Narrow Results

This study was designed to determine the antinociceptive effect and related neuronal mechanism of electroacupuncture (EA) on paclitaxel (PTX)-induced neuropathic pain in mice. PTX (4 mg/kg, i.p.) was administered once a day for 5 consecutive days to induce neuropathic pain. EA stimulation (2 mA, 2 Hz, 30 min) was applied at the ST36 acupoint bilaterally once in every 2 days. Repeated EA stimulation significantly attenuated PTX-induced mechanical allodynia and thermal hyperalgesia. In a separate set of experiment, the antinociceptive effect of a single EA stimulation 8 days after PTX treatment was reduced by intrathecal pretreatment with naloxone (opioid receptor antagonist), idazoxan (alpha2-adrenoceptor antagonist) or propranolol (beta-adrenoceptor antagonist), but not prazosin (alpha1-adrenoceptor antagonist). Moreover, EA remarkably suppressed the PTX-enhanced phosphorylation of the NMDA receptor NR2B subunit in the spinal dorsal horn, and intrathecal pretreatment of naloxone, idazoxan (IDA) or propranolol blocked the effect of EA. In conclusion, EA stimulation at the ST36 acupoint significantly diminished PTX-induced neuropathic pain in mice via the mediation of spinal opioid receptor, alpha2- and beta-adrenoceptors.

Millipore's HEScGRO Medium Advances Human Embryonic Stem Cell Research.

A TCM Specialist — Beijing Tongrentang Co Ltd.

Diagnostics Firm Adaltis to Acquire Shanghai Hua Tai Biotechnology.

Organon Acquires Stake in HUYA to Develop Chinese Biopharmaceuticals.

Renhuang Pharmaceuticals Received Major Order from Anhui Huayuan Pharmaceutical.

Sinovac Biotech Ltd—A Leading Chinese Biotech Company.

Skystar Bio-Pharmaceutical Signs Letter of Intent for Joint Scientific Research Project with TNI-Penta.

Boston Scientific's Reports on Major Adverse Events of TAXUS Stent Study in Diabetic Patients.

AsiaPharm Acquires Nanjing-based Pharmaceutical Group.

DSM Biologics and Crucell Announced Licensing Agreement with AbGenomics Corporation.

Grant Life Sciences Signs Collaboration Agreement with Taiwan's UCL for Diagnostic Products Validation.

ScinoPharm Launches More Cancer Treatment APIs.

Using molecular dynamics simulation method, the effects of external electric fields of 900MHz and 2450 frequencies on $\alpha \beta$-tubulin dimer stabilized by paclitaxel, have been modeled. Due to this purpose, two systems, (A) $\alpha \beta$-tubulin dimer and (B) $\alpha \beta$-tubulin dimer stabilized by paclitaxel, were exposed to an external electric field of 0.01V/nm with frequency values of 900MHz and 2450MHz. It was found that application of these fields, which are in the range of cell phone and microwave frequencies, increased the flexibility of each system. Since paclitaxel, as chemotherapy drug, is used to increase the rigidity of dimer, application of such fields may disturb the effect of paclitaxel on the dimer. Consequently, negative side effects on the chemotherapy process may be observed.

Chemotherapy for metastatic gastric cancer surely has a survival benefit compared to best supportive care. In the recent decades, some phase III trials have been conducted for metastatic gastric cancer all over the world. However, no chemotherapy regimen has shown a survival benefit with 5-FU alone, and there is no standard treatment. Recently, not a few anti-tumor agents have been developed, including irinotecan, oral pyrimidines, Taxane, and molecular target agents. Many phase I and II trials conducted in Asia have shown their activity both as single agents and in combination. Moreover, phase III trials including these new agents are underway, and some of them are expected to prolong survival and establish a standard treatment for metastatic gastric cancer.

Synthesis of pyropheophorbide-a-paclitaxel (PPa-PTX) conjugate was performed in high yield with the aim of searching for an optimal agent for cancer treatment. After synthesis, the conjugate was confirmed to be linked through an ester bond at the 2′ position of the paclitaxel moiety using multi-nuclear magnetic resonance spectroscopy. Phototoxicity of PPa and PPa-PTX conjugate, as well as PTX, was evaluated with three human cancer cell lines (HeLa, CaSki and TC-1). The new conjugate at 0.01–0.06 μM displayed 20–40% higher phototoxicity in HeLa and CaSki cell lines than free PPa and PTX. Furthermore, cellular uptake of these bio-molecules was examined by confocal laser scanning microscopy. Although PPa-PTX showed a delayed uptake compared to PPa, it penetrated completely into cells within 24 h incubation.

