Objective To prepare quercetin (QT)-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (QPTN) and QT-loaded polylactic-co-glycolic acid (PLGA) nanoparticles (QPN) by using QT as model drug and PLGA-TPGS or PLGA as carrier materials, and to investigate the quality of the two nanoparticles. Methods QPTN and QPN were prepared by using the ultrasonic emulsification-solvent evaporation method, and their surface morphology,size and surface charge were detected by using a transmission electron microscope (TEM) and a Nano ZS90 light scattering and laser Doppler anemometry, respectively. Drug loading (DL), entrapment efficiency (EE) and in vitro drug release of QT in the two nanoparticles were determined by using a reverse phase-high performance liquid chromatography (RP-HPLC) on Hypersil C18 column (4.6 mm×250 mm, 5 μm) with methanol and 0.03% phosphoric acid (3:2) as mobile phase, and the detective wavelength was 370 nm. Results TEM images exhibited that two nanoparticles were all spherical and regular. The average sizes of QPTN and QPN were (155.4±2.7) nm and (363.8±3.2) nm, while DL and EE of QPTN were approximately (21.6±2.8)%, (93.7±2.9)% (n=6), and DL and EE of QPN were approximately (15.0±1.5)%, (64.6±1.6)% (n=6), respectively. Both of nanoparticles exhibited sustained release, and the cumulative QT release of QPTN and QPN reached (85.8±2.8)% and (68.6±1.4)% (n=6) at day 30, respectively, with a significant difference between them (P<0.05). Conclusion QPTN gets smaller size, higher DL and EE, and exhibits sustained release, and the in vitro cumulative QT release is faster and more complete than QPN relatively.
DAJASF.Life or death:neuroprotective and anticancer eff-ects of quercetin[J].J Ethnopharmacology,2012,143(2):383-396.
Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Quercetin is a ubiquitous flavonoid that is present in numerous plants that are utilized in many different cultures for their nervous system and anticancer effects. To better understand the neuroprotective and antiproliferative activities of quercetin, we present a comprehensive review of the divergent actions that contribute to the ethnopharmacological profile of these plants. RESULTS: The pharmacological activities of quercetin that modulate antioxidation/oxidation/kinase-signaling pathways might be differentially elicited in neurons compared with malignant cells, ultimately promoting cell survival or death in a cell type- and metabolism-specific manner. Whereas the broad antioxidation and anti-inflammatory activities of quercetin are important for neuronal survival, the oxidative, kinase- and cell cycle-inhibitory, apoptosis-inducing effects of quercetin are essential for its anticancer effects. The diverse mechanistic interactions and activities of quercetin that modulate the phosphorylation state of molecules as well as gene expression would alter the interconnected and concerted intracellular signaling equilibrium, either inhibiting or strengthening survival signals. These mechanisms, which have been mainly observed in in vitro studies, cannot be easily translated into an explanation of the divergent simultaneous neuroprotective and anticancer effects observed in vivo. This is in part due to low bioavailability in plasma and in the brain, as well as the nature of the actual active molecules. CONCLUSIONS: Numerous studies have demonstrated the beneficial effects of chronic quercetin intake, which is ethnopharmacologically meaningful, as many plants that are chronically ingested by people contain quercetin. Although quercetin and quercetin-containing plants exhibit potential as therapeutic modalities in neuropathology and in cancer, the data collectively highlight the need to elucidate issues such as bioavailability as well as its correlation with effectiveness at biomarkers in vivo. There would be an increased potentential of these plants for chemoprevention and neuropathology prevention. Copyright 脗漏 2012 Elsevier Ireland Ltd. All rights reserved.
