Effects of heat on the biological activity of wild Cordyceps sinensis

Background: Current methods of extending the storage time of wild Cordyceps sinensis adversely affect the nutritive and medicinal value of the product. Thus, this study was designed to investigate the effects of heat treatment, a relatively safe storage extension method, on the biological activity of wild C. sinensis. Methods: Samples were heated to 60, 80, or 100°C for 15, 30, or 60 minutes. SOD activity in wild C. sinensis before and after heating was assayed using a standard colorimetric assay. Deoxyribonuclease (DNase) activity was measured using the plasmid-nicking assay. Cordycepin content was analyzed using HPLC. Polysaccharide content was measured using the phenol-sulfuric method. The Student's t-test was used for comparison. Results: After heating at 60, 80, 100°C for 15, 30, 60 minutes, respectively, no significant reduction in DNase activity or polysaccharide dissolution was noted (P > .05). Interestingly, heating at 80°C for 30 minutes led to a significant increase in the SOD activity of C. sinensis (P  .05). Conclusions: These results suggested that heat treatment does not adversely affect SOD or DNase activity, polysaccharide content, or cordycepin dissolution. Thus, heat treatment might be a safe processing method to extend the storage time of wild C. sinensis without compromising biological activity

Hypoxic targeting and activating TH-302 loaded transcatheter arterial embolization microsphere

The tumor-derived and transcatheter arterial chemoembolization (TACE) induced hypoxia microenvironment is closely related to the poor prognosis of hepatocellular carcinoma (HCC). In this study, hypoxia-activated prodrug TH-302 loaded poly(lactic-co-glycolic acid) (PLGA)-based TACE microspheres were prepared to treat HCC through localized and sustained drug delivery. TH-302 microspheres with three different sizes were fabricated by an oil-in-water emulsion solvent evaporation method and characterized by scanning electron microscopy (SEM), infrared spectra (IR), X-ray diffractometer (XRD), and drug release profiles. The in vitro antitumor potential was firstly evaluated in an HepG2 cell model under normoxic and hypoxic conditions. Then, a VX-2 tumor-bearing rabbit model was established and performed TACE to investigate the in vivo drug tissue distribution and antitumor efficiency of TH-302 microspheres. Blood routine examination and histopathological examinations were also conducted to evaluate the safety of TH-302 microspheres. TH-302 microspheres with particle size 75–100 μm, 100–200 μm, and 200–300 μm were prepared and characterized by sphere morphology and sustained drug release up to 360 h. Compared with TH-302, the microspheres exhibited higher cytotoxicity, cell apoptosis, and cell cycle S phase retardation in HepG2 cells under hypoxic conditions. The microspheres also displayed continuous drug release in the liver tissue and better anti-tumor efficiency compared with TH-302 injection and lipiodol. Meanwhile, no serious toxicity appeared in the duration of treatment. Therefore, TH-302 microspheres showed to be feasible and effective for TACE and hold promise in the clinical for HCC chemoembolization therapy

Preparation, Pharmacokinetics, Biodistribution, Antitumor Efficacy and Safety of Lx2-32c-Containing Liposome

<div><p>Lx2-32c is a novel taxane that has been demonstrated to have robust antitumor activity against different types of tumors including several paclitaxel-resistant neoplasms. Since the delivery vehicles for taxane, which include cremophor EL, are all associated with severe toxic effects, liposome-based Lx2-32c has been developed. In the present study, the pharmacokinetics, biodistribution, antitumor efficacy and safety characteristics of liposome-based Lx2-32c were explored and compared with those of cremophor-based Lx2-32c. The results showed that liposome-based Lx2-32c displayed similar antitumor effects to cremophor-based Lx2-32c, but with significantly lower bone marrow toxicity and cardiotoxicity, especially with regard to the low ratio of hypersensitivity reaction. In comparing these two delivery modalities, targeting was superior using the Lx2-32c liposome formulation; it achieved significantly higher uptake in tumor than in bone marrow and heart. Our data thus suggested that the Lx2-32c liposome was a novel alternative formulation with comparable antitumor efficacy and a superior safety profiles to cremophor-based Lx2-32c, which might be related to the improved pharmacokinetic and biodistribution characteristics. In conclusion, the Lx2-32c liposome could be a promising alternative formulation for further development.</p></div

Mean pharmacokinetic parameters of Lx2-32c liposome and cremophor-based Lx2-32c in SD rats.

<p>Data are expressed as mean ± SD (n = 4).</p><p>AUC: Area Under Curve; MRT: Mean Retention Time; CLz/F: Clearance; Vz/F: Apparent Volume of Distribution.</p><p>Mean pharmacokinetic parameters of Lx2-32c liposome and cremophor-based Lx2-32c in SD rats.</p

Enhanced anti-hepatocarcinoma efficacy by GLUT1 targeting and cellular microenvironment-responsive PAMAM–camptothecin conjugate

<p>The efficient targeting of drugs to tumor cell and subsequent rapid drug release remain primary challenges in the development of nanomedicines for cancer therapy. Here, we constructed a glucose transporter 1 (GLUT1)-targeting and tumor cell microenvironment-sensitive drug release Glucose–PEG–PAMAM-s-s–Camptothecin-Cy7 (GPCC) conjugate to tackle the dilemma. The conjugate was characterized by a small particle size, spherical shape, and glutathione (GSH)-sensitive drug release. <i>In vitro</i> tumor targeting was explored in monolayer (2D) and multilayer tumor spheroid (3D) HepG2 cancer cell models (GLUT1⁺). The cellular uptake of GPCC was higher than that in the control groups and that in normal L02 cells (GLUT1⁻), likely due to the conjugated glucose moiety. Moreover, the GPCC conjugate exhibited stronger cytotoxicity, higher S arrest and enhanced apoptosis and necrosis rate in HepG2 cells than control groups but not L02 cells. However, the cytotoxicity of GPCC was lower than that of free CPT, which could be explained by the slower release of CPT from the GPCC compared with free CPT. Additional <i>in vivo</i> tumor targeting experiments demonstrated the superior tumor-targeting ability of the GPCC conjugate, which significantly accumulated in tumor meanwhile minimize in normal tissues compared with control groups. The GPCC conjugate showed better pharmacokinetic properties, enabling a prolonged circulation time and increased camptothecin area under the curve (AUC). These features contributed to better therapeutic efficacy and lower toxicity in H22 hepatocarcinoma tumor-bearing mice. The GLUT1-targeting, GSH-sensitive GPCC conjugate provides an efficient, safe and economic approach for tumor cell targeted drug delivery.</p

The effect of Lx2-32c liposome on WBC, RBC, PLT counts, HGB concentration and CK-MB in C57BL/6J mice.

<p>Data are expressed as means ± SD (n = 10).</p><p>*<i>p<0.05,</i> compared with that in control group;</p>#<p><i>p<0.05</i>, compared with that in Cremophor-based Lx2-32c group.</p><p>The effect of Lx2-32c liposome on WBC, RBC, PLT counts, HGB concentration and CK-MB in C57BL/6J mice.</p

Hypersensitivity reactions grading standard.

<p>Hypersensitivity reactions grading standard.</p

Characterization of the Lx2-32c liposome.

<p>A, Scanning electron microscope photograph of Lx2-32c liposome; B, The mean diameter and polydispersity index (PDI) of freshly prepared Lx2-32c liposome; C, The average zeta potential of Lx2-32c liposome.</p