A microemulsion co-loaded with Schizandrin A–docetaxel enhances esophageal carcinoma treatment through overcoming multidrug resistance

Abstract

Multidrug resistance (MDR) is the major underlying cause of the low 5-year survival rate of esophageal carcinoma. In this study, we developed a novel microemulsion system (SD-ME) co-loaded with docetaxel (DTX) and Schizandrin A, a potent chemotherapeutic agent and a potential drug resistance modulator, respectively. In the physicochemical characterization studies, SD-ME displayed a well-defined spherical shape and size (56.62 ± 4.16 nm), a narrow polydispersity index (PDI, 0.132 ± 0.002), and a negative surface charge (-19.81 ± 3.11 mv). In the cellular uptake studies, SD-ME with a DTX concentration of 30 μg/mL exhibited a 3.9-fold enhancement of DTX internalization in DTX-resistant EC109 (EC109/DDR) cells in comparison to that observed for EC109 cells, and the mechanisms were associated with reducing P-gp expression and inhibiting P-gp ATPease. The half-maximal inhibitory concentrations (IC) of DTX and SD-ME against EC109/DDR cells were 40.57 ± 0.39 and 3.59 ± 0.06 μg/mL, respectively. Likewise, the apoptotic rate of EC109/DDR treated with SD-ME increased up to 20-fold compared to that observed with free DTX. In anticancer efficacy studies in vivo, SD-ME markedly retarded the tumor growth of nude mice bearing EC109/DDR tumor xenografts compared with D-ME and free DTX throughout the duration of study. Consequently, mice treated with SD-ME had the highest survival rate (37.5%) during the observation period (70 days). In addition, there were no apparent side effects after the administration of SD-ME. Overall, our study provides evidence for SD-ME as an effective drug delivery system for enhanced MDR tumor treatment.

Curcumin-Loaded Solid Lipid Nanoparticles Enhanced Anticancer Efficiency in Breast Cancer

“…Furthermore, fluoresceine isothiocyanate (FITC)-conjugated Annexin V and propidium iodide (PI) were used to measure the numbers of apoptotic and necrotic cells [ 19 ]. As seen in Figure 5 A, when cells were treated with free curcumin, the apoptosis rates were gradually increased from 11.18% to 29%.…”

Transferrin-Conjugated Docetaxel–PLGA Nanoparticles for Tumor Targeting: Influence on MCF-7 Cell Cycle

“…Docetaxel trihydrate (DCT) is a second generation taxane derived from a compound found in the European yew tree Taxus baccata [31]. The drug is practically insoluble in water and is being currently used in chemotherapy of gastro/esophageal [32,33,34,35,36] and breast [37,38,39,40] cancers. It binds precisely to the β-tubulin subunit of microtubules and antagonizes the disassembly of this key cytoskeletal protein, with the result that bundles of microtubules and aberrant structures, derived from the microtubules, appear in the mitotic phase of the cell cycle.…”

SYL3C aptamer-anchored microemulsion co-loading β-elemene and PTX enhances the treatment of colorectal cancer

“…SYL3C/EP-MEs was prepared by one-step emulsion method as described previously but with some modifications (Qu et al., 2014, 2015; 2017; Su et al., 2017; Zhang et al., 2019). First, 4 ∼ 40 mg of PTX and 80 mg of β-elemene were simultaneously dissolved in 220 mg of 1944 CS with a vigorous stirring for 2 h. Next, 170 mg of DOPE, 120 mg of HS15 and 10 mg of Mal-DSPE-PEG were added to the above-mentioned homogeneous mixture in batches.…”

“…The main physicochemical parameters of SYL3C/EP-MEs were measured by a dynamic light scattering (DLS) (Zetasizer Nano ZS90, Malvern, UK). Various samples diluted as 1 mg/mL (total mass concentration) were injected into the sample cell to obtain the average size, polydispersity (PDI) distribution and zeta potential according to the protocol of operation (Su et al., 2017). As reported previously, the morphology was characterized by transmission electron microscopy (TEM, JEOL-100CXII, Japan) (Qu et al., 2014; 2017).…”