Abstract Quercetin can inhibit the growth of cancer cells with the ability to act as a 'chemopreventer'. Its cancer-preventive effect has been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis, as well as its antioxidant functions. Quercetin can also reduce adipogenesis. Previous studies have shown that quercetin has potent inhibitory effects on animal fatty acid synthase (FASN). In the present study, activity of quercetin was evaluated in human liver cancer HepG2 cells. Intracellular FASN activity was calculated by measuring the absorption of NADPH via a spectrophotometer. MTT assay was used to test the cell viability, immunoblot analysis was performed to detect FASN expression levels and the apoptotic effect was detected by Hoechst 33258 staining. In the present study, it was found that quercetin could induce apoptosis in human liver cancer HepG2 cells with overexpression of FASN. This apoptosis was accompanied by the reduction of intracellular FASN activity and could be rescued by 25 or 50 脦录M exogenous palmitic acids, the final product of FASN-catalyzed synthesis. These results suggested that the apoptosis induced by quercetin was via the inhibition of FASN. These findings suggested that quercetin may be useful for preventing human liver cancer.
Quercetin is the most abundant flavonoid in human diet. It has special interest as it holds anticancerous properties. This study aims to clarify the mechanisms involved in quercetin effects during the occurrence of preneoplastic lesions in rat liver.Methods and resultsAdult male Wistar rats were subjected to a two-phase model of hepatocarcinogenesis (initiated-promoted group). Initiated-promoted animals also received quercetin 10 and 20 mg/kg body weight (IPQ10 and IPQ20 groups, respectively). Antioxidant defenses were modified by quercetin administration at both doses. However, only IPQ20 group showed a reduction in number and volume of preneoplastic lesions. This group showed increased apoptosis and a reduction in the proliferative index. In addition, IPQ20 group displayed a reduction of cell percentages in G1 and S phases, accumulation in G2, and decrease in M phase, with reduced expression of cyclin D1, cyclin A, cyclin B, and cyclin-dependent kinase 1. Interestingly, peroxisome proliferator activated receptor- levels were reduced in IPQ20 group.ConclusionThe outcomes of this study represent a significant contribution to the current understanding on the preventive mechanisms of quercetin during the early stages of liver cancer development, demonstrating that in addition to its known proapoptotic characteristics, the flavonoid modulates the expression of critical cell cycle regulators and peroxisome proliferator activated receptor- activity.
JAIN RA.The manufacturing techniques of various drug loaded biodegradable poly (lactide-co-glycolide) (PLGA) devices[J].Biomaterials,2000,21(23):2475-2490.
A considerable research has been conducted on drug delivery by biodegradable polymeric devices, following the entry of bioresorbable surgical sutures in the market about two decades ago. Amongst the different classes of biodegradable polymers, the thermoplastic aliphatic poly(esters) like poly(lactide) (PLA), poly(glycolide) (PGA), and especially the copolymer of lactide and glycolide, poly(lactide-co-glycolide) (PLGA) have generated immense interest due to their favorable properties such as good biocompatibility, biodegradability, and mechanical strength. Also, they are easy to formulate into different devices for carrying a variety of drug classes such as vaccines, peptides, proteins, and micromolecules. Also, they have been approved by the Food and Drug Administration (FDA) for drug delivery. This review discusses the various traditional and novel techniques (such as in situ microencapsulation) of preparing various drug loaded PLGA devices, with emphasis on preparing microparticles. Also, certain issues about other related biodegradable polyesters are discussed.
GUOY,LUOJ,TANS,et al.The applications of vitamin E TPGS in drug delivery[J].Eur J Pharm Sci,2013,49(2):175-186.
