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Biomedical subjects

W I Higuchi

Publications and source records attributed to W I Higuchi.

At least 55 records · Page 3Linked to original sources
PubMed1995

The effect of temperature upon the permeation of polar and ionic solutes through human epidermal membrane.

The temperature dependence of in vitro permeation through human epidermal membrane (HEM) was determined for urea, mannitol, tetraethylammonium ion (TEA), and corticosterone. The effect of temperature upon HEM electrical resistance was also measured. The majority of the experiments involved measuring the permeability coefficients of a specific permeant at 27 degrees C and 39 degrees C for a given HEM sample, the electrical resistance was also measured at each temperature. Similar experiments were also conducted with a model synthetic porous membrane. The effect of temperature was quantitated as the ratio of the permeability at 39 degrees C to the permeability at 27 degrees C for each permeant. These ratios observed for HEM with urea, mannitol, and TEA as the permeants were 1.66 +/- 0.05, 1.76 +/- 0.14, and 1.71 +/- 0.11, respectively. The change in temperature was shown to have a similar effect upon the electrical conductance of the HEM samples. The observed ratio for corticosterone permeation was 4.5 +/- 0.4. The experimental ratios observed for the three polar/ionic permeants were shown to approach those obtained from the model porous membrane and differed greatly from the ratio observed for the more lipophilic corticosterone, indicating differences in the effective transport mechanism/pathway for these classes of permeants. The permeability of urea was also observed to be inversely proportional to the electrical resistance of the HEM samples; this relationship was shown to be independent of temperature over the temperature range studied. The temperature dependence data and the observed relationship between urea permeability and electrical resistance strongly support the existence of a porous permeation pathway through the HEM as an operative diffusional route for polar-ionic permeants.

Corticosterone↗
PubMed1995

Physical model for lesion formation in the presence of low levels of solution fluoride.

A quantitative physical model is presented for the formation of subsurface carious lesions in the presence of low levels of solution fluoride. Calculations using independently determined model parameters are in agreement with mineral density profiles measured in bovine enamel lesions. The proposed mechanism is controlled by fluoride in the following way: as fluoride diffuses into enamel, it is rapidly adsorbed to enamel crystallites, resulting in very low microenvironmental fluoride concentrations, so long as the crystals are not saturated with respect to fluoride adsorption. The result of this saturable adsorption is a widening band of fluoride-saturated crystals near the surface, beneath which the microenvironmental fluoride concentrations are negligible. In the saturated band, the microenvironmental fluoride concentration in the pore solution is high enough to suppress dissolution, while in the deeper, relatively fluoride free region, dissolution can occur. In addition to predicting observed mineral density profiles, the model also predicts the demarcation in solution conditions between the regime where subsurface lesion formation occurs and that where the dissolution pattern is that of surface erosion; and the lack of insensitivity of dissolution rate to hydrodynamics in the presence of low levels of fluoride, as contrasted to the square root of stirring rate dependency observed in the absence of fluoride.

Animals↗
PubMed1994

Quantitative in vivo iontophoretic studies.

An experimental methodology was developed to evaluate the physicochemical basis for in vitro-in vivo correlations in iontophoretic delivery situations. This experimental methodology can be used to quantitatively evaluate the extent of interaction between chemical permeation enhancers and iontophoresis for drug delivery. The inherent advantages of using Ag/AgCl electrodes are fully exploited to control pH and minimize depletion of permeant during prolonged periods of iontophoresis.

Animals↗
PubMed1994

A novel skeletal drug-delivery system using self-setting calcium phosphate cement. 3. Physicochemical properties and drug-release rate of bovine insulin and bovine albumin.

A novel drug-deliver device based on a self-setting bioactive cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and tested in vitro using bovine insulin and bovine albumin as model polypeptide drugs. Equimolar mixtures of the calcium phosphate powders containing bovine insulin and bovine albumin were transformed into a hydroxyapatite cement after being mixed with a dilute phosphoric acid solution. X-ray diffraction and FT-IR spectra results suggested that the raw materials transformed into lower crystallinity of hydroxyapatite as it hardened. In vitro drug release from cement pellets into a 0.1 mol/L phosphate buffer at pH 7.40 and 37 degrees C continued for more than 3 weeks. Release from the drug-loaded cements followed the Higuchi model equation.

