-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this work was to develop a thermo-reversible flurbiprofen liquid suppository base composed of poloxamer and
sodium alginate for the improvement of rectal bioavailability of flurbiprofen. Cyclodextrin derivatives such as α-, β-, γ-cyclodextrin
and hydroxypropyl-β-cyclodextrin (HP-β-CD) were used to enhance the aqueous solubility of flurbiprofen. The effects of HP-β-CD
and flurbiprofen on the physicochemical properties of liquid suppository were then investigated. Pharmacokinetic studies were
performed after rectal administration of flurbiprofen liquid suppositories with and without HP-β-CD or after intravenous administration
of commercial Lipfen® (flurbiprofen axetil-loaded emulsion) to rats, and their pharmcokinetic parameters were compared. HP-β-CD decreased the gelation
temperature and reinforced the gel strength and bioadhesive force of liquid suppository, while flurbiprofen was opposed to
HP-β-CD. Thermo-reversible flurbiprofen liquid suppository showed the physicochemical properties suitable for rectal administration.
The flurbiprofen liquid suppository with HP-β-CD showed significantly higher plasma levels, AUC and Cmax of flurbiprofen than those of the liquid suppository without HP-β-CD, indicating that flurbiprofen could be well absorbed
due to the enhanced solubility by formation of inclusion complex. Moreover, the flurbiprofen liquid suppository with HP-β-CD
showed an excellent bioavailability in that the AUC of flurbiprofen after its rectal administration was not significantly
different from that after intravenous administration of commercial Lipfen®. It is concluded that HP-β-CD could be a preferable solubility enhancer for the development of liquid suppository containing
poorly water-soluble drugs.
Journal of Inclusion Phenomena 04/2012; 64(3):265-272. · 1.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 5-Aminolevulinic acid (5-ALA), inducing photodynamic protoporphyrin (PpIX), is a hydrophilic molecule, resulting in leashing the capacity to cross tissue barriers like stratum corneum (SC) of skin. Here, we aimed to develop 5-ALA loaded ultradeformable liposomes (UDL) with different surface charges, and to investigate their physicochemical characteristics and capability for the skin penetration and retention of 5-ALA for topical photodynamic therapy (PDT). The effects of surface charges of UDL on in vitro permeation of 5-ALA and in vivo accumulation of 5-ALA-induced PpIX in viable skin were determined and then compared with conventional neutral liposomes (nLiposome). All UDL showed smaller particle size and better deformability than nLiposome. However, entrapment efficiency of 5-ALA was similar to each vesicle. Among vesicles, the cationic UDL (cUDL) demonstrated higher stability and permeability, and could deliver 5-ALA into deep skin tissue by topical application. Moreover, the 5-ALA loaded in cUDL was long retained, and induced more amount of PpIX in viable skin than those in other UDL and nLiposome. Considering that the conversion of 5-ALA into PpIX occurs preferentially in epidermis, these results suggested that topical delivery of 5-ALA loaded in cUDL could be an interesting proposal to optimize PDT related to 5-ALA.
European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 09/2011; 44(1-2):149-57. · 2.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Development of a successful bioresponsive drug delivery system requires exquisite engineering of the materials so that they are able to respond to signals stemming from the physiological environment. In this study we propose a new Pluronic(®) based thermogelling system containing matrix metalloproteinase-2 (MMP2) responsive peptide sequences. A novel thermosensitive multiblock co-polymer comprising an MMP2-labile octapeptide (Gly-Pro-Val-Gly-Leu-Ile-Gly-Lys) was synthesized from a Pluronic(®) triblock co-polymer. The polymer was designed to form a thermogel at body temperature and degrade in the presence of MMP overexpressed in a tumor. The synthesized polymer was a multiblock co-polymer with ∼2.5 U of Pluronic(®). The multiblock co-polymer solutions exhibited reverse thermal gelation around body temperature. The gelation temperatures of the multiblock co-polymer solutions were lower than those of the corresponding Pluronic(®) monomer at a particular concentration. The cytotoxicity of the synthesized polymer was lower compared with the monomer. The solubility of the hydrophobic anticancer drug paclitaxel was enhanced in the polymer solutions by micelle formation. The synthesized polymer was preferentially degraded in the presence of MMP. Paclitaxel release was dependent on the enzyme concentration. These findings suggest that the synthesized polymer has potential as a controlled drug delivery system due to its unique phase transition and bioresponsive behavior.
