Anti-oxidant activity and attenuation of bladder hyperactivity by the flavonoid compound kaempferol.

OBJECTIVES: To evaluate the anti-oxidant activity of the flavonoid compound, kaempferol, and to examine its role in the suppression of oxidative stress and attenuation of bladder hyperactivity in a rat model of bladder injury. METHODS: The anti-oxidative activity of kaempferol was examined in lipopolysaccharide-treated RAW264.7 macrophages by using flow cytometry. For in vivo studies, rats were pretreated with kaempferol or vehicle for 24 h. The rat urothelium was injured by the administration of protamine sulfate for 1.5 h and irritated by the subsequent infusion of potassium chloride for 4 h. Oxidative stress in the bladder tissue was assessed using chemiluminescence assay, and the bladder pressure was determination by cystomertrogram. RESULTS: Kaempferol significantly suppressed lipopolysaccharide-induced reactive oxygen species production in RAW264.7 rat macrophages. Exposure of the rat bladder to sequential infusion of protamine sulfate and potassium chloride induced bladder hyperactivity. Pretreatment with kaempferol, prevented the formation of reactive oxygen species and prolonged the intercontraction interval. CONCLUSION: Kaempferol suppresses oxidative stress and attenuates bladder hyperactivity caused by potassium chloride after protamine sulfate-induced bladder injury.

Isotretinoin oil-based capsule formulation optimization.

The purpose of this study was to develop and optimize an isotretinoin oil-based capsule with specific dissolution pattern. A three-factor-constrained mixture design was used to prepare the systemic model formulations. The independent factors were the components of oil-based capsule including beeswax (X1), hydrogenated coconut oil (X2), and soybean oil (X3). The drug release percentages at 10, 30, 60, and 90 min were selected as responses. The effect of formulation factors including that on responses was inspected by using response surface methodology (RSM). Multiple-response optimization was performed to search for the appropriate formulation with specific release pattern. It was found that the interaction effect of these formulation factors (X1X2, X1X3, and X2X3) showed more potential influence than that of the main factors (X1, X2, and X3). An optimal predicted formulation with Y(10 min), Y(30 min), Y(60 min), and Y(90 min) release values of 12.3%, 36.7%, 73.6%, and 92.7% at X1, X2, and X3 of 5.75, 15.37, and 78.88, respectively, was developed. The new formulation was prepared and performed by the dissolution test. The similarity factor f2 was 54.8, indicating that the dissolution pattern of the new optimized formulation showed equivalence to the predicted profile.

Effect of microemulsions on transdermal delivery of citalopram: optimization studies using mixture design and response surface methodology.

The aim of this study was to evaluate the potential of microemulsions as a drug vehicle for transdermal delivery of citalopram. A computerized statistical technique of response surface methodology with mixture design was used to investigate and optimize the influence of the formulation compositions including a mixture of Brij 30/Brij 35 surfactants (at a ratio of 4:1, 20%-30%), isopropyl alcohol (20%-30%), and distilled water (40%-50%) on the properties of the drug-loaded microemulsions, including permeation rate (flux) and lag time. When microemulsions were used as a vehicle, the drug permeation rate increased significantly and the lag time shortened significantly when compared with the aqueous control of 40% isopropyl alcohol solution containing 3% citalopram, demonstrating that microemulsions are a promising vehicle for transdermal application. With regard to the pharmacokinetic parameters of citalopram, the flux required for the transdermal delivery system was about 1280 µg per hour. The microemulsions loaded with citalopram 3% and 10% showed respective flux rates of 179.6 µg/cm(2) and 513.8 µg/cm(2) per hour, indicating that the study formulation could provide effective therapeutic concentrations over a practical application area. The animal study showed that the optimized formulation (F15) containing 3% citalopram with an application area of 3.46 cm(2) is able to reach a minimum effective therapeutic concentration with no erythematous reaction.

The transport effect of submicron emulsions on 5-flurouracil topical application.

Water-in-oil submicron emulsions were used as carrier for the topical delivery of 5-fluorouracil (5FU). The effect of components such as level and hydrophilic-lipophilic balance (HLB) value of surfactant, type of cosurfactant, and drug concentration on the delivery capability of drug in the receptor fluid and in the various skin layers (stratum corneum, epidermis and dermis) were evaluated. The result showed the submicron emulsion could increase the transdermal and deposition of 5FU compared with the aqueous control. Submicron emulsion with surfactant at HLB of 6.0 had higher deposition amount of drug in epidermis layer. The deposition amount of drug in the skin layers increased with increased amounts of surfactant and drug loading of submicron emulsion. However, the 0.2% 5FU-load submicron emulsion showed a comparable deposition effect in various skin layers with the commercial product (5%, Efudix®), which indicated that the submicron emulsions could be a promising drug vehicle for topical application.

The effect of submicron emulsion systems on transdermal delivery of kaempferol.

