ABSTRACT
Lipoic acid (LA), an endogenous small molecule in organisms, has been extensively used for the highly efficient clinical treatment of malignant diseases, which include diabetes, Alzheimer's disease, and cancer over the past seven decades. Tremendous progresses have been made on the use of LA in nanomedicine for the development of various biomaterials because of its unique biological properties and highly adaptable structure since the first discovery. However, there are few reviews thus far, to our knowledge, summarizing this hot subject of research of LA and its derived biomaterials. For this purpose, we present herein the first comprehensive summary on the design and development of LA and its derived materials for biomedical applications. This review first discusses the therapeutic use of LA followed by the description of synthesis and preclinical study of LA-derived-small molecules. The applications of various LA and poly (lipoic acid) (PLA)-derived-biomaterials are next summarized in detail with an emphasis on the use of LA for the design of biomaterials and the diverse properties. This review describes the development of LA from a clinical therapeutic agent to a building unit of various biomaterials field, which will promote the further discovery of new therapeutic uses of LA as therapeutic agents and facile development of LA-based derivates with greater performance for biomedical applications.
Subject(s)
Alzheimer Disease , Neoplasms , Thioctic Acid , Humans , Thioctic Acid/therapeutic use , Thioctic Acid/chemistry , Biocompatible Materials/therapeutic use , Antioxidants/therapeutic use , Alzheimer Disease/drug therapy , Neoplasms/drug therapy , Polyesters/therapeutic useABSTRACT
Successful hepatocellular carcinoma (HCC) therapy in vivo remains a significant challenge due to the down-regulated expression of the receptors on the surface of tumor cells for compromised active targeting efficiency and cellular uptake of nanoparticles (NPs)-based drug delivery systems (DDSs) and "accelerated blood clearance" and premature unpackaging of NPs in vivo induced by the poly(ethylene glycol)ylation (PEGylation). Inspired by the repeatedly highlighted prolonged blood circulation property of RBCm-camouflaged NPs, we hypothesis that the prolonged blood circulation property resulting from RBCm coating outperforms the active targeting mechanisms of various targeting ligands for enhanced HCC therapy in vivo. Clarification of this hypothesis is therefore of great significance and urgency to break the afore mentioned bottlenecks that hamper the efficient HCC treatment in vivo. For this purpose, we reported in this study the first identification of a determining factor of nanocarriers for enhanced HCC therapy in vivo by the use of the previously fabricated pectin-doxorubicin nanoparticles (PDC-NPs) as a typical example, i.e., the natural RBCm was used as a stealth coating of PDC-NPs for the fabrication of biomimetic DDSs, PDC@RBC-NPs via hypotonic dialysis and mechanical co-extrusion methods. Comprehensive in vitro and in vivo evaluation and comparison of the properties and performance of PDC@RBC-NPs and PDC-NPs were performed in terms of colloidal stability, biosafety, drug release profiles, macrophage escape, anti-HCC effect. The resulting PDC@RBC-NPs outperformed PDC-NPs for HCC therapy in vitro and in vivo. Notably, PDC@RBC-NPs-treated BALB/c nude mice showed a significantly smaller final average tumor volume of 613 mm3 after 16 days than the PDC-NPs-treated group with an average value of 957 mm3. Therefore, the PDC@RBC-NPs developed herein showed great potential for clinical transformations due to the facile preparation and superior therapeutic efficiency against HCC. Most importantly, prolonged blood circulation was identified as a determining factor of nanocarriers instead of active targeting for enhanced HCC therapy in vivo, which could be used to direct the future design and development of advanced DDSs with greater therapeutic efficiency for HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Nanoparticles , Animals , Carcinoma, Hepatocellular/pathology , Doxorubicin , Liver Neoplasms/metabolism , Mice , Mice, Nude , Renal DialysisABSTRACT
To observe metabolic abnormalities, histology changes and eNOS expression of aorta in type 2 diabetes rat.And to observe intervention effect of rosiglitazone.Methods 80 male Wistar rats were randomized to control group, high diet group, diabetes group, and rosiglitazone treatment group (diabetes plus rosiglitazone treatment).Type 2 diabetes models were developed and rosiglization group was treated with rosiglitazone .Six weeks and twelve weeks after treatment with rosiglitazone, blood glucose, endothlin and nitric oxide were tested.Histology changes of aorta in different groups were observed under microscopy .Meanwhile the protein and mRNA expression of eNOS in aorta were examined.Results 1)Compared with control group, ET in high fat diet group, diabetes group and rosiglitazone group increased significantly , and the level of NO decreased significantly at 6 week and 12 week.At 12 week, ET in diabetes group increased, and NO decreased significantly than that of high fat diet group and rosiglitazone group.2)Histology changes were observed in high fat diet group , diabetes group and rosiglitazone group at 12 week.3)Compared with control group, protein and mRNA expression in high fat diet group , diabetes group and rosiglitazone group were down regulated at 6 week and 12 week.And protein expression in diabetes group was down regulated than that in rosiglitazone group .Conclusions Rosiglization can ease the endothelial dysfunction in type 2 diabetes rat.
ABSTRACT
Objective:To explore clinical application effect of cardiac remote real -time monitoring system.Methods:Cardiac remote real -time monitoring warning instrument(iHolter)was applied in 210 patients.The iHolter gave a-lerts automatically in case of ECG abnormalities for corresponding treatment in time,and it offered corresponding reports on monitoring results.According to age,patients were divided into youth group(<45 years,n=59),mid-dle-aged group(45160 years,n=56)and aged group(≥60 years,n=95).Characteristics of arrhythmias among different age and sex were analyzed.Results:ECG abnormalities were found in 191 cases(90.95%)out of 210 pa-tients,including eight cases with malignant arrhythmias,in which five cases were treated and survived after timely intervention via alerts.Compared with youth group and middle -aged group,there were significant rise in percenta-ges of paroxysmal atrial tachycardia(16.9%,26.8% vs.54.7%)and atrial fibrillation(0%,0% vs.8.4%)in aged group,P< 0.05 or <0.01;abnormal percentages of heart rate variability of middle -aged group and aged group were significantly higher than that of youth group(25.0%,36.8% vs.5.1%,P<0.01 both).Male percent-age of paroxysmal ventricular tachycardia was significantly higher than that of female(81.3% vs.18.8%,P=0.013).Conclusion:Cardiac remote real-time monitoring system can offer timely alerts for cardiovascular events such as arrhythmia and myocardial ischemia etc.,fight for more time for rescuing patients,maximally protect cardi-ac function and improve accuracy of clinical diagnosis.