Acta biomaterialia 02/2011; 7(5):1984-92. · 3.98 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The objective of this study was to achieve an optimal formulation of dexibuprofen dry elixir (DDE) for the improvement of dissolution rate and bioavailability. To control the release rate of dexibuprofen, Eudragit(®) RS was employed on the surface of DDE resulting in coated dexibuprofen dry elixir (CDDE). Physicochemical properties of DDE and CDDE such as particle size, SEM, DSC, and contents of dexibuprofen and ethanol were characterized. Pharmacokinetic parameters of dexibuprofen were evaluated in the rats after oral administration. The DDE and CDDE were spherical particles of 12 and 19 μm, respectively. The dexibuprofen and ethanol contents in the DDE were dependent on the amount of dextrin and maintained for 90 days. The dissolution rate and bioavailability of dexibuprofen loaded in dry elixir were increased compared with those of dexibuprofen powder. Moreover, coating DDE with Eudragit(®) RS retarded the dissolution rate of dexibuprofen from DDE without reducing the bioavailability. Our results suggest that CDDE may be potential oral dosage forms to control the release and to improve the bioavailability of poorly water-soluble dexibuprofen.
International journal of pharmaceutics 02/2011; 404(1-2):301-7. · 2.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A sensitive and selective reverse-phase liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) method was developed and validated to quantify pseudoephedrine (CAS 90-82-4) in human plasma. Phenacetin was used as the internal standard (I.S.). Sample preparation was performed with a deproteinization step using acetonitrile. Pseudoephedrine and I.S. were successfully separated using gradient elution with 0.5% trifluoroacetic acid (TFA) in water and 0.5% TFA in methanol at a flow-rate of 0.2 mL/min. Detection was performed on a single quadrupole mass spectrometer by a selected ion monitoring (SIM) mode via electrospray ionization (ESI) source. The ESI source was set at positive ionization mode. The ion signals of m/z 166.3 and 180.2 were measured for the protonated molecular ions of pseudoephedrine and I.S., respectively. The lower limit of quantification (LLOQ) of pseudoephedrine in human plasma was 10 ng/mL and good linearity was observed in the range of concentrations 10-500 ng/mL (R2 = 1). The intra-day accuracy of the drug containing plasma samples was more than 97.60% with a precision of 3.99-11.82%. The inter-day accuracy was 99.36% or more, with a precision of 7.65-18.42%. By using this analytical method, the bioequivalence study of the pseudoephedrine preparation was performed and evaluated by statistical analysis of the log transformed mean ratios of pharmacokinetic parameters. All the results fulfilled the standard criteria of bioequivalence, being within the 80-125% range which is required by the Korea FDA, US FDA, and EMEA to conclude bioequivalence. Consequently, the developed reverse-phase LC-ESI-MS method was successfully applied to bioequivalence studies of pseudoephedrine in healthy male volunteers.