In this study, submicron emulsions have been employed as a carrier for the topical application of kaempferol. The effect of components of submicron emulsions on the physicochemical properties and permeation capability of drug were evaluated. In case of drug-loaded submicron emulsions, the cumulative amount over 12 h (Q(12 h)), lag time and deposition in skin amount ranged from 13.0±3.4 to 236.1±21.2 µg/cm(2), 1.7 to 5.3 h, and 1.10 to 7.76 µg/cm(2), respectively, which indicated that the permeation parameters of kaempferol were markedly influenced by the component ratio. Kaempferol dispensed in isopropyl myristate was used as the control. The Q(12 h), lag time and deposition amount in skin were 4.2±1.8 µg/cm(2), 6.0 h and 2.25±0.60 µg/cm(2), respectively. The data showed that used appropriate submicron emulsions as vehicle could significantly increase the Q(12 h) and deposition amount in skin and shorten the lag time, demonstrating that submicron emulsions have a potent enhancement effect for kaempferol transdermal delivery.

Growth of CuInSe2 and In2Se3/CuInSe2 nano-heterostructures through solid state reactions.

In(2)Se(3) is an essential phase change material and CuInSe(2) is the fundamental basis of the copper-indium-gallium-diselenide (CIGS) solar energy material. In this paper, we demonstrate the feasibility to transform the phase change material to the solar energy material via the solid state reaction. The In(2)Se(3) nanobelts (NBs) were synthesized via the vapor-liquid-solid mechanism. The chemical composition and the optical properties were investigated by energy dispersive spectroscopy, X-ray photoelectron spectroscopy, and reflectance and photoluminescence spectra. In the in situ observation of the solid state reaction with Cu to form the CuInSe(2) NBs with ultrahigh vacuum transmission electron microscopy, we observed the In(2)Se(3)/CuInSe(2) transformation at atomic scale in real time. The progression of the atomic layer at the interface provided the pertinent information on the kinetic mechanism. In(2)Se(3)/CuInSe(2) nano-heterostructures were also obtained in the present investigation. The approach to the CIGS nanosolar cell was also proposed. This study shall be beneficial in the development of high-performance nanowire solar cells and nanodevices with In(2)Se(3)/CuInSe(2) nano-heterostructures.

Formulation optimization of transdermal meloxicam potassium-loaded mesomorphic phases containing ethanol, oleic acid and mixture surfactant using the statistical experimental design methodology.

Response surface methodology (RSM) was used to develop and optimize the mesomorphic phase formulation for a meloxicam transdermal dosage form. A mixture design was applied to prepare formulations which consisted of three independent variables including oleic acid (X(1)), distilled water (X(2)) and ethanol (X(3)). The flux and lag time (LT) were selected as dependent variables. The result showed that using mesomorphic phases as vehicles can significantly increase flux and shorten LT of drug. The analysis of variance showed that the permeation parameters of meloxicam from formulations were significantly influenced by the independent variables and their interactions. The X(3) (ethanol) had the greatest potential influence on the flux and LT, followed by X(1) and X(2). A new formulation was prepared according to the independent levels provided by RSM. The observed responses were in close agreement with the predicted values, demonstrating that RSM could be successfully used to optimize mesomorphic phase formulations.

Formulation optimization of estradiol microemulsion using response surface methodology.

The aim of the current study was to find an optimal estradiol-loaded microemulsion with higher permeation rate and shortened lag time (LT) for transdermal application by using a response surface methodology (RSM) and constrained mixture design. Isopropyl myristate (X1 ), distilled water (X2 ), and ethanol (X3 ) were selected as independent variables, whereas the viscosity of microemulsion and permeation parameters including the cumulative amount at 24 h (Q24h ) and LT of estradiol-loaded microemulsion through skin were set as dependent variables. The result showed that the three independent variables had a remarkable effect (p < 0.05) on the dependent variables. Moreover, the predicted and observed values of these three dependent variables of the optimal microemulsion formulations, which were produced by the RSM optimization technique, were close, demonstrating that RSM was a useful technique for optimizing pharmaceutical formulations. However, the experimental estradiol-loaded microemulsion with higher permeation rate was expected to provide effective therapeutic concentration in a workable administration area.

The effect of component of microemulsions on transdermal delivery of buspirone hydrochloride.

