ABSTRACT
Background: Developing the natural medicine that allow for the specific targeting cytotoxicity is a very important research area in the development of anti-tumor drugs. Aims and Objectives: This study was conducted to determine the targeted inhibitory effects of luteolin-loaded Her-2-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on gastric cancer cells and to delineate the mechanism underlying the inhibition of tumors by luteolin. Materials and Methods: Luteolin-loaded Her-2-PLGA NPs (Her-2-NPs) were prepared, physically and chemically characterized, and their effects on gastric cancer cells were investigated. The rate of NP uptake by cells and the cell morphology were observed using confocal microscopy; the rates of cell proliferation and apoptosis were identified using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay and flow cytometry, respectively; and the mRNA and protein expression levels of forkhead box protein O1 (FOXO1) were determined using quantitative polymerase chain reaction and Western blotting, respectively. Results: Compared with nontargeted microspheres, Her-2-NPs led to significantly enhanced uptake of luteolin by SGC-7901 cells. Luteolin-loaded Her-2-NPs also significantly inhibited the proliferation of gastric cancer cells, weakened their migratory ability, and increased both the mRNA and protein expression levels of FOXO1. Conclusion: Luteolin-loading of Her-2-NPs could potentially be used as a novel anti-cancer drugs for targeted cancer therapy.
ABSTRACT
OBJECTIVE: To prepare curcumin (CUR) -Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (CUR-PLGA) thermosensitive in-situ gel (CUR-PLGA-GEL), and to study pharmacokinetic characteristics of it in aqueous humor of rabbits.METHODS: CUR-PLGA was prepared with modified emulsion-solvent evaporation method. CUR-PLGA-GEL was prepared by cold-dissolving method using poloxamer407 (P407) and poloxamer 188 (P188) as gel matrix. The level of CUR in gel was determined by HPLC, and the irritation of it to rabbit eyes was investigated (self-control of left and right eyes of 5 rabbits were taken, while the Draize test was used to evalvate the irritation). 10 New Zealand white rabbits were randomly divided into 2 groups, with 5 rabbits in each group. Left eyes were given CUR-PLGA-GEL and CUR suspension (containing CUR 8 mg), respectively. The concentrations of CUR in aqueous humor of rabbits were determined before medication and 1, 2, 4, 6, 8, 10, 12, 24 h after medication. The pharmacokinetic parameters were calculated by using DAS 2. 0 software. RESULTS: CUR-PLGA-GEL was successfully prepared and the total score of irritation was 0, which indicated irritative to rabbits. In aqueous humor of rabbits, cmax and AUC0-24 h of CUR-PLGA-GEL were 2. 48 and 2. 71 fold of CUR suspension. CONCLUSIONS: Prepared CUR-PLGA-GEL can be used for ophthalmic delivery and can improve the utilization of CUR in the eye.
ABSTRACT
The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPNs) was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles' surface with use of poly(styrene sulfonate) sodium salt (PSS) as anionic layer and poly(allylamine hydrochloride) (PAH) as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs (4 layers) exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of-57.8 mV. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles' surface could dramatically influence the drug release profile of TPNs (4 layers vs. 3 layers). In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles' surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery.
Subject(s)
Humans , Antineoplastic Agents, Phytogenic , Chemistry , Benzylisoquinolines , Chemistry , Cell Line, Tumor , Drug Liberation , Lactic Acid , Chemistry , Nanoparticles , Chemistry , Metabolism , Polyamines , Chemistry , Polyglycolic Acid , Chemistry , Polystyrenes , Chemistry , Static ElectricityABSTRACT
@#The objectives of this study were to prepare pitavastatin-loaded poly lactic-co-glycolic acid nanoparticles(PLGA), to characterize their pharmaceutical properties, to conduct in vitro drug-release from the nanoparticles, and to observe the effects on the proliferation of endothelial progenitor cells. Both pitavastatin-loaded PLGA and blank PLGA nanoparticles were prepared using emulsion-solvent diffusion method with PLGA being carrier materials. Morphology of the nanoparticles was observed by scanning electron microscopy(SEM), and particle size was analyzed by laser nanometer particle size analyzer. The drug loading and encapsulation efficiency were assayed using high-performance liquid phase. Impact of blank and pitavastatin-loaded nanoparticles on the viability of endothelial progenitor cells was investigated by CCK8 method. Pitavastatin-loaded PLGA nanoparticles exhibited the structure with spherical shape, smooth surface and average diameter of(230. 1±45)nm. The drug loading capacity and encapsulation efficiency were(10. 00±1. 83)% and(35. 54±5. 40)%, respectively. In vitro sustained-release of pitavastatin from the nanoparticles was found. The blank PLGA nanoparticles had no effect on the viability of the endothelial progenitor cells in different concentrations. Compared with pitavastatin group, pitavastatin-loaded nanoparticles(0. 01 μmol/L, 0. 1 μmol/L)had more effects on the proliferation of endothelial progenitor cells. In conclusion, emulsion-solvent diffusion method is applicable in preparation of pitavastatin-loaded PLGA nanoparticles with good shape and sustained-release of interest. Pitavastatin-loaded nanoparticles could significantly improve proliferation of the endothelial progenitor cells.