Arzneimittel-Forschung 01/2011; 61(5):276-81. · 0.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: When an inflammatory stimulus is given, vascular endothelial cells express various cell adhesion molecules including the vascular cell adhesion molecule (VCAM)-1. In this study, the possibility of specifically delivering anti-inflammatory drugs to activated endothelial cells by utilizing VCAM-1 as a target receptor was explored by loading celecoxib, a selective cyclooxygenase-2 inhibitor, into liposomes coupled to the Fab' fragment against VCAM-1. Anti-VCAM-1-Fab'-conjugated liposomes were prepared by forming an amide linkage between amino groups of Fab' and the carboxylic group of glutaryl-N-phosphatidylethanolamine in liposomes using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as a cross-linker in the presence of sulpho-N-hydroxysuccinimide. The coupling of Fab' to phospholipids constituting liposomes was confirmed by SDS-PAGE analysis. Under our optimized conjugation conditions, 130.0 µg Fab' was coupled to 1 µmol liposomes. Immunoblotting analysis showed that VCAM-1 protein expression could be induced by incubating human umbilical vein endothelial cells (HUVEC) with TNF-α. Confocal laser microsopy analysis revealed that Fab' conjugation to liposomes selectively increased liposomal uptake in TNF-α-pre-stimulated (VCAM-1-expressed) HUVECs, but not in cells without VCAM-1 expression. The concentration of celecoxib loaded in Fab'-conjugated liposomes was 281.1 ± 29 µg/mL, suggesting that liposomal loading also helped to overcome the limitations in celecoxib administration caused by its poor water solubility. Celecoxib loaded in Fab'-conjugated liposomes inhibited prostaglandin E₂ (PGE₂) production induced by TNF-α-pre-stimulation more efficiently than when loaded in conventional liposomes. Therefore, Fab'-conjugated liposomes served as a drug delivery system with dual functions: targeted delivery and solubilizing capacity.
Journal of Microencapsulation 01/2011; 28(3):220-7. · 1.55 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The principal aim of this study was to synthesize and characterize pH-sensitive biodegradable triblock copolymers containing a hydrophobic polyacetal segment for controlled drug delivery. Poly(ethylene glycol)-poly(ethyl glyoxylate)-poly(ethylene glycol) (PEG-PEtG-PEG) triblock copolymers with PEG molecular weights 500 (PEtG-PEG(500)) and 750 (PEtG-PEG(750)) were synthesized by PEtG end-capping with methoxy PEG via a carbamate linkage. Synthesized amphiphilic PEG-PEtG-PEG was characterized by (1)H NMR spectroscopy. Molecular weights of PEtG-PEG(500) and PEtG-PEG(750) were determined to be 2823 and 3387, respectively, by gel permeation chromatography. The polymers with a biodegradable polyacetal block underwent pH-dependent degradation via an acid-catalyzed hydrolysis. Paclitaxel (PTX)-loaded polymeric micelles were prepared by a dialysis method and the amount of PTX incorporated into the polymeric micelle formulations was 45,000 times greater than the water solubility of PTX at room temperature. The polymeric micelles prepared from the amphiphilic PEG-PEtG-PEG triblock copolymers have released the loaded PTX in a pH-dependent manner. The novel PEtG-based amphiphilic block copolymers can find applications for targeted and controlled drug delivery to the acidic environments found in tumors and intracellular compartments.
International journal of pharmaceutics 11/2010; 401(1-2):79-86. · 2.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To achieve better therapeutic efficacy and patient compliance in the treatment for Candida vaginitis, the antifungal agent amphotericin B (AmB) was formulated in a vaginal gel using Pluronic-based multiblock copolymers (MBCP-2). To increase its aqueous solubility, the drug was incorporated as its inclusion complex with hydroxypropyl-gamma-cyclodextrin (HPgammaCD). The formation of the AmB inclusion complex was characterized using different techniques including XRD, FT-IR spectrophotometry, DSC, and SEM. The sol-gel transition diagrams were determined by the inversion method at temperature intervals of 2 degrees C. Moreover, a histopathology study was performed to determine whether vaginal tissue damage was caused by repeated doses. The inclusion complex between AmB and HPgammaCD was completely formed, and the aqueous solubility of AmB was improved by the formation of the inclusion complex. The sol-gel transition diagrams showed that the aqueous solutions of MBCP-2 gelled at body temperature, and the gelation temperature of the polymer solutions was dependent on polymer concentration. In vitro drug release results indicated that MBCP-2 exhibited a sustained release of AmB in pH 7.4 and pH 9.0 buffers, whereas at pH 5.0, it presented a constant release that was completed within 3 days. There was no visible sign of inflammation or necrosis in vaginal tissues after repetitive intravaginal application. In conclusion, the thermosensitive vaginal gel might be useful in the delivery of an antifungal agent for local treatment.
