Development and characterization of docetaxel-loaded lecithin-stabilized micellar drug delivery system (LsbMDDs) for improving the therapeutic efficacy and reducing systemic toxicity.

In the present study, we attempted to develop a lecithin-stabilized micellar drug delivery system (LsbMDDs) for loading docetaxel (DTX) to enhance its therapeutic efficacy and minimize systemic toxicity. A novel DTX-loaded LsbMDDs was optimally prepared by a thin-film hydration method and then hydrated with a lecithin nanosuspension while being subjected to ultrasonication. Physical characteristics of the optimized DTX-loaded LsbMDDs formulations were examined and found to have a mean size of <200 nm, an encapsulation efficiency of >90%, and drug loading of >6% with stability at room temperature and at 4 °C being longer than 2 and 7 days, respectively. The in vitro release of DTX from the DTX-loaded LsbMDDs was slower than that from the generic product of DTX (Tynen®). A cell viability assay demonstrated that the LsbMDDs showed better cytotoxicity than Tynen® against CT26 cancer cells. The in vivo antitumor efficacy of the DTX-loaded LsbMDDs was observed to be better than that of Tynen® in a CT26 tumor-bearing mice model. A high-dose regimen of the DTX-loaded LsbMDDs formulation showed greater inhibition of DU145 tumor growth than did Tynen®, but with less to similar systemic toxicity. An in vivo study also showed that a greater amount of drug was able to accumulate in the tumor site with the DTX-loaded LsbMDDs, and its maximal tolerable doses for single and repeated injections were 2-2.5-fold higher than those of Tynen®. In conclusion, the LsbMDDs could be a promising high drug-loaded nanocarrier for delivering hydrophobic chemotherapeutic agents that can enhance the efficacy of chemotherapy and reduce systemic toxicity.

In vitro anti-inflammatory properties of fermented pepino (Solanum muricatum) milk by γ-aminobutyric acid-producing Lactobacillus brevis and an in vivo animal model for evaluating its effects on hypertension.

BACKGROUND: The objectives of this study were to determine the in vitro anti-inflammatory and in vivo antihypertensive effects of fermented pepino (Solanum muricatum) milk by Lactobacillus brevis with the goal of developing functional healthy products. The inflammatory factors of fermented pepino milk with L. brevis were assessed in RAW 264.7 macrophages, including nitric oxide (NO) production. Inflammatory factor genes of cyclooxygenase (COX)-1 and -2, and tumor necrosis factor (TNF)-α were also assayed by a reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Results showed that fermented PE inhibited NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells with 150 mg mL(-1) fermented PE completely blocking LPS-induced NO production. The mRNA expressions of COX-1, COX-2, and iNOS were attenuated by treatment with higher concentrations of fermented PE (150 mg/ml). Cells treated with fermented pepino extract (PE) (100 ng mL(-1)) exhibited strikingly decreased LPS-induced expression of TNF-α mRNA. During the feeding trial, rats treated with 10% fermented pepino milk (100 µg 2.5 mL(-1)) and 100% fermented pepino milk (1000 µg 2.5 mL(-1)) exhibited significant decreases in the systolic blood pressure. CONCLUSION: Our results showed that fermented pepino milk has wide potential applications for development as a health food.