ABSTRACT
The present study evaluated the protective effect of Centella asiatica (gotu kola) leaf extract (CAE) against indomethacin (IND)-induced gastric mucosal injury in rats. Gastric mucosal injury was induced by the oral administration of IND to the rats after a 24 h fast. CAE (50 or 250 mg/kg) or lansoprazole (a reference drug) was orally administrated 30 min before the IND administration, and 5 h later, the stomachs were removed to quantify the lesions. Orally administered CAE significantly reduced IND-induced gastric injury. The histopathological observations (hematoxylin-eosin and Periodic acid-Schiff staining) confirmed the protection against gastric mucosal injury. Also, CAE decreased the malondialdehyde content compared to the control group. Moreover, pretreatment with CAE resulted in a significant reduction in the elevated expression of tumor necrosis factor, Cyclooxygenase (COX)-2, and inducible nitric oxide synthase. These results suggested that CAE possesses gastroprotective effects against IND-induced gastric mucosal injury, which could be attributed to its ability to inhibit lipid peroxidation and stimulate gastric mucus secretion in the rat gastric mucosa.
Subject(s)
Centella/chemistry , Gastric Mucosa/drug effects , Indomethacin/administration & dosage , Plant Extracts/administration & dosage , Stomach Ulcer/drug therapy , Animals , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Gastric Mucosa/injuries , Gastric Mucosa/metabolism , Humans , Male , Malondialdehyde/metabolism , Plant Leaves/chemistry , Rats , Rats, Sprague-Dawley , Stomach Ulcer/chemically induced , Stomach Ulcer/genetics , Stomach Ulcer/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Advanced materials that have controllable pH-responsive properties when submerged in the lysosome have a great potential in intracellular drug delivery. We developed novel poly(L-amino acid) nanogels that were prepared by a facile cross-linking of poly[L-aspartic acid-g-(3-diethylaminopropyl)]-b-poly(ethylene glycol)-maleimide [poly(L-Asp-g-DEAP)-b-PEG-Mal] and poly(L-aspartic acid-g-ethyl thiol)-b-PEG [poly(L-Asp-SH)-b-PEG] in an oil/water emulsion condition. Interestingly, these nanogels (~125 nm in diameter) modulated volume expansion (~375 nm in diameter) in a lysosomal pH (~pH 5.0) due to an extensive proton absorption of DEAP at a low pH, which mediated lysosome swelling and the subsequent lysosome destabilization. In the in vitro tumor cell cytotoxicity test, they encouraged tumor cell death, probably owing to the leakage of lysosomal enzymes. Furthermore, encapsulating antitumor drug (e.g., doxorubicin, DOX) into these nanogels enhanced tumor cell cytotoxicity. We conclude that this nanogel system will have great potential for tumor therapy.
Subject(s)
Antineoplastic Agents/administration & dosage , Drug Carriers/chemistry , Muramidase/chemistry , Peptides/pharmacology , Animals , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/therapeutic use , Cell Line, Tumor , Cell Survival/drug effects , Doxycycline/administration & dosage , Doxycycline/therapeutic use , Drug Delivery Systems , Female , Gels , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Microscopy, Confocal , Microscopy, Fluorescence , Nanostructures , Neoplasm Transplantation , Neoplasms/drug therapy , Neoplasms/enzymology , Ovarian Neoplasms/drug therapy , Peptides/chemical synthesis , Peptides/chemistryABSTRACT
The purpose of this study was to fabricate porous poly(lactide-co-glycolide) (PLGA) microparticles for efficient pulmonary deposition and increased therapeutic duration of the antioxidant anthocyanin (ATH). These microparticles were prepared by a water-in-oil-in-water (W(1)/O/W(2)) multi-emulsion method with vaporizing ammonium bicarbonate (AB) as a porogen and starch as a viscous additive. High porosity achieved by the decomposition reaction of AB to the base of ammonia, carbon dioxide, and water vapor at 50°C enabled efficient deposition of ATH throughout the entire lung in BALB/c mice. In addition, the porous microparticles incorporating starch showed sustained ATH release characteristics (up to 5 days) and protracted antioxidant activity (up to 5 days) for 2,2-diphenyl-1-pikryl-hydrazyl (DPPH) radicals, which was comparable to that of the porous microparticles without starch which completely released ATH in 2h. Furthermore, these porous microparticles incorporating starch led to longer ATH residence (up to 20 days) in in vivo lung epithelium. We believe that this system has great pharmaceutical potential as a long-acting antioxidant for continuously relieving oxidative stress in pulmonary diseases like chronic obstructive pulmonary disease (COPD).
