Objectives
Multidrug resistance (MDR) remains a primary challenge in breast cancer treatment. In the present study, D‐alpha‐tocopheryl polyethylene glycol 1000 succinate (TPGS)‐coated docetaxel‐loaded liposomes were developed as a novel drug delivery system to reverse MDR and enhance breast cancer therapy compared with the traditional liposomes, DSPE‐mPEG‐coated liposomes (stealth liposomes) and commercial Taxotere®.
Key findings
Liposomes were prepared by thin – film dispersion method. Evaluations were performed using human breast cancer MCF‐7 and resistant MCF‐7/ADR cells. The reversal multidrug‐resistant effect was assessed by P‐gp inhibition assay, cytotoxicity, cellular uptake and apoptosis assay.
Results
The TPGS‐chol‐liposomes were of an appropriate particle size (140.0 ± 6.0 nm), zeta potential (−0.196 ± 0.08 mv), high encapsulation efficiency (99.0 ± 0.9) and favourable in vitro sustained release. The TPGS‐coated liposomes significantly improved cytotoxicity and increased the intracellular accumulation of docetaxel in both types of breast cancer cells. The TPGS‐coated liposomes were confirmed to induce apoptosis via a synergistic effect between docetaxel and TPGS. It was demonstrated that TPGS enhanced the intracellular accumulation of drug by inhibiting overexpressed P‐glycoprotein.
Conclusions
The TPGS‐conjugated liposomes showed significant advantages in vitro compared with the PEG‐conjugated liposomes. The TPGS‐conjugated liposomes could reverse the MDR and enhance breast cancer therapy.
The cationic dimethyldioctadecylammonium/trehalose 6,6,9-dibehenate (DDA/TDB) liposome is as a strong adjuvant system for vaccines, with remarkable immunostimulatory activity. The mucosal administration of vaccines is a potential strategy for inducing earlier and stronger mucosal immune responses to infectious diseases. In this study, we assessed whether the intranasal administration of cationic DDA/TDB liposomes combined with influenza antigen A (H3N2) can be used as a highly efficacious vaccine to induce mucosal and systemic antibody responses. Confocal laser scanning microscopy and a flow-cytometric analysis showed that the uptake of the cationic DDA/TDB liposome carrier was significantly higher than that of neutral 1,2-distearoyl-sn-glycero-3-phosphocholine/cholesterol (DSPC/Chol) or cationic 1,2-dioleoyl-3-trimethylammonium-propane/3β-(N-[N',N'-dimethylaminoethane]-carbamoyl (DOTAP/DC-Chol) liposomes. Our results indicate that the cationic DDA/TDB liposome is more effective in facilitating its uptake by dendritic cells (DCs) in vitro than the DSPC/Chol or DOTAP/DC-Chol liposome. DCs treated with DDA/TDB liposomes strongly expressed CD80, CD86, and MHC II molecules, whereas those treated with DSPC/Chol or DOTAP/DC-Chol liposomes did not. C57BL/6 mice intranasally immunized with H3N2-encapsulating cationic DDA/TDB liposomes had significantly higher H3N2-specific s-IgA levels in their nasal wash fluid than those treated with other formulations. The DDA/TDB liposomes also simultaneously enhanced the serum IgG IgG2a, IgG1, and IgG2b antibody responses. In summary, DDA/TDB liposomes effectively facilitated their uptake by DCs and DCs maturation in vitro, and induced significantly higher mucosal IgA, systemic IgG, IgG1, and IgG2b antibody titres than other formulations after their intranasal administration in vivo. These results indicate that DDA/TDB liposomes are a promising antigen delivery carrier for clinical antiviral applications.
These findings highlight the fitness of spray congealing to co-deliver multiple drugs, which open new perspectives for the development of more advanced combination of multiple therapeutic agents, presumably improving the bioavailability and therapeutic efficacy.
Aim
This study examined the mediating effect of circadian rhythm amplitude (LV) and stability (FR) between work stress and sleep quality among Chinese shift‐working nurses (SWNs).
Design
A cross‐sectional study.
Methods
Three‐hundred and seventy‐nine nurses working in shifts were investigated by convenient sampling from six hospitals in Shanghai, China. The mediating effect was analysed using the structural equation model with bootstrapping procedures.
Results
Work stress could directly affect shift nurses' sleep quality and indirectly affect sleep quality through circadian rhythm amplitude and stability. The total indirect effects of work stress on sleep quality accounted for 36.7% of the total effect. The study revealed that poor sleep quality is very common among SWNs, which deserves attention. The mediating effect of the circadian rhythm provides new insights to improve sleep quality, not only by lightening the work stress but also by improving circadian rhythm in SWNs.
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