Paclitaxel (PTX) is usual for the treatment of a variety of malignancies, however, its applications are greatly limited due to its poor water solubility. Over the past years, there has been a considerable research interest in the area of nanoscale drug delivery systems (DDSs) as carrier for PTX due to their solubilization, safety, targeting and controlled release. There are many different types and shapes of nanoscale DDSs that have been prepared to deliver PTX, including nanoliposome, lipid nanoemulsion, nanosuspension, nanocapsule, nanofiber, nanotube, nanopolymersome, micelle and nanoparticle (NP). Nanoscale DDSs can be based on lipids, proteins, polysaccharides, polymers or other materials. The recent strategic developments of PTX formulation have been discussed with emphasis on lipid-, polymer- and protein-based nanoscale DDSs. Here we focus on the comparative analysis of the preparation, morphology, solubilization, targeting, penetrability, controllability and efficacy profile of various PTX-loaded nanoscale DDSs, which were reported in the different researches. Meanwhile the advantages and disadvantages are also discussed for each type of DDS. Furthermore, the current review embodies an in-depth discussion of human serum albumin (HSA) NP formulation, which showed significantly great efficacy and low toxicity. All the information obtained in this review might shed light on designing new and better nanoscale PTX formulations for potential anticancer applications in the clinic.

Chemotherapy has been proven to be an efficient strategy for the treatment of prostate cancer (PC). However, the insufficient cellular uptake of drugs is the biggest challenge for PC therapy. Therefore, in order to address the above concern, we developed tumor-targeted hyaluronic acid-silver nanoparticles (HA-Ag NPs), in which hyaluronic acid can specially bind with its receptor CD44 overexpressed on LNCaP cells. HA-Ag NPs have been used to load paclitaxel (PTX) to prepare functionalized silver nanoparticles (HA-Ag-PTX). The average particle size of HA-Ag-PTX was about 70 nm and kept under 120 nm for eight days. androgen-sensitive prostate cancer cells (LNCaP) cells show good uptake of HA-Ag-PTX, and HA-Ag-PTX enters LNCaP cells in a clathrin-mediated energy-dependent manner. HA-Ag-PTX exhibits an excellent pH response release of PTX under the acidic condition, which is beneficial to enhance the distribution of PTX in the tumor microenvironment. HA-Ag-PTX effectively suppresses the migration and proliferation of LNCaP cells probably by arresting the cellular cycle at $G$0/$G$1 phase and enhancing the production of the reactive oxygen species. It is worth mentioning that HA-Ag-PTX exhibits greater anticancer activity in comparison with free PTX in the LNCaP cell model, indicating that HA-Ag NPs can effectively enhance the anticancer efficacy of PTX. As a whole, these findings suggest that HA-Ag-PTX has promising potential for PC therapy.

Mesoporous silica, as a drug carrier, has become the new research focus in the field of nanodrug delivery system in recent years. In this study, Mn-doped mesoporous silicas are synthesized by template and in-situ doping method and physically characterized. The drug-loading performance of silica and its impact on drug release are studied. The Mn-doped mesoporous silicas show dendritic morphology (MDMS) with a loose wrinkle structure on the surface and a large number of pores. MDMS is used as a carrier to solve the problem of low water solubility of paclitaxel. In order to avoid leakage during drug transportation, the surface of Mn-doped mesoporous silica loaded with paclitaxel is coated with N-succinyl chitosan to construct a new type of nanodrug delivery system (MDMS-PTX-NSC). Compared to MDMS, MDMS-PTX-NSC shows an increase in particle size and smooth surface. The dissolution characteristics of manganese ions and swelling behavior of N-succinyl chitosan make MDMS-PTX-NSC delivery system exhibit a good pH-responsive release. And MDMS-PTX-NSC release curve can be well fitted by Ritger-Peppas equation. The cytotoxicity test shows that the MDMS-PTX-NSC has significant biocompatibility and enhanced cytotoxicity, which reveals that the MDMS-PTX-NSC is a promising nanodrug delivery system.