European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 10/2010; 41(2):399-406. · 2.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The principal aim of this study was to develop an intravenous formulation of itraconazole (ITZ) using lipid nanoparticles based on binary mixture of liquid and solid lipids. Lipid nanoparticles were developed to provide the controlled release of ITZ as well as to improve the solubility of ITZ. Lipid nanoparticles were prepared with tristearin as a solid lipid, triolein as a liquid lipid, and a surfactant mixture of eggPC, Tween 80 and DSPE-PEG(2000). ITZ was incorporated at the concentration of 20mg/g. Lipid nanoparticles were manufactured by high-pressure homogenization method. The particle size and polydispersity index (PI) of lipid nanoparticles were below 280 nm and 0.2, respectively. Zeta potentials and incorporation efficiencies of lipid nanoparticles were around -30 mV and above 80%, respectively. Lipid nanoparticles containing 1% of liquid lipid showed the smallest particles size and the highest incorporation efficiency. Results from SEM, DSC and PXRD revealed that ITZ in lipid nanoparticles exists in an amorphous state. Release rates were increased as the amount of liquid lipid in lipid core increased, demonstrating that the release of ITZ from lipid nanoparticles could be controlled by modulation of the amount of liquid lipid in lipid core. Pharmacokinetic studies were performed after intravenous administration of lipid nanoparticles in rats at the dose of 5mg/kg. The plasma concentration of ITZ was prolonged after intravenous administration of lipid nanoparticles. It is concluded that binary lipid nanoparticles could control the release and pharmacokinetic parameters of ITZ.
International journal of pharmaceutics 09/2009; 383(1-2):209-15. · 2.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study is to develop a bioresponsive cisplatin (CDDP) delivery system with a self-assembling peptide amphiphile (PA) comprising a cell-adhesive matrix metalloproteinase-2 (MMP-2)-sensitive GTAGLIGQRGDS and a fatty acid. A biomimetic CDDP-PA gel was spontaneously formed upon incubating a mixture of CDDP and the PA for 5 h at 37 degrees C. CDDP-PA gel formation was confirmed by rheological analysis. The structure of self-assembled CDDP-PA nanofibers inside the gel was determined by transmission electron microscopy (TEM). Bioresponsive drug release from the biomimetic gel was demonstrated by in vitro MMP-2-triggered CDDP release. The MMP-2-sensitive CDDP release was dependent on the enzyme concentration in the medium. Enzymatic degradation of the CDDP-PA gel was confirmed by TEM images of the gel degraded in an MMP-2 containing medium. The MMP-2-triggered CDDP release as well as the presentation of RGDS in the gel would potentially provide a spatially and temporally controlled delivery system for targeted anticancer drug delivery.
Molecular Pharmaceutics 05/2009; 6(3):978-85. · 4.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Liposome-encapsulated streptokinase (SK) was prepared with distearoyl-phosphatidyl-ethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG(2000)). In vitro release assay demonstrated over 81% of SK was released from liposomes at 48 h, and the effect of its subconjunctival injection on the absorption rate of induced subconjunctival hemorrhage (SH) in rabbits was evaluated. After 8h of SH induction, eyes were randomly assigned to one of four subconjunctival injection groups (10 eyes each): group A: the free form of SK (1000 IU/mL); group B: liposome-encapsulated SK (1000 IU/mL); group C: 0.1 mL of liposomes; and group D: no injection. SHs were photographed at 8, 24, 48, 72, and 120 h after SH induction and their sizes were compared. Size decrease of the SH was faster in groups A and B than in groups C and D. Group B displayed significantly different absorption rates than group A at 24 and 48 h and with groups C and D at 24, 48, and 72 h, with the shortest mean elapsed time among all groups. The ocular absorption of SK was lower after the injection of the liposome-encapsulated SK than the free form. These results demonstrated that subconjunctival injection of liposome-encapsulated SK enhances the rate of SH absorption, especially in the early phases.
