[Thermosensitive gel of polysaccharide from Ganoderma applanatum combined with paclitaxel for mice with 4T1 breast cancer].

Polysaccharide from Ganoderma applanatum has the activities of anti-tumor and enhancing immune function. There were no reports on antitumor effect of its intratumoral injection. In this study, the polysaccharide was extracted from G. applanatum by water extraction and alcohol precipitation, and purified by ceramic membrane after removing protein by Sevage method. The total polysaccharide content from G. applanatum(PGA)was about 63%. The combination of PGA and paclitaxel showed synergistic effect on cytotoxicity of 4 T1 cells at lower concentrations in vitro. In addition, the growth curve of 4 T1 cells showed that PGA could retard the growth of 4 T1 cells gradually. The PGA thermosensitive gel(PGA-TG)was prepared by using poloxamer 188 and 407. The gel temperature was 36 ℃, and the PGA-TG could effectively slow down the release rate of PGA in vitro. 4 T1 breast cancer-bearing mice were used as a model to evaluate the therapeutic effect of intratumoral injection of PGA combined with tail vein injection of nanoparticle albumin-bound paclitaxel(nab-PTX). In high and low dose PGA groups, each mice was given with 2.25, 1.125 mg PGA respectively, twice in total, and the dosage of paclitaxel was 15 mg·kg~(-1), once every 3 days, for a total of five times. The tumor inhibition rate was 29.65% in the high dose PGA-TG group, 58.58% in the nab-PTX group, 63.37% in low dose PGA-TG combined with nab-PTX group, and 68.10% in high dose PGA-TG combined with nab-PTX group respectively. The inhibitory effect in high dose PGA-TG group combined with nab-PTX on tumors was significantly higher than that in nab-PTX group(P<0.05). The results showed that paclitaxel therapy combined with intratumoral injection of PGA-TG could improve the therapeutic effect for 4 T1 mice and reduce the side effects of chemotherapy.

Effects of ß-Cyclodextrin and Hydroxypropyl-ß-Cyclodextrin Inclusions on the Degradation of Magnolol by Intestinal Bacteria.

Cyclodextrin (CD) inclusions are generally used to increase the solubility of poorly soluble drugs. In this study, magnolol (MAG) was used as a model drug for exploring the effects of CD on the degradation of pharmaceutical drugs by intestinal microflora. MAG/ß-cyclodextrin (ß-CD) and MAG/hydroxypropyl-ß-CD (HP-ß-CD) inclusion complexes were successfully prepared by the saturated aqueous solution and freeze-drying methods, respectively. Structural characterisation along with analyses of solubility, residual water content and drug content of the inclusion complexes was performed. The intestinal microflora of male rats was used to study MAG degradation in vitro. At three concentrations, the degradation of both the inclusion complexes was slower than that of the MAG monomer, MAG and CD mixtures and the MAG-poloxamer 188 micelle. There were no statistically significant differences in the degradation of the MAG/ß-CD and MAG/HP-ß-CD inclusion complexes. A simulation first-order equation of the degradation parameters revealed that the degradation of the inclusion complexes was slower and pronounced, judging by slope. The experimental findings were verified by molecular docking for predicting the stable molecular structure of the inclusion complexes. In conclusion, the inclusion complexes partially protected MAG from degradation by the intestinal bacteria.

Modified mixed nanomicelles with collagen peptides enhanced oral absorption of Cucurbitacin B: preparation and evaluation.

Polymer nanoparticles modified with collagen peptides (CPs) are an attractive strategy for the oral delivery of active ingredients from Chinese medicine. Thus, in the present study, collagen cationic CPs were simply separated using ion-exchange resin from bovine CPs, to modify mixed nanomicelles (MMs) on the surface to improve the oral bioavailability of Cucurbitacin B (CuB). The physicochemical property of micelles was characterized, which confirmed the successful modification of the nanomicelles. CPs-modified nanomicelles in vitro were found to significantly increase cellular uptake and transportation. Compared to unmodified micelles, the quantity of CPs-modified micelles internalized by Caco-2 cells were 3.74 times greater and the cumulative transportation flux (AP-BL) was 2.81 times greater. The membrane transportation process of CuB-MMs-CPs was found to be associated with energy consumption and clathrin- and caveolin-mediated endocytosis. In vivo studies performed on rats indicated that in comparison to CuB and CuB-MMs, the relative bioavailability of CuB-MMs-CPs increased by 3.43 times and 2.14 times, respectively. In addition, the tumor inhibition caused by CuB-MMs-CPs was increased significantly. Therefore, the nanomicelles co-modified with isolated CPs could act as attractive carriers for oral delivery of CuB.