Bone Cements↗
PubMed1994

A novel skeletal drug-delivery system using self-setting calcium phosphate cement. 4. Effects of the mixing solution volume on the drug-release rate of heterogeneous aspirin-loaded cement.

The effect of the mixing solution volume was investigated on the in vitro drug-release rate of a novel drug-delivery device based on a self-setting bioactive calcium phosphate cement containing aspirin as a model drug. Equimolar mixtures of metastable calcium phosphate powders containing various proportions (3-40 w/w %) of seed hydroxyapatite crystals transformed into hydroxyapatite after being mixed with dilute phosphoric acid. The drug release from cement pellets in vitro into a 0.1 mol/L phosphate buffer at pH 7.40 and 37 degrees C by the rotating disk method continued for more than 1 week. The drug-release rate from the cement increased with increasing volumes of mixing solution. The relationship between the liquid/powder ratio and the porosity of the cement was a straight line, indicating that the cement porosity depended on the amount of the mixing solution, but was independent of the amount of seed crystals. Drug release from the cement followed the modified Fick's law, with the rate increasing with the amount of mixing solution, since the porosity depended on the amount. The tortuosity of the cements was estimated from the modified Fick's equation, and the relationships between the drug release rate and the tortuosity of the pore in the drug-loaded cement in the plots were nonlinear. The results suggested that the drug-release rates from the cement were controlled by the drug diffusion in the pores.

Aspirin↗
PubMed1994

A novel skeletal drug delivery system using self-setting calcium phosphate cement. 2. Physicochemical properties and drug release rate of the cement-containing indomethacin.

A novel drug delivery device based on a self-setting bioactive cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and tested in vitro with indomethacin as a model drug. Equimolar mixtures of the calcium phosphate powders containing 2 and 5% of indomethacin were transformed into a hydroxyapatite after being mixed with a dilute phosphoric acid solution. X-ray diffraction and differential scanning calorimetry results suggested that indomethacin transformed into an amorphous form in the pores of the cement matrix as it hardened. In vitro drug release from cement pellets into a 0.1 mol/L phosphate buffer at pH 7.40 and 37 degrees C continued for > 3 weeks. Release from 2 and 5% drug-loaded cements followed the Higuchi model equation. The drug release profiles of 5% drug-loaded cements with different thicknesses (0.5, 1.0, and 1.5 g) overlapped up to 90% drug release, indicating that the drug concentration gradient in the pore was independent of the thickness of the cement as expected from the model equation.

Adsorption↗
PubMed1994

A novel skeletal drug delivery system using a self-setting calcium phosphate cement. 5. Drug release behavior from a heterogeneous drug-loaded cement containing an anticancer drug.

A novel drug delivery device based on a self-setting bioactive calcium phosphate cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and tested in vitro using the anticancer agent 6-mercaptopurine (6-MP) as a model compound. X-ray diffraction results suggest that equimolar mixtures of the calcium phosphate salts were transformed into hydroxyapatite after being mixed with a dilute phosphoric acid solution, even in the presence of various amounts of 6-MP powder. The inclusion of 6-MP in the reaction mixture resulted in the formation of a homogeneous drug-containing cement. Alternatively, the drug was loaded after cement formation to produce a heterogeneous drug-containing pellet. In vitro drug release from both the homogeneous and heterogeneous drug-loaded cement pellets into simulated body fluid (pH 7.25, 37.0 degrees C) was measured using the rotating-disk method. Release from the homogeneous 5% drug-loaded cements did not obey the Higuchi equation. The release rate from the heterogeneous drug-loaded cements of different thicknesses (1, 2, and 3 mm) was a function of thickness, indicating that release kinetics could be controlled by the design of the cement formulation.

Antineoplastic Agents↗
PubMed1994

A novel skeletal drug delivery system using self-setting calcium phosphate cement. 7. Effect of biological factors on indomethacin release from the cement loaded on bovine bone.

