in this study we developed new bioactive compounds that have similar chemical structures as the epigenetics-related lysine-specific demethylase 1 (LSD1) inhibitors. LSD1 inhibitors have been reported to protect cochlear cells by preventing demethylation of dimethylated histone H3K4 (H3K4me2). To determine whether these new compounds exert similar protective effects on HCs, we treated mouse cochlear explant cultures with the new compounds together with gentamycin. There was a severe loss of HCs in the organ of Corti after gentamycin exposure, while co-treatment with the new compounds significantly protected against gentamycin-induced HC loss. H3K4me2 levels in the nuclei of HCs decreased after exposure to gentamycin, but H3K4me2 levels were maintained in the presence of the new compounds. Apoptosis is also involved in the injury process, and the new compounds protected the inner ear HCs against apoptosis by reducing caspase-3 activation. Together, our findings demonstrate that our new compounds prevent gentamycin-induced HC loss by preventing the demethylation of H3K4me2 and by inhibiting apoptosis, and these results might provide the theoretical basis for novel drug development for hearing protection. [ABSTRACT FROM AUTHOR]

Previously, we have developed a multicomponent-based microemulsion composed of etoposide, coix seed oil, and ginsenoside Rh2 (ECG-MEs). In this study, our goal was to validate the feasibility of ECG-MEs in lung cancer treatment and explore the mechanism underling the enhanced antitumor efficacy. The optimal weight ratio of ginsenoside Rh2 (G-Rh2) in ECG-MEs was determined as 3% (wt%), that was capable of forming the microemulsion readily with small particle size and high drug encapsulation efficiency. In cellular studies, the intracellular fluorescence of human non-small cell lung cancer (A549) cells treated with fluorescein isothiocyanate-labeled ECG-MEs (FITC/ECG-MEs) was significantly higher than that of various controls, leading to the obviously synergistic anticancer activities in cytotoxicity andin vitrocell apoptosis induction. The anticancer efficacyin vivoresults showed that ECG-MEs markedly inhibited the growth of A549 tumor xenografts, potently induced tumor cells apoptosis, and obviously prolonged the survival time of mice. Of note, the mechanisms of enhanced anticancer efficiency were connected with the small size-mediated deep tumor penetration and increase in serum concentration of T helper 1 (Th1) cytokines. In summary, ECG-MEs exerting the rational drug combination strategy offers a solid evidence for lung cancer treatment, and has a promising potential for clinical application. [ABSTRACT FROM AUTHOR]