The activity of polysaccharides is usually related to molecular weight. The molecular weight of polysaccharides is critical to their immunological effect in cancer therapy. Herein, the Codonopsis polysaccharides of different molecular weights were isolated using ultrafiltration membranes of 60- and 100-wDa molecular weight cut-off to determine the relationship between molecular weight and antitumor activities. First, three water-soluble polysaccharides CPPS-I (100 wDa) from Codonopsis were isolated and purified using a combination of macroporous adsorption resin chromatography and ultrafiltration. Their structural characteristics were determined through chemical derivatization, GPC, HPLC, FT–IR, and NMR techniques. In vitro experiments indicated that all Codonopsis polysaccharides exhibited significant antitumor activities, with the tumor inhibition rate in the following order: CPPS-II > CPPS-I > CPPS-III. The treatment of CPPS-II exhibited the highest inhibition rate at a high concentration among all groups, which was almost as efficient as that of the DOX·HCL (10 μg/mL) group at 125 μg/mL concentration. Notably, CPPS-II demonstrated the ability to enhance NO secretion and the antitumor ability of macrophages relative to the other two groups of polysaccharides. Finally, in vivo experiments revealed that CPPS-II increased the M1/M2 ratio in immune system regulation and that the tumor inhibition effect of CPPS-II + DOX was superior to that of DOX monotherapy, implying that CPPS-II + DOX played a synergistic role in regulating the immune system function and the direct tumor-killing ability of DOX. Therefore, CPPS-II is expected to be applied as an effective cancer treatment or adjuvant therapy.

Background: Various potential effect of drugs on alleviating diseases by regulating intestinal microbiome as well as the pharmaceutical excipients on gut microbiota has been revealed. However, the interaction between them is rarely investigated. Methods: Histological analysis, immunohistochemistry analysis, enzyme-linked immunosorbent assay (ELISA) analysis, RT-qPCR, and 16S rRNA analysis were utilized to explore the effect mechanism of the five excipients including hydroxypropyl methylcellulose (HPMC) F4M, Eudragit (EU) S100, chitosan (CT), pectin (PT), and rheum officinale polysaccharide (DHP) on berberine (BBR) to cure UC. Results: The combined BBR with PT and DHP group exhibited better therapeutic efficacy of UC with significantly increased colon length, and decreased hematoxylin-eosin (H&E) scores than other groups. Furthermore, the expression of tight junction ZO-1 and occludin in colon tissue were upregulated, and claudin-2 was downregulated. Ultimately, the serum content of tumor necrosis (TNF)-α, interleukin (IL)-1β, and IL-6 was decreased. Moreover, the combined BBR with PT significantly promoted the restoration of gut microbiota. The relative abundance of Firmicutes and Lactobacillus was significantly increased by the supplement of PT and DHP, and the relative abundance of Proteobacteria was downregulated. Conclusions: Our study may provide a new perspective that the selection of pharmaceutical excipients could be a crucial factor affecting the drugs’ therapeutic efficiency outcome.

The polyamidoamine (PAMAM) dendrimer is a highly efficient absorption promoter. In the present study, we studied the absorption-enhancing effects and the mechanism of PAMAM dendrimers with generation 0 to generation 3 (G0–G3) and concentrations (0.1–1.0%) on the pulmonary absorption of macromolecules. The absorption-enhancing mechanisms were elucidated by microarray, western blotting analysis, and PCR. Fluorescein isothiocyanate-labeled dextrans (FDs) with various molecular weights were used as model drugs of poorly absorbable drugs. The absorption-enhancing effects of PAMAM dendrimers on the pulmonary absorption of FDs were in a generation- and concentration-dependent manner. The G3 PAMAM dendrimer with high effectiveness was considered to the best absorption enhancer for improving the pulmonary absorption of FDs. G3 PAMAM dendrimers at three different concentrations were non-toxic to Calu-3 cells. Based on the consideration between efficacy and cost, the 0.1% G3 PAMAM dendrimer was selected for subsequent studies. The results showed that treatment with a 0.1% G3 PAMAM dendrimer could increase the secretion of organic cation transporters (OCTs), OCT1, OCT2, and OCT3, which might be related to the absorption-enhancing mechanisms of the pulmonary absorption of FDs. These findings suggested that PAMAM dendrimers might be potentially safe absorption enhancers for improving absorption of FDs by increasing the secretion of OCT1, OCT2, and OCT3.