The use of self-setting bioactive calcium phosphate cement containing indomethacin as a model drug in bovine bone was investigated by means of an in vitro drug release test, mercury porosimetry, and scanning electron microscopy (SEM). Calcium phosphate cements containing 2 and 5% indomethacin after being mixed with dilute phosphoric acid were applied to defect sites and the medullary cavity of bovine bone and transformed into hydroxyapatite. The in vitro drug release from the cement loaded on the defect site into a simulated body fluid (SBF) containing 2.5 mM Ca2+ and 1.0 mM HPO4(2+) or 0.1 M phosphate buffer at pH 7.25 and 37 degrees C continued for more than 3 weeks. The release profiles of the drug-loaded cements in phosphate buffer were linear using the Higuchi plot; however, that was not the case for SBF. The drug release in SBF was much lower than that in phosphate buffer. The total pore volume of the cement after the drug release test in SBF was lower than its initial value. However, the pore size of 0.1-0.01 microns after drug release in phosphate buffer was higher than that seen in SBF. The micropore distribution results suggested that hydroxyapatite crystallized from SBF and the pore volume in the cement decreased after drug release. However, in phosphate buffer it appeared to dissolve. The SEM observations for cements loaded on the bone after drug release in phosphate buffer suggested that there was a boundary layer between the cement and natural bone, but this was not the case in SBF, where the cement bonded with the natural bone. The drug release rates from the cement-loaded bone were significantly higher than those from cement loaded on the dissolution holder. The results suggested that cement formation and drug release were affected by the presence of protein from natural bone. The drug release rates from the cement loaded on the defective bone were slower than those from the medullary cavity.

Animals↗
PubMed1994

Studies on the effects of applied voltage and duration on human epidermal membrane alteration/recovery and the resultant effects upon iontophoresis.

The effects of applied voltage and the duration of application upon human epidermal membrane (HEM) alterations and recovery were investigated. All experiments were conducted using a two-chamber diffusion cell with constant DC voltage (250-4000 mV) applied over a predetermined period, and HEM changes were monitored by measuring the electrical resistance before and after voltage termination. The key findings were that the rate of decrease in resistance was strongly dependent upon the applied voltage, the reversible recovery times were dependent upon both the magnitude and the duration of the applied field (frequently were several orders of magnitude greater than times for attaining significant resistance reduction), and reversible recovery times were much longer when lower voltages were applied for longer times to attain the same decrease in electrical resistance than for higher voltages at short times. These findings closely parallel those obtained on electrical breakdown/recovery of bilayer membranes (electroporation). The second part of this work examined the hypothesis that decreases in HEM electrical resistance induced by the applied voltage are accompanied by proportional increases in HEM permeability. A study was designed to test this hypothesis involving a four-stage protocol with HEM: passive transport, 250-mV iontophoresis, 2000-mV iontophoresis for 10 min, then back to 250-mV iontophoresis. The data obtained strongly support the view that the HEM alterations induced by the electric field result in pore formation and in the expected changes in HEM permeability.

Diffusion↗
PubMed1994

Transport of beta-estradiol in freshly excised human skin in vitro: diffusion and metabolism in each skin layer.

This paper describes an experimental and theoretical evaluation of beta-estradiol (E2) transport in post-surgery fresh human skin in vitro. Necessary auxiliary experimental methods were newly developed for these studies. The experimental fluxes of E2 and the metabolite, estrone (E1), using the dermis, stripped skin, and split-thickness skin were consistent with a model considering the human skin as a three-layer (stratum corneum, viable epidermis, and dermis) membrane with the enzyme activity mainly residing in the basal layer of the viable epidermis. The diffusion and metabolism parameters for each skin layer were determined in the overall transdermal transport of E2. Compared to fresh hairless mouse skin, fresh human skin appears more resistant to the stratum corneum diffusion of E2 and is much less capable of metabolizing E2 to E1. These in vitro results have been extrapolated to the possible in vivo human skin situation with blood vessels directly beneath the viable epidermis providing "sink" conditions a short distance from the dermo-epidermal junction. The model analysis has demonstrated that there would be less metabolism and that a much smaller amount of the transdermal metabolite (E1) would be taken up by the blood capillary due to the shorter dermis path length for permeants in vivo than in the in vitro case using dermatomed split-thickness skin.

Biological Transport↗
PubMed1994

Estimation of skin target site acyclovir concentrations following controlled (trans)dermal drug delivery in topical and systemic treatment of cutaneous HSV-1 infections in hairless mice.

