ABSTRACT
Blood-brain barrier (BBB) is the most challengeable obstacle for brain-targeted drug delivery. The combination of focused ultrasound (FUS) and microbubbles provides a new way for brain-targeted drug delivery across BBB based on the cavitation effect. This review briefly described the recent research of FUS combined with microbubbles to enhance the BBB permeability for brain-targeted drug delivery. The contents included the FUS mechanism, the types of the commercial microbubbles, shell materials, inner gas and preparation techniques of microbubbles, the opening mechanism of FUS with microbubbles, and the safety consideration. FUS combined with microbubbles may be the effective strategy to improve the BBB permeability for brain-targeted delivery, which could provide references for the clinical applications.
ABSTRACT
Curcumin( Cur) is a natural active substance extracted from the roots or tubers of traditional Chinese medicinal materials. It has anti-inflammatory and anti-tumor activities on brain diseases. Due to the poor stability,low solubility,poor absorption and low bioavailability of curcumin,N-acetyl-L-cysteine( NAC) was used as an absorption enhancer and mixed with curcumin to improve the absorption of curcumin in the body. In this paper,curcumin was smashed by airflow pulverization,and Cur-NAC mixtures were prepared by being grinded with liquid. Then,the raw material and the product were analyzed by differential scanning calorimetry( DSC),X-ray diffraction( XRD) for structural characterization. The dissolution was determined by high performance liquid chromatography( HPLC) analysis. The characteristic peaks of the samples prepared by grinding method were similar to those of the raw materials,while the melting temperature and the accumulated dissolution degree were not significantly changed. The crystal forms of the products were not changed,and no new crystal form was formed after grinding. After the administration of intranasal powder,blood samples were collected from the orbit,while the whole brain tissues were removed from the skull and dissected into 10 anatomical regions. The concentrations of curcumin in these samples were determined by UPLC-MS/MS. The concentrations of curcumin in plasma and brain were compared at different time points. After intranasal administration of two drugs,it was found that the concentration of curcumin after sniffing up the mixtures in plasma was high,and the concentration of the drug in the olfactory bulb,hippocampus,and pons was increased significantly. Within 0. 083-0. 5 h,the olfactory bulb,piriform lobe and hippocampus remained high concentrations,the endodermis,striatum,hypothalamus and midbrain reached high concentrations within 1-3 h; and the cerebellum,pons and brain extension maintained relatively high concentrations within 3-7 h. The experiment showed that nasal administration of Cur-NAC mixtures can significantly improve the bioavailability of curcumin,and lead to significant differences in brain tissue distribution.
Subject(s)
Animals , Rats , Acetylcysteine , Pharmacology , Administration, Intranasal , Biological Availability , Brain , Brain Chemistry , Chromatography, Liquid , Curcumin , Pharmacokinetics , Tandem Mass Spectrometry , Tissue DistributionABSTRACT
Objective To investigate the clinical efficacy and safety of erlotinib combined with concurrent whole brain radiotherapy (WBRT) in the treatment of multiple brain metastases from lung adenocarcinoma,and to provide objective evidence for improving the prognosis of patients.Methods Eighty-nine patients with brain metastases from epidermal growth factor receptor (EGFR)-mutant lung adenocareinoma who were admitted to our hospital were divided into experimental group (n =45) and control group (n=44) according to the different treatment methods.The experimental group received erlotinib combined with concurrent WBRT.The control group received oral administration of erlotinib alone for 28 d and then received concurrent WBRT.The survival rates were calculated using the Kaplan-Meier method and analyzed using the log-rank test.The other data were analyzed by the chi-square test.Results The objective response rate was significantly higher in the experimental group than in the control group (78％ vs.55％,P=0.000).The median progression-free survival (PFS) time in the experimental group and the control group were 9.1 months (95％ confidence interval [CI]:5.18-12.47) and 5.6 months (95％CI:3.46-9.12),respectively (P=0.078).The median overall survival (OS) time in the experimental group and the controlgroup were 14.3 months (95％CI:9.51-17.82) and 9.7 months (95％CI:4.59-16.74),respectively (P=0.032).The incidence rates of headache and dizziness were significantly higher in the experimental group than in the control group (38％ vs.14％,P=0.029;33％ vs.9％,P=0.020).Conclusions In the treatment of multiple brain metastases from EGFR-mutant lung adenocarcinoma,erlotinib combined with concurrent WBRT is superior to erlotinib alone.The combination therapy increases PFS and OS time of the nervous system in patients.
ABSTRACT
Central nervous system(CNS)diseases are serious threats to human health. Blood-brain barrier(BBB)plays an im?portant role in protecting the CNS. However,it also impedes the delivery of drugs to CNS and affects the treatment of CNS diseases. Brain targeted nano-drug delivery systems provide the possibility to brain-targeting drug delivery. In this article,we introduce the phys?iological structure and functions of BBB,and the brain targeting mechanism and the applications of brain-targeting nano-vectors to give a brief overview of the research status of brain targeting nano-drug delivery system.
ABSTRACT
Central nervous system (CNS) diseases are serious threats to human health. Blood-brain barrier (BBB) plays an important role in protecting the CNS. However, it also impedes the delivery of drugs to CNS and affects the treatment of CNS diseases. Brain targeted nano-drug delivery systems provide the possibility to brain-targeting drug delivery. In this article, we introduce the physiological structure and functions of BBB, and the brain targeting mechanism and the applications of brain-targeting nano-vectors to give a brief overview of the research status of brain targeting nano-drug delivery system.