The aim of this study was to evaluate the influence of components such as type, level, and hydrophilic-lipophilic balance (HLB) value of surfactant, type and amount of cosurfactant, and drug concentration on the permeability of buspirone hydrochloride microemulsions through rat skin. The cumulative amount at 24 h ranged from 502.2 ± 57.8 to 1754.3 ± 616.6 µg/cm(2), flux ranged from 23.03 ± 1.84 to 83.36 ± 25.08 µg/(cm(2)/h), and lag time ranged from 3.0 to 4.7 h, indicating that the permeation parameters of buspirone from microemulsions were markedly influenced by the composition of microemulsions. In comparison with the effect of composition of microemulsions on the buspirone permeation capacity, it was found that microemulsions containing surfactant with HLB value of 11.16 possessed higher flux. The viscosity of microemulsions increased, flux decreased, and lag time was prolonged when amount of surfactant in microemulsions increased. The various cosurfactants can also influence the microemulsion formation and drug permeability. The microemulsion with ethanol as cosurfactant had higher permeation rate. However, the buspirone microemulsion with higher flux can provide the therapeutic minimum effective concentration, at workable administrated area about 3.3-5.8 cm(2), demonstrating microemulsions could be a promising drug carrier for transdermal delivery systems.

Microemulsions for intravesical delivery of gemcitabine.

The objective of this work was to develop a safe and effective delivery vehicle for topical treatment of gemcitabine. The physicochemical properties, drug release rate, drug level in plasma and bladder, and histological changes of tissue after drug administration were investigated. The electrical conductivity, mean size, and viscosity of drug-loaded microemulsions were 0.8-102.0 µS/cm, 116.8-322.5 nm, and 42.9-105.0 cps×10³, respectively. Gemcitabine loaded microemulsions showed a slower and sustained release. After intravesical administration of aqueous control and microemulsions treated, the drug concentrations in plasma were 15.11 µg/ml and 2.81-12.82 µg/ml, respectively, and the accumulation in bladder were 18.27 µg and 9.12-64.16 µg, respectively. Microemulsions slightly decreased the systemic absorption and significantly enhanced the accumulation in bladder tissue. Moreover, the preliminary toxicity studies revealed no overt adverse histological changes or tissue irritation by the microemulsion application. Therefore, the microemulsions were suggested to be a promising drug carrier for intravesical chemotherapy.

The effect of component of cream for topical delivery of hesperetin.

The aim of this study was to optimize hesperetin cream formulations by in vitro permeation study and evaluate topical whitening active effect and skin irritation by in vivo study. The results showed that the solubility of lipophilic compound of hesperetin was increased by short-chain alcohol including ethanol, glycerin, propylene glycol and polyethylene glycols 400 (PEG 400). PEG 400 showed strongest solubilized effect by increased 3400-fold. With the addition of 5% enhancers, it was found that menthol showed the most potent enhancing effect, followed by azone and depigmentation agents (linoleic acid and lecithin). Moreover, enhancers could shorten the lag time from 3.7 to 1 h. Combination of menthol, linoleic acid and lecithin of 2.5% had a higher permeation rate of 9.8 microg/cm(2)/h and lower lag time 1 h, therefore the formulation was selected to process the skin whitening and irritation test. The results showed that a significantly topical photoprotective effect with acceptable skin irritation was obtained after hesperetin cream topical application when compared with that of the non-treatment group, indicating that the hesperetin cream may be used as an effective whitening agent.

GaN nanowire arrays for high-output nanogenerators.

Three-fold symmetrically distributed GaN nanowire (NW) arrays have been epitaxially grown on GaN/sapphire substrates. The GaN NW possesses a triangular cross section enclosed by (0001), (2112), and (2112) planes, and the angle between the GaN NW and the substrate surface is approximately 62 degrees . The GaN NW arrays produce negative output voltage pulses when scanned by a conductive atomic force microscope in contact mode. The average of piezoelectric output voltage was about -20 mV, while 5-10% of the NWs had piezoelectric output voltages exceeding -(0.15-0.35) V. The GaN NW arrays are highly stable and highly tolerate to moisture in the atmosphere. The GaN NW arrays demonstrate an outstanding potential to be utilized for piezoelectric energy generation with a performance probably better than that of ZnO NWs.

In vitro permeation and in vivo whitening effect of topical hesperetin microemulsion delivery system.

Hesperetin is one of the flavonoids and possess anti-inflammatory, UV-protecting and antioxidant effects. Permeation issues for topical delivery systems of such effects are occasionally problematic, and in view of the fact that microemulsions are potential carriers for transdermal delivery system, the objective of this study was to design an optimal microemulsion formulation by in vitro permeation study for hesperetin topical dosage form and determine its topical photoprotective effect and skin irritation by in vivo study. The hesperetin-loaded microemulsion showed an enhanced in vitro permeation compared to the aqueous and isopropyl myristate (IPM) suspension dosage form of hesperetin. In comparison, the effect of co-surfactant on the drug permeation capacity, propylene glycol showed highest permeation rate, followed by ethanol, glycerol and polyethylene glycol (PEG 400). Sunscreen agent padimate O, as a transdermal enhancer could increase the permeation rate of hesperetin. In case of in vivo study, the hesperetin-loaded microemulsion showed significant topical whitening effect and diminished skin irritation when compared with the non-treatment group, indicating that the hesperetin microemulsion could be used as an effective whitening agent.