The use of controlled transdermal delivery of acyclovir (ACV) in the treatment of cutaneous herpes simplex virus type 1 infections in hairless mice was investigated. Using an in vivo animal model (A. Gonsho, et al. Int. J. Pharm. 65:183-194 (1990)) made it possible to quantify both, the topical and the systemic antiviral efficacy of ACV transdermal patches as a function of the drug delivery rate of the patches. Drug delivery rates required to attain systemic efficacy were found to be higher than the rates required to attain the same magnitude of topical efficacy. The ACV concentrations in the basal cell layer of the epidermis for 50% topical efficacy and 50% systemic efficacy were estimated. The basal epidermis layer was considered to be the site of antiviral drug activity (skin target site). Systemic plasma levels were obtained from pharmacokinetic studies and were used to estimate the ACV concentration achieved systemically in the basal epidermis layer. A computational model for drug permeation across skin was employed to estimate the ACV concentration achieved topically in the basal epidermis layer. Equal topical and systemic efficacies were found to correspond to equal drug concentrations at the site of antiviral activity. The length of the effective diffusion pathway of drug molecules in the dermis prior to entering the blood circulation was assumed to be approximately equal to 1/20 of the anatomical dermis thickness because of dermis vascularization.

Acyclovir↗
PubMed1994

Hindered diffusion of polar molecules through and effective pore radii estimates of intact and ethanol treated human epidermal membrane.

The in vitro passive transport of urea, mannitol, sucrose and raffinose across intact and ethanol treated human epidermal membrane was investigated. The intent of this study was to characterize the barrier properties and permeation pathways of these membranes for polar permeants under passive conditions. Based upon the relative permeabilities of these four solutes and hindered diffusion theory, the experimental data was adequately modeled for both membrane systems according to permeation through a porous membrane. Effective pore radii estimates for intact human epidermal membrane fell between 15 A to 25 A while similar estimates fell compactly between 15 A to 20 A for ethanol treated human epidermal membrane. Similarities between the relative permeabilities of human epidermal membrane for the four permeants studied and the relative permeabilities of these same permeants through ethanol pretreated human epidermal membrane indicate that significant similarities exist between the permeation pathways for both membrane systems. The results of this study have important implications for transdermal drug delivery in general and more specifically for strategies of designing effective chemical permeation enhancement systems.

Diffusion↗
PubMed1994

Heat-treatment-induced reduction in the apparent solubility of human dental enamel.

Holcomb and Young (1980) have shown a significant increase in human dental enamel (HE) structural order resulting from heat treatment in the temperature range of from 275 to 400 degrees C. Also, previous work in our laboratory had shown dramatic decreases in the initial dissolution rates (IDRs) of both carbonated apatite (CAP) heated at similar temperatures (from 300 to 500 degrees C) and HE exposed to CO2 laser irradiation for which calculated surface temperatures were in this same range. We hypothesize that thermal treatment shifts the apparent solubility distribution profile of HE toward lower apparent solubilities, paralleling the observed increased in crystal structural order and the decrease in IDRs. Powdered HE was heated in a furnace at temperatures ranging from 150 to 500 degrees C for 24 hours. The apparent solubility distributions of both heated and unheated HE powders were measured by equilibration for 24 hours in a series of partially saturated solutions simulating various amounts of HE dissolved in a pH 4.5 dissolution medium. The apparent solubility distribution for the unheated HE showed a peak at KHAP [the ion activity product based on the Ca10(PO4)6(OH)2 stoichiometry] of 10(121.0). Heat treatment shifted the apparent solubility distribution to lower solubilities. The peak KHAP values were approximately 10(124.8) at 200 degrees C; approximately 10(127.8) at 300 degrees C; and approximately 10(-129.1) from 400 to 500 degrees C. This approximately 8 orders of magnitude decrease in KHAP for HE heated at from 400 to 500 degrees C correlates with the previously observed reduction in the IDR driving force for laser-treated HE experiencing a similar surface temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

Apatites↗
PubMed1994

Mechanochemical synthesis of bioactive material: effect of environmental conditions on the phase transformation of calcium phosphates during grinding.