Castration-resistant prostate cancer (CRPC) and its metastases are the main reasons for the high mortality of prostate cancer. Currently, paclitaxel (PTX)-based chemotherapeutics are used as first-line drugs to treat CRPC, but this treatment does not show good effects and is accompanied by serious side effects, which may be because intravenously injected chemotherapeutic drugs have difficulties gathering at the tumor site. Therefore, a safe and effective drug delivery carrier is urgently needed to enhance the therapeutic effects of chemotherapeutic drugs against CRPC. Methoxy polyethylene glycol-polylacticco-glycolic acid-polylysine (mPEG-PLGA-PLL) nanoparticles (NPs) have shown high drug encapsulation efficiency and good therapeutic effects against ovarian cancer and pancreatic cancer, but there are few studies on their treatment against CRPC. To expand the applications of mPEG-PLGA-PLL NPs, in this study, mPEG-PLGA-PLL NPs loaded with PTX (PTX-NPs) were synthesized. The synthesized PTX-NPs had a uniform particle size and no obvious aggregation. PTX-NPs can be uptaked by PC-3 cells, which significantly promotes the inhibition of proliferation and apoptosis effects of PTX on cells and reduces the expression levels of CDK6, Cyclin D1 and Bcl-2 (cyclins and an apoptosis inhibitor), and these effects can be further enhanced by ultrasound-induced microbubble cavitation (UIMC). Our research provides a new nanocarrier for the treatment of CRPC, laying the foundation for further research in the future.

Bioartificial biodegradable materials were prepared mixing chitosan (CHI) and poly(vinyl alcohol) (PVA), then manufactured as films, and finally cross-linked with glutaraldehyde (GTA), both in the absence and in the presence of the edible hexa-alcohol sorbitol (SOR), as a plasticizer. The release of the components into water was tested by high performance liquid chromatography (HPLC); no release of CHI and scarce release of PVA were found. The water uptake was tested by measuring the swelling of the materials, after incubating them for 20 h in an atmosphere saturated with water vapor at 37°C. The swelling percentage increases with increasing CHI content in the blends, although it is the less hydrophilic polymer. This behavior was attributed to the difficulty of water to diffuse through the crystalline PVA structure, which is partially altered in the blends. The addition of SOR enhances the water sorption, as expected. The biodegradability of the materials was tested using the specific enzyme chitosanase, and was found to depend on the blend composition, as well as to be enhanced by the addition of SOR. The initial degradation rates were calculated; the maximum rates were found when the CHI to PVA ratio was 80:20 for all systems. The results of the enzymatic degradation generally agree with those of the swelling. The cross-linked blends were also tested as drug-delivery systems. The drugs chosen were the vitamin L-ascorbic acid (AsA) and the anti-cancer drug paclitaxel (PTX). The effective diffusion coefficients, Deff, were evaluated for the release of both the drugs from each material. Those of AsA are greater, of many powers of ten, than those of PTX, owing mainly to the hydrophilic nature of the first drug and to the hydrophobic of the second one. In conclusion, these materials seem available for biomedical use.

Trastuzumab (anti-HER2 monoclonal antibody) possesses significant clinical activity in breast cancer, and attracts attention as a candidate for molecular target therapy. Furthermore, it was reported that the combination of trastuzumab and paclitaxel improves the anti-tumor effect for metastatic breast cancer. To further understand the molecular basis of trastuzumab and/or paclitaxel in breast cancer therapy, we have visualized these molecules in vivo using quantum dot (Qdot) and GFP. Qdot is relatively new fluorescent dye with longer fluorescent bleaching time and strong fluorescent. We found that trastuzumab blocked HER2 recycling and inhibited the growth of breast cancer cell. Paclitaxel inhibited microtubule depolymerization and mitosis, which induced cell death. Furthermore, the microtubule network which is essential for intracellular transport was fragmented by the combination of trastuzumab and paclitaxel, resulted in the inhibition of intracellular transports. Compared to the individual effect of trastuzumab or paclitaxel, the combination of these two drugs were more effective in inducing cell death in the HER2-overexpressing breast cancer cell.