A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer. However, its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier. Herein, we report an albumin-bound tumor redox-responsive paclitaxel prodrugs nano-delivery strategy. Using diverse linkages (thioether bond and disulfide bond), paclitaxel (PTX) was conjugated with an albumin-binding maleimide (MAL) functional group. These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles (NPs) in aqueous solution without any excipients. By immediately binding to blood circulating albumin after intravenous administration, NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates

Tumor metastasis is responsible for chemotherapeutic failure and cancer-related death. Moreover, circulating tumor cell (CTC) clusters play a pivotal role in tumor metastasis. Herein, we develop cancer-specific calcium nanoregulators to suppress the generation and circulation of CTC clusters by cancer membrane-coated digoxin (DIG) and doxorubicin (DOX) co-encapsulated PLGA nanoparticles (CPDDs). CPDDs could precisely target the homologous primary tumor cells and CTC clusters in blood and lymphatic circulation. Intriguingly, CPDDs induce the accumulation of intracellular Ca

Pure drug-assembled nanomedicines (PDANs) are currently under intensive investigation as promising nanoplatforms for cancer therapy. However, poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation. Herein, we report a core-matched nanoassembly of pyropheophorbide a (PPa) for photodynamic therapy (PDT). Pure PPa molecules are found to self-assemble into nanoparticles (NPs), and an amphiphilic PEG polymer (PPa-PEG

Prodrug nanoassemblies, which can refrain from large excipients, achieve higher drug loading and control drug release, have been placed as the priority in drug delivery system. Reasoning that glutathione (GSH) and reactive oxygen species (ROS) are highly upgraded in tumor tissues which makes them attractive targets for drug delivery system, we designed and synthetized a novel prodrug which utilized mono thioether bond as a linker to bridge linoleic acid (LA) and docetaxel (DTX). This mono thioether-linked conjugates (DTX-S-LA) could self-assemble into nanoparticles without the aid of much excipients. The mono thioether endowed the nanoparticles redox sensitivity resulting in specific release at the tumor tissue. Our studies demonstrated that the nanoassemblies had uniform particle size, high stability and fast release behavior. DTX-S-LA nanoassemblies outperformed DTX solution in pharmacokinetic profiles for it had longer circulation time and higher area under curve (AUC). Compared with DTX solution, the redox dual-responsive nanoassemblies had comparable cytotoxic activity. Besides, the antitumor efficacy was evaluated in mice bearing 4T1 xenograft. It turned out this nanoassemblies could enhance anticancer efficacy by increasing the dose because of higher tolerance. Overall, these results indicated that the redox sensitivity nanoassemblies may have a great potential to cancer therapy.

Hyaluronic acid (HA) is a natural ligand of tumor-targeted drug delivery systems (DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors (HARE and LYVE-1) are also overexpressing in the reticuloendothelial system (RES). Therefore, polyethylene glycol (PEG) modification of HA-based DDS is necessary to reduce RES capture. Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement, significantly compromising the antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform (Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage. The and investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and nonspecific biodistribution.

OBJECTIVE:To conduct screening for the active ingredients of Ziziphus jujuba with neuroprotective effect and to il-luminate their mechanisms of action preliminarily. METHODS:After neuron-like cells (PC12 cells) were respectively cultured in the ingredient of Z. jujuba with polysaccharide enriched(1 mg/ml),that with polysaccharide removed(1 mg/ml),7 kinds of flavo-noid ingredients of Z. jujuba(catechin,procyanidine B2,epicatechin,hyperoside,rutin,quercetin-3-β-D-glucoside and kaempfer-ol-3-O-rutinoside,represented by A,B,C,D,E,F,G,all at the concentrations of 3,13,30 μmol/L)and 2 kinds of nucleoside ingredients of Z. jujuba (cyclic adenosine monophosphate and cyclic guanosine monophosphate,both at the concentrations of 3, 13,30 μmol/L)for 24 h,tert-butyl hydroperoxide(tBHP,150 μmol/L)was used to act on PC12 cells for 3 h to induce oxidative cellular damage,and MTT assay was employed to detect the survival rate of PC12 cells. The PC12 cells transfected with reporter gene plasmid(pARE-Luc)were cultured as above for 24 h,luciferase(Luc)assay was used to detect the transcriptional levels of the antioxidant response element(ARE)of all groups of cells(reflected as the activity of Luc)so as to investigate the anti-injury mechanism. RESULTS:The ingredient of Z. jujuba with polysaccharide enriched could significantly increase the survival rate of PC12 cells to which oxidative damage was caused and the transcriptional level of ARE in the transfected cells. Among the flavonoid ingredients of Z. jujuba, A(30 μmol/L),B(3-30 μmol/L)and C(10-30 μmol/L)could significantly increased the survival rate of the cells,and A(30 μmol/L),B(3-30 μmol/L),C(30 μmol/L),E(30 μmol/L)and F(3-30 μmol/L)could obviously in-creased the activation level of ARE in the transfected cells. However,the nucleoside ingredients of Z. jujuba including cyclic ade-nosine monophosphate and cyclic guanosine monophosphate had no obvious effect of increasing the survival rate of PC12 cells to which oxidative damage was caused or activating the transcription of ARE in the transfected cells. CONCLUSIONS:The polysac-charide and flavonoid ingredients of Z. jujuba may be the active ingredients which account for the neuroprotective effect against oxi-dative cellular damage,and their mechanisms of action may be related to the activation of ARE transcription.