European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 05/2009; 72(3):546-51. · 3.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Folic acid, conjugated to poly(ethylene glycol)-distearoylphosphatidylethanolamine (folate-PEG-DSPE), was used to target emulsions of all-trans retinoic acid (ATRA) to folate receptor-overexpressing tumor cells. Two kinds of ATRA-incorporated folate-tethered emulsions (ATRA-FTE 2000/3400) were prepared using soybean oil, egg phosphatidylcholine and folate-PEG-DSPE with different PEG length. As a control, ATRA-incorporated non-tethered emulsion (ATRA-NTE) was prepared by using PEG2000-DSPE without folate instead of using folate-PEG-DSPE. The mean particle diameters of ATRA-FTE 2000/3400 were about 100-130 nm. The cellular uptake in KB cells of fluorescence-labeled ATRA-FTE 3400 was determined with HPLC (for ATRA) and confocal microscopy (for lipid emulsion). The growth inhibitory activity of ATRA was evaluated by MTT assay. The folate ligands in emulsion increased the cellular uptake of ATRA about 3-fold and 1.6-fold in ATRA-FTE 3400 and ATRA-FTE 2000, respectively. Growth inhibitory activity of ATRA-FTE 3400 in KB cells was higher than that of ATRA-NTE at the same dose. Whereas the growth inhibitory effect in MCF-7 cells of ATRA was similar between ATRA-NTE and ATRA-FTE 3400. The addition of free folate significantly reduced the uptake of ATRA regardless of the length of PEG attached to folate. Folate-tethered lipid emulsion showed effective and selective delivery to the folate receptor-abundant carcinomas, suggesting a potential for targeted delivery of anticancer agents.
European Journal of Pharmaceutics and Biopharmaceutics 04/2008; 68(3):618-25. · 4.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The bioequivalence of a test formulation (Nanopril, "test") and a reference formulation ("reference") of lisinopril (CAS 83915-83-7) was demonstrated by in vivo and in vitro tests. The in vivo bioequivalence study in 26 healthy volunteers was designed as a single dose, randomized, double-blind trial with a 2-week washout period between the doses. Prior to the in vivo study, an in vitro comparative dissolution test was performed by the paddle method following the bioequivalence guidance of the Korea Food and Drug Administration (KFDA). By the results of the dissolution test it was demonstrated from the similar and rapidly dissolving patterns of the two lisinopril tablets that the two formulations were pharmaceutically equivalent. However, the in vivo bioequivalence study was required to fully evaluate the bioequivalence of the two drug products. In the in vivo bioequivalence study, the plasma samples drawn from the volunteers were analyzed utilizing a sensitive LC-MS-MS analysis method and the bioequivalence between the two drug products was assessed by statistical analysis of the log transformed mean ratios of Cmax,AUC(0-t) and AUC(0-infinity). The mean maximum concentration (Cmax) of the test and reference were found to be 60.41 +/- 20.07 ng/mL and 61.11 +/- 19.36 ng/mL, respectively. The 90% confidence intervals (C.I.) of Cmax were in the range from 0.91 to 1.08. As for the AUC(0-t) and the AUC(0-infinity), test values were 792.73 +/- 273.41 ng x mL(-1) x h, 862.74 +/- 303.81 ng x mL(-1) x h and the reference values were 841.66 +/- 286.07 ng . mL(-1) x h, 906.97 +/- 318.72 ng x mL(-1) x h, respectively. The 90% C. I. of AUC(0-t) were 0.86 to 1.01 and of AUC(0-infinity), 0.87 to 1.02 and thus were within the 80-125% interval proposed by the FDA. In addition to the 90% C.I. of the pharmaceutical parameters, a two-way ANOVA showed no significant difference between the two formulations. Based upon these statistical analyses, it was concluded that the test formulation is bioequivalent to the reference.
Arzneimittel-Forschung 02/2008; 58(1):11-7. · 0.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A sensitive, simple, rapid, and specific liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) method was developed and validated for the identification and quantification of losartan in a small volume of human plasma. Losartan and I.S. were successfully separated on a CN column with a mobile phase of acetonitrile-0.2% formic acid solution (68:32, v/v). Detection was performed on a single quadrupole mass spectrometer by a selected ion monitoring (SIM) mode via electrospray ionization (ESI) source. The ESI source was set at positive ionization mode. The ion signal of m/z 422.79 and 194.81 were measured for losartan and I.S., respectively. The limit of detection (LOD) was 0.5 ng/mL (signal-to-noise ratio of 10.03) using only 200 μL of human plasma samples. The calibration curve was an excellent linear fit over the range of concentrations 1.0-1000 ng/mL (R2 = 0.9987) of losartan in human plasma. Consequently, all of our results fulfilled the common standard criteria of bioequivalence, 0.80 to 1.25 by the Korean and US Food and Drug Administration. In addition to the confidence intervals (C.I.) 90% of the pharmaceutical parameters, a two-way ANOVA showed no significant difference between the two formulations. This method was successfully applied to bioequivalence study of two brands of losartan potassium tablet (100 mg) formulations after a single oral administration.