The effect of environmental conditions on the crystalline transformation of metastable calcium phosphates during grinding was investigated using X-ray diffractometry and fourier transformed infrared spectroscopy. A mixture of CoA and dicalcium phosphate anhydrate (DCPA, CaHPO4) did not transform after grinding in air. On the other hand, CaO and dicalcium phosphate dihydrate (DCPD, CaHPO4 2H2O) were converted into a noncrystalline solid. Mixtures of DCPD and Ca(OH)2 transformed into low-crystallinity hydroxyapatite after grinding in air. When ground under N2, a mixture of Ca(OH)2 and DCPD did not transform into hydroxyapatite, whereas that of DCPD: Ca(OH)2: CaCO3 = 1:0.8: 0.2 did. The results of X-ray diffraction of FT-IR spectra suggested that the presence of carbon dioxide in the grinding system was necessary for transformation from metastable calcium phosphates to hydroxyapatite.

Air↗
PubMed1993

Fluorescence anisotropy studies on the interaction of the short chain n-alkanols with stratum corneum lipid liposomes (SCLL) and distearoylphosphatidylcholine (DSPC)/distearoylphosphatidic acid (DSPA) liposomes.

Previously, the action of the short chain n-alkanols (from C1 to C5) and isopropanol as possible enhancers on the transport of lipophilic and polar/ionic permeants across hairless mouse skin was investigated. In the present study, the steady-state fluorescence anisotropy was measured as a means of estimating the changes in fluidity caused by the n-alkanols at different depths in the stratum corneum lipid liposomes (SCLL). Some selected experiments with the distearoylphosphatidylcholine (DSPC)/distearoylphosphatidic acid (DSPA) liposomes were performed for relative comparisons. The effects of the n-alkanols on polarity sensitive parameters such as fluorescence lifetimes, fluorescence quantum yield ratios, and emission maxima were studied in the SCLL. The polarity of the bilayer decreased as the fluorescent probe was placed closer to the bilayer center and the n-alkanols did not alter this gradient. Assessment of the depth-dependent effects of the n-alkanols using SCLL showed that most of the significant changes in fluidity induced by the n-alkanols were observed at intermediate depths (C2-C9) and there was little or no increase in fluidity in the deep hydrophobic region close to the bilayer center. These results suggest that the short chain n-alkanols work as effective 'fluidizing' agents at the intermediate depths (C2-C9) in the bilayer.

1-Butanol↗
PubMed1993

A rapid method for the measurement of cholesterol thermodynamic activity in bile salt-lecithin-cholesterol solutions.

Earlier work from this laboratory suggested that the cholesterol (Ch) thermodynamic activity is a more meaningful measure of the degree of Ch supersaturation in human bile than the widely known cholesterol saturation index. An early version of a method for determining thermodynamic activity based on Ch uptake from bile salt (BS)-lecithin (LE) solutions into silicone polymer particles, but requiring 12-24 h for reaching equilibrium, was considered unsatisfactory because Ch nucleation and crystal formation frequently occurred within a few hours. The aim of the present work was to develop a method that would reduce equilibration times to the order of 1 h. Changing the thickness of the silicone film alone did not result in the desired reduction of equilibration times and it was soon deduced that the uptake of Ch by the silicone film from the BS-LE solution was a surface-controlled transport process involving the transport of Ch by negatively charged BS and BS-LE micelles at the interface. Three different approaches were tried to modify the silicone film to make its surface positively charged, thereby reducing and/or eliminating the presumed electrical repulsion barrier for the interfacial transport of Ch. The film was treated with different concentrations of aminopropyl methyl-dimethylsiloxane (AMDS) in cyclohexane, octadecyldimethyl-[3-(trimethoxysilyl)-propyl] ammonium chloride (ODTOP) in methanol, and octadecylamine solution in ethanol. Films treated with 1-1.5% ODTOP and 5-10% AMDS reduced the Ch equilibration times for model BS-LE solutions to < 1 h.

Bile Acids and Salts↗
PubMed1993

Comparison of three lasers on dental pulp chamber temperature change.

Previous studies have reported dental pulp chamber temperature changes using only one beam size per laser. This study was designed to evaluate the effects of beam size, wattage, and energy density on pulp chamber temperature changes of extracted human teeth for three lasers (CO 2, Argon, Nd:YAG). During laser irradiation of the outer enamel surface, a thermocouple was placed in the pulp chamber which measured and recorded the temperature changes. This was done for each combination of lasing dosimetry parameters. In all cases the recorded temperatures increased with the increase in beam size for a given energy density (J/cm 2) and wattage. Also, the recorded temperatures increased with increased energy density for a given wattage and beam size.

Dental Pulp Cavity↗