Abstract D-伪-Tocopheryl polyethylene glycol 1000 succinate (simply TPGS or Vitamin E TPGS) is formed by the esterification of Vitamin E succinate with polyethylene glycol 1000. As novel nonionic surfactant, it exhibits amphipathic properties and can form stable micelles in aqueous vehicles at concentration as low as 0.02 wt%. It has been widely investigated for its emulsifying, dispersing, gelling, and solubilizing effects on poorly water-soluble drugs. It can also act as a P-glycoprotein (P-gp) inhibitor and has been served as an excipient for overcoming multidrug resistance (MDR) and for increasing the oral bioavailability of many anticancer drugs. Since TPGS has been approved by FDA as a safe pharmaceutic adjuvant, many TPGS-based drug delivery systems (DDS) have been developed. In this review, we discuss TPGS properties as a P-gp inhibitor, solubilizer/absorption and permeation enhancer in drug delivery and TPGS-related formulations such as nanocrystals, nanosuspensions, tablets/solid dispersions, adjuvant in vaccine systems, nutrition supplement, plasticizer of film, anticancer reagent and so on. This review will greatly impact and bring out new insights in the use of TPGS in DDS. Copyright 漏 2013 Elsevier B.V. All rights reserved.
BAOX,GAOM,XUH,et al.A novel oleanolic acid- load-ed PLGA-TPGS nanoparticle for liver cancer treatment[J].Drug Devel Indust Pharm,2015,41(7):1193-1203.
Hepatocellular carcinoma is the third most common cause of cancer death. Oleanolic acid (OA) is a natural triterpenoid, has many important biological actions, including antitumor effect, but its poor solubility often leads to poor pharmacodynamics. The aim of our work is to make OA-loaded poly (lactide-co-glycolide)-d-伪-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (OPTN) to improve its efficacy to liver cancer and characterize it. OPTN were prepared by ultrasonic emulsification-solvent evaporation technique using PLGA with or without the addition of TPGS (OPN). The coumarin-6-loaded nanoparticles were used as a fluorescence marker. The nanoparticles were characterized for surface morphology, surface charge, particle size, drug loading, encapsulation efficiency, in vitro drug-release, cellular uptake, cytotoxicity by human liver cancer cell line HepG2 cells, and therapeutic effect in vivo. The prepared nanoparticles were found to be spherical in shape. The in vitro drug-release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake and cytotoxicity of OPTN in the HepG2 cells compared with that of OPN. The treatment of OPTN group was better than OPN and FS groups in vivo. The results showed advantages of OPTN in terms of sustainable release and efficacy in liver cancer chemotherapy compared with OPN. OPTN could be acted as a novel and new dosage form to be used in cancer treatment study.
LIUH,GAOM,XUH,et al.A promising emodin-loaded poly (lactic-co-glycolic acid)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy[J].Pharm Res,2016,33(1):217-236.
Emodin (EMO) has multi-targets and multi-way antitumor effect, which was limited by the instability and poor solubility of EMO. The aim of this study was to formulate EMO-loaded poly (lactide-co-glycolide)-d-伪-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (EPTN) to increase the liver targeting of EMO for cancer therapy.EMO/coumarin-6-loaded PLGA-TPGS nanoparticles (ECPTN) and EMO-loaded PLGA nanoparticles (EPN) were also prepared as comparison. The cellular uptake of ECPTN by HepG2 and HCa-F cells was investigated using Confocal laser scanning microscopy. The apoptosis of HepG2 cells handled with EPTN was assayed by flow cytometry. The liver targeting property of ECPTN in mice was evaluated using the drug concentration determined by RP-HPLC and the freezing slices were investigated via fluorescence inversion microscopy. The blood samples were obtained from vein intubation to illustrate the pharmacokinetics process of EPTN. The tumor-bearing mice model was established to elucidate the in vivo therapeutic effect of EPTN.The results demonstrated that ECPTN could be internalized by HepG2 and HCa-F cells respectively. The ratio of apoptosis cells was increased after dealing with EPTN. The detection indexes of drug concentration and fluorescence inversion microscopy images indicated ECPTN had an excellent effect on liver targeting property than EMO solutions (EMS). The pharmacokinetics process of EPTN showed obvious sustained-release effect than EMS. Compared with EPN, the in vivo antitumor activity of EPTN against tumor cells were better.In conclusion, EPTN could be used in the treatment of liver cancer acted as a kind of promising intravenous dosage forms.
, 张成鸿