Journal of Liquid Chromatography & Related Technologies 12/2007; 31(17):2643-2656. · 0.71 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To enhance the dissolution and oral absorption of poorly water-soluble itraconazole, self-emulsifying drug delivery system (SEDDS) composed of oil, surfactant and cosurfactant for oral administration of itraconazole was formulated, and its physicochemical properties and pharmacokinetic parameters of itraconazole were evaluated. Among the surfactants and oils studied, Transcutol, Pluronic L64 and tocopherol acetate were chosen that showed the maximal solubility to itraconazole. The solubility of itraconazole was further improved by the addition of hydrochloric acid. Droplet size of itraconazole emulsion was kept constant both in simulated gastric fluid without pepsin (pH 1.2) and simulated intestinal fluid (pH 6.8) throughout 120-min incubation period. Itraconazole in the SEDDS rapidly dissolved in every dissolution medium whereas the Sporanox showed different dissolution patterns during the 120-min incubation according to the dissolution media. In fasted and fed normal diet group, AUC(0-->24 h) and the mean maximum plasma level (Cmax) of itraconazole after oral administration of SEDDS in rats were comparable to those of itraconazole after oral dose of Sporanox. However, in fed lipidic diet group, AUC and Cmax after oral administration of SEDDS in rats were 3.7- and 2.8-fold higher, respectively, compared with those of Sporanox. These results demonstrate that the SEDDS of itraconazole composed of Transcutol, Pluronic L64 and tocopherol acetate greatly enhanced the bioavailability of itraconazole after the dose, particularly not influenced by food intake or not. Thus, this system may provide a useful dosage form for oral water-insoluble drug without food effect.
Journal of Controlled Release 01/2006; 110(2):332-8. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Previously we have formulated a new cationic emulsion, composed of 3beta [N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol and dioleoylphosphatidyl ethanolamine, castor oil and Tween 80, and it efficiently delivered plasmid DNA into various cancer cells with low toxicity. Chitosan is a natural cationic polysaccharide and is able to form polyelectrolyte complexes with DNA, in which the DNA is condensed and protected against nuclease degradation. Based on these facts, chitosan was used as a condensing agent to enhance the transfection efficiency of cationic emulsion-mediated gene delivery vehicle. The particle size, zeta potential and transmission electron micrographs of DNA/emulsion complexes were observed before and after condensation by chitosan. In vitro transfection efficiency of naked or precondensed DNA/emulsion (pcDNA/E) complexes was investigated in human hepatoma cells (HepG2) using flow cytometer, confocal microscope and western blot. In addition, in vivo gene transfer was also evaluated as GFP mRNA expression by reverse transcriptase-polymerase chain reaction. The size of transfection complexes was reduced after the condensation of DNA by chitosan. Moreover, when the pcDNA/E complexes were administered into the mice, the GFP mRNA expression was prolonged in liver and lung until day 6. These results suggest that the use of chitosan enhance the in vitro transfection efficiency and extend in vivo gene transfer.
Biomaterials 06/2005; 26(14):2147-56. · 7.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An improved column switching high performance liquid chromatographic (HPLC) method was developed for determination of cetirizine in human plasma. Plasma samples were prepared by liquid-liquid extraction using methylene chloride. The samples extracted were initially injected into a clean-up Capcell Pak MF C8 column and the peaks of cetirizine and internal standard were separated to an analytical C18 micro-column via column switching device. This analysis showed highly sensitive and selective results. Also, it was successfully applied to evaluate the pharmacokinetics of cetirizine in human volunteers after single oral administration.