Subject(s)
Administration, Inhalation , Antioxidants/chemistry , Drug Carriers/chemistry , Lactic Acid/chemistry , Lung/metabolism , Polyglycolic Acid/chemistry , Animals , Anthocyanins/chemistry , Anthocyanins/therapeutic use , Antioxidants/therapeutic use , Cell Line , Drug Carriers/administration & dosage , Female , Humans , Mice , Mice, Inbred BALB C , Polylactic Acid-Polyglycolic Acid Copolymer , Porosity , Pulmonary Disease, Chronic Obstructive/drug therapyABSTRACT
Herein, we describe magnetic cell levitation models using conventional polymeric microparticles or nanoparticles as a substrate for the three-dimensional tumor cell culture. When the magnetic force originating from the ring-shaped magnets overcame the gravitational force, the magnetic field-levitated KB tumor cells adhered to the surface area of magnetic iron oxide (Fe(3)O(4))-encapsulated nano/microparticles and concentrated clusters of levitated cells, ultimately developing tumor cells to tumor spheroids. These simple cell culture models may prove useful for the screening of anticancer drugs and their formulations.
Subject(s)
Cell Culture Techniques/methods , Ferric Compounds/chemistry , Magnetics , Nanoparticles/chemistry , Cell Line, Tumor , Cell Proliferation , Cell Survival , Humans , Lactic Acid/chemistry , Microscopy, Electron, Scanning , Nanoparticles/ultrastructure , Particle Size , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Polymers/chemistryABSTRACT
A rapid and sensitive liquid chromatography-electrospray ionization tandem mass spectrometry method (LC-ESI-MS/MS) was developed and validated for the determination of goserelin in rabbit plasma. Various parameters affecting plasma sample preparation, LC separation, and MS/MS detection were investigated, and optimized conditions were identified. Acidified plasma samples were applied to Oasis((R)) HLB solid-phase extraction (SPE) cartridges. Extracted samples were evaporated under a stream of nitrogen and then reconstituted with 100microL mobile phase A. The separation was achieved on a Capcell-Pak C18 (2.0mmx150mm, 5microm, AQ type) column with a gradient elution of solvent A (0.05% acetic acid in deionized water/acetonitrile=85/15; v/v) and solvent B (acetonitrile) at a flow rate of 250microL/min. The LC-MS/MS system was equipped with an electrospray ion source operating in positive ion mode. Multiple-reaction monitoring (MRM) of the precursor-product ion transitions consisted of m/z 635.7-->m/z 607.5 for goserelin and m/z 424.0-->m/z 292.1 for cephapirin (internal standard). The proposed method was validated by assessing specificity, linearity, limit of quantification (LOQ), intra- and inter-day precision and accuracy, recovery, and stability. Linear calibration curves were obtained in the concentration range of 0.1-20ng/mL (the correlation coefficients were above 0.99). The LOQ of the method was 0.1ng/mL. Results obtained from the validation study of goserelin showed good accuracy and precision at concentrations of 0.1, 1, 5, 10, and 20ng/mL. The validated method was successfully applied to a pharmacokinetic study of goserelin after a single subcutaneous injection of 3.6mg of goserelin in healthy white rabbits.
Subject(s)
Chromatography, High Pressure Liquid/methods , Goserelin/blood , Tandem Mass Spectrometry/methods , Acetic Acid/chemistry , Animals , Cephapirin/analysis , Cephapirin/chemistry , Female , Goserelin/chemistry , Goserelin/pharmacokinetics , Linear Models , Male , Rabbits , Reproducibility of Results , Sensitivity and Specificity , Solid Phase Extraction/methodsABSTRACT
The synthesis of a chiral pilocarpine analogue 3 in which the lactone ring is replaced by an oxazolidinone and the bridging methylene group is in the ketone oxidation state has been accomplished. The utility of this compound as a key intermediate for the preparation of more complex structures was demonstrated by its reduction to two alcohol epimers and its reaction with a methylene ylide.