Objective To evaluate the efficacy and safety of 10-day moxifloxacin,esomeprazole plus furazolidone triple therapy as first-line treatment to eradicate Helicobacter pylori (Hp)in comparison with the 14-day quadruple therapy containing esomeprazole,amoxicillin, clarithromycin and colloidal bismuth pectin. Methods A total of 1 26 cases of endoscopically confirmed Hp-positive chronic active gastritis or peptic ulcer were randomly assigned to the treatment group to receive esomeprazole,moxifloxacin plus furazolidone triple therapy for 1 0 days;or to the control group to receive esomeprazole, amoxicillin,clarithromycin,and colloidal bismuth pectin quadruple therapy for 14 days.Clinical efficacy and safety were evaluated after 4-week treatment.Results At the end of treatment,the Hp eradication rate was 89.4%in the treatment group, and 88.3% in the control group(P>0.05).The incidence of adverse reactions in the treatment group (16.7%)was significantly lower than that in the control group (36.7%)(P<0.05).Conclusions The 10-day moxifloxacin,esomeprazole plus furazolidone triple therapy is effective and well-tolerated as first-line treatment to eradicate Hp with samilar efficacy and fewer adverse reactions compared to the 14-day bismuth-based quadruple therapy.

Objective To observe the treatment effect of joint manipulation under brachial plexus anesthesia combined with comprehensive physical therapy in treatment of periarthritis of shoulder. Mehods From 2010.3 to 2010.9, 60 patients with periarthritis of shoulder in the Department of Pain, The First People's Hospital of Jingzhou,were divided into 3 groups:group A,B and C.Twenty patients in Group A were given Joint manipulation under brachial plexus anesthesia for treatment of the periarthritis of shoulder. Twenty patients in Group B were given comprehensive physical therapy fro treatment of periarthritis of shoulder. Twenty patients in Group C were given Joint manipulation under brachial plexus anesthesia combined with comprehensive physical therapy for treatment of periarthritis of shoulder.Results All 60 patients were followed up for 1 months. At the 1st month after surgery, vas score was evaluated for patients. Postoperative and preoperative vas score difference was compared between 3 groups by t test. There was statistically significant difference in the postoperative and preoperative vas score between Group C and Group A,and between Group B and Group A (P<0.05) . Conclusion The treatment effect of Joint manipulation under brachial plexus anesthesia combined with physical therapy in treatment of periarthritis of shoulder is good, but has no obvious difference compared with comprehensive physical therapy.

Objective To observe the treatment effect of radio frequency target combined with collagenase in treatment of cervical intervertebral disc herniation. Methods From March 2011 to September 2011, 40 patients with cervical intervertebral disc herniation were divided into 2 groups: Group A and Group B. Patients in Group A were given radio frequency target radiofrequency for treatment of the cervical intervertebral disc herniation and patients in Group B of 20 were given radio frequency target combined with collagenase for treatment of cervical intervertebral disc herniation. Results 40 patients were followed up for 6 months. At the 1st week and 6 months after surgery, the VAS score difference between before and after surgery in patients were compared between two groups by t test. There was no statistically significant difference at the 1st week after surgery between two groups (P>0.05), while 6 months after surgery, there was statistically significant difference between two groups (P<0.05) .Conclusion Radio frequency target combined with collagenase for treatment of cervical intervertebral disc herniation can alleviate the pain symptoms of patients,and the short-term and long-term curative effect is very good. The long-term curative effect has statistically significant difference with pure target radiofrequency ablation treatment. Radio frequency target combined with collagenase for treatment of cervical intervertebral disc herniation has good safety, few side effects, low risks and good short-term and long-term curative effect, so it deserves to be generalized.

In this paper, chloramphenicol was selected as a model drug to prepare in situ gels. The intrinsic dissolution rate of chloramphenicol from in situ gel was evaluated using the surface dissolution imaging system. The results indicated that intrinsic dissolution rate of chloramphenicol thermosensitive in situ gel decreased significantly when the poloxamer concentration increased. The addition of the thickener reduced the intrinsic dissolution rate of chloramphenicol thermosensitive gel, wherein carbomer had the most impact. Different dilution ratios of simulated tear fluid greatly affected gel temperature, and had little influence on the intrinsic dissolution rate of chloramphenicol from the thermosensitive in situ gel. The pH of simulated tear fluid had little influence on the intrinsic dissolution rate of chloramphenicol thermosensitive in situ gel. For the pH sensitive in situ gel, the dissolution rates of chloramphenicol in weak acidic and neutral simulated tear fluids were slower than that in weak alkaline simulated tear fluid. In conclusion, the intrinsic dissolution of chloramphenicol from in situ gel was dependent on formulation and physiological factors. With advantages of small volume sample required and rapid detection, the UV imaging method can be an efficient tool for the evaluation of drug release characteristics of ophthalmic in situ gel.