Journal of Pharmaceutical and Biomedical Analysis 04/2005; 37(3):603-9. · 2.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of niflumic acid and its prodrug, talniflumate, in human plasma. Niflumic acid and talniflumate were eluted isocratically with methanol-water (73:27, v/v, adjusted to pH 3.5 by acetic acid) at a fl ow rate of 1 mL/min. Indomethacin was used as an internal standard. Signals were monitored by an UV detector at 288 nm. Retention times of indomethacin, niflumic acid and talniflumate were 5.9, 7.2 and 13.5 min, respectively. Calibration plots were linear over the range 50-5000 ng/mL for niflumic acid and 100-5000 ng/mL for talniflumate. The limits of quantitation were 50 ng/mL for niflumic acid and 100 ng/mL for talniflumate. The intra- and inter-day relative standard deviations (RSD) of niflumic acid and talniflumate were less than 10% and the accuracies were higher than 90%. This method is rapid, sensitive and reproducible for the determination of niflumic acid and talniflumate in human plasma.
Biomedical Chromatography 02/2005; 19(1):32-5. · 1.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cationic liposome has been studied as one of the most promising non-viral gene delivery systems. However, it has major drawbacks such as the formation of large aggregates at higher concentrations and the instability in the serum due to cationic lipid. As an alternative gene delivery system, cationic emulsion was formulated and transfection efficiency was evaluated in vitro and in vivo, in comparison with cationic liposome. Cationic emulsion was prepared with varying compositions of 3 beta [N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol), dioleoylphosphatidyl ethanolamine (DOPE), caster oil and Tween 80. Cationic liposome was prepared with DC-Chol and DOPE. The particle size of all the DNA/lipid complexes varied from 150 to 230 nm. The in vitro transfection efficiency of plasmid DNA was assessed by the expression of green fluorescent protein as a reporter. Of various formulations, cationic emulsion E2 (DC-Chol/DOPE/Castor Oil/Tween 80 = 0.3:0.3:0.3:0.15) and cationic liposome L3 (DC-Chol/DOPE = 0.6:0.3) showed improved transfection. DNA/E2 complexes exhibited higher transfection efficiencies (17.39+/-0.58%) in comparison with DNA/L3 complexes (11.47+/-0.59%). DNA/E2 complexes also showed a better physical stability and a stronger serum resistance than DNA/L3 complexes. Moreover, the cytotoxicity of DNA/E2 complexes was comparable to that of DNA/L3 complexes. When DNA/lipid complexes were intravenously administered, DNA/E2 complexes showed a prolonged circulation in blood and mRNA expression in various tissues compared with DNA/L3 complexes. These results suggest that cationic emulsion E2 could be a potential gene delivery system in clinical approaches because of enhanced in vivo gene transfer with low toxicity.
Biomaterials 01/2005; 25(27):5893-903. · 7.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A fully automated semi-microbore high performance liquid chromatographic (HPLC) method with column-switching using UV detection was developed for the determination of glimepiride from human plasma samples. Plasma sample (900 microl) was deproteinated and extracted with ethanol and acetonitrile. The extract (70 microl) was directly injected into a Capcell Pak MF Ph-1 pre-column where the primary separation occurred to remove proteins and retain drugs using a mixture of acetonitrile and 10mM phosphate buffer (pH 2.18) (20:80, v/v). The analytes were transferred from the pre-column to an intermediate column using a switching valve and then subsequently separated on an analytical column and monitored with UV detection at 228 nm. Glimepiride was eluted with retention time 34.9 min without interference of endogenous substance from plasma. The limit of quantification (LOQ) was 10 ng/ml for glimepiride. The calibration curves were linear over the concentration range of 10-400 ng/ml (r(2) = 0.9997). Moreover, inter- and intra-day precisions of the method were less than 15% and accuracies were higher than 99%. The developed method was successfully applied for the quantification of glimepiride in human plasma and was used to support a human pharmacokinetic study following a single oral administration of 2 mg glimepiride.
Journal of Chromatography B 11/2004; 810(1):143-9. · 2.89 Impact Factor
