A simple and sensitive LC-MS/MS method for the determination of polyphyllin VII in rat plasma and its application to pharmacokinetic study.

Polyphyllin VII is an isoprene saponin extracted from Rhizoma paridis, and it can effectively suppress tumor initiation, growth, and metastasis. In this study, we aim to develop and validate an LC-MS/MS method for the quantification of polyphyllin VII in rat plasma using digoxin as the internal standard (IS). The plasma samples were precipitated with methanol, and the samples were separated on an ACQUITY BEH C18 column (2.1 × 50 mm, 1.7 µm). The mobile phase consisted of 0.1% formic acid solution and acetonitrile. The detection was performed in the multiple reactions monitoring mode, with the precursor-to-product transitions of m/z 1075.4 > 883.3 for polyphyllin VII and m/z 779.4 > 649.6 for the IS. The method showed excellent linearity over the concentration range of 0.5-1000 ng/ml, with a correlation coefficient of 0.9996 (r = 0.9996). The lower limit of quantification was 0.5 ng/ml. The inter- and intra-day accuracy (relative error) ranged from -4.8 to 5.9%, and precision (relative standard deviation) was < 9.0%. The assay showed high extraction recovery, ranging from 90.6 to 95.6%. Polyphyllin VII was demonstrated to be stable under the storage conditions. The validated LC-MS/MS method was successfully applied to the pharmacokinetic study of polyphyllin VII in rats after oral, intraperitoneal, and intravenous administrations. The pharmacokinetic results indicated that polyphyllin VII showed low oral (5.86%) bioavailability and moderate (38.81%) intraperitoneal bioavailability.

Tackling TAMs for Cancer Immunotherapy: It's Nano Time.

The tumor microenvironment (TME) is a highly complex environment that surrounds tumors. Interactions between cancer cells/non-cancerous cells and cells/non-cell components in the TME support tumor initiation, development, and metastasis. Of the cell types in the TME, tumor-associated macrophages (TAMs) have gained attention owing to their crucial roles in supporting tumors and conferring therapy resistance. Recent developments in nanotechnology raise opportunities for the application of nano targeted drug-delivery systems (Nano-TDDS) in cancer therapy. We focus our discussion on current knowledge of TAMs, and describe recent examples of Nano-TDDS-based TAM modulation, highlighting strategies to overcome in vivo delivery barriers associated with the TME and their potential for clinical translation.

Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery.

INTRODUCTION: A reduction-sensitive CD44-positive tumor-targetable drug delivery system for doxorubicin (DOX) delivery was developed based on hyaluronic acid (HA)-grafted polymers. MATERIALS AND METHODS: HA was conjugated with folic acid (FA) via a reduction-sensitive disulfide linkage to form an amphiphilic polymer (HA-ss-FA). The chemical structure of HA-ss-FA was analyzed by ultraviolet spectroscopy, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance (NMR) spectroscopy. The molecular weight of HA-ss-FA was determined by high-performance gel permeation chromatography. Blank HA-ss-FA micelles and DOX-loaded micelles were prepared and characterized. The reduction responsibility, cellular uptake, and in vivo biodistribution of HA-ss-FA micelles were investigated. RESULTS: DOX-loaded micelles were of high encapsulation efficiency (88.09%), high drug-loading content (22.70%), appropriate mean diameter (100-120 nm), narrow size distribution, and negative zeta potential (-6.7 to -31.5 mV). The DOX release from the micelles was significantly enhanced in reduction environment compared to normal environment. The result of in vitro cytotoxicity assay indicated that the blank micelles were of low toxicity and good biocompatibility and the cell viabilities were >100% with the concentration of HA-ss-FA from 18.75 to 600.00 µg/mL. Cellular uptake and in vivo biodistribution studies showed that DOX-loaded micelles were tumor-targetable and could significantly enhance cellular uptake by CD44 receptor-mediated endocytosis, and the cellular uptake of DOX in CD44-positve A549 cells was 1.6-fold more than that in CD44-negative L02 cells. In vivo biodistribution of HA-ss-FA micelles showed that micelles were of good in vivo tumor targetability and the fluorescence of indocyanine green (ICG)-loaded micelles was 4- to 6.6-fold stronger than free ICG within 6 h in HCCLM3 tumor-bearing nude mice. CONCLUSION: HA-ss-FA is a promising nanocarrier with excellent biocompatibility, tumor targetability, and controlled drug release capability for delivery of chemotherapy drugs in cancer therapy.

Optimized Biotransformation of Icariin into Icariside II by ß-Glucosidase from Trichoderma viride Using Central Composite Design Method.

A crude ß-glucosidase has been produced from Trichoderma viride and used to explore a simple method to prepare icariside II from icariin. The crude enzyme has been studied by zymography method and used for hydrolysis of ICA. To achieve a high conversion rate of ICA, various factors have been studied including pH, reaction time, temperature, initial concentration of enzyme, and initial concentration of ICA through central composite design experiments. In the condition of the optimum hydrolysis parameters with pH 4.0, 41°C, 1.0 mg/mL ICA, and 9.8 U/mL crude ß-glucosidase, the conversion rate of ICA reached 95.03% at 1 h. Moreover, the cytotoxicity test showed that ICA II performed inhibition effects on proliferation of A549 cell, while ICA has no cytotoxicity. It indicated that the hydrolysis transformation study of ICA is valuable for exploration of active new drugs.