Search PubMed⌕ Search

Biomedical subjects

W I Higuchi

Publications and source records attributed to W I Higuchi.

At least 127 records · Page 7Linked to original sources
PubMed1983

Correlation of microenvironmental drug concentration with inhibition of growth of microorganisms on surfaces.

Methodologies have been developed to study the concept of microenvironmental drug concentration (C*) near or around microorganisms. C* may be calculated from data on drug release from a depot site by using appropriate diffusion relationships. By following C* and correlating this with the minimum inhibitory concentration (CMIC), one could attempt to predict the effectiveness of an antiplaque agent. When C* is less than CMIC, growth would be expected to occur; when C* is higher than or equal to CMIC, growth would not be expected. Chlorhexidine diacetate was chosen for this study, which used a system involving microorganisms present on the surface of drug-treated hydroxyapatite pellets. CMIC, defined as the lowest concentration to inhibit bacterial growth, was determined independently and under conditions similar to those used in the C* experiments. Surface growth of adhering microorganisms (Streptococcus mutans SL1) was followed by scanning electron microscopy. The parameters used in the calculation of C* were determined independently. Diffusion coefficients of the drugs and the diffusion layer thickness were determined under conditions similar to those employed in the release rate studies. Surface growth was generally found to be inhibited whenever C* was significantly greater than CMIC, and growth occurred whenever C* was significantly smaller than CMIC. These findings demonstrate how C* may determine the action of a topically administered antimicrobial agent and how the various physical and chemical factors play roles in influencing this quantity.

Anti-Infective Agents, Local↗
PubMed1982

Theoretical and experimental studies of transport of micelle-solubilized solutes.

A physical model describing the simultaneous diffusion of free solute and micelle-solubilized solute across the aqueous boundary layer, coupled with partitioning and diffusion of free solute through a lipoidal membrane, is derived. In vitro experiments utilizing progesterone and polysorbate 80 showed excellent agreement between theoretical predictions based on independently determined parameters and experimental results. The physical model predicts that micelles can assist the transport of solubilized solute across the aqueous diffusion layer, resulting in a higher solute concentration at the membrane surface than would be predicted if micelle diffusion is neglected. At high surfactant concentrations, the aqueous diffusion layer resistance can be eliminated and the activity of the solute at the membrane can approach the bulk solute activity. This mechanism could explain observed enhanced absorption rates in vivo when both micelle solubilization occurs and the aqueous diffusion layer is an important transport barrier. The importance of determining and defining the thermodynamic activity of the diffusing solute is emphasized.

Biological Transport↗
PubMed1982

Influence of benzalkonium chloride on the dissolution rate behavior of several solid-phase preparations of cholesterol in bile acid solutions.

Cholesterol dissolution rate accelerators, such as benzalkonium chloride, function by reducing the interfacial barrier that exists between the negatively-charged bile acid micelle and the negatively-charged cholesterol surface. It has been proposed that this reaction is accomplished by the binding of the positively-charged accelerator to the negatively-charged micelle. An earlier report showed that different solid preparations of cholesterol give different dissolution rates under the same conditions and these differences can be primarily accounted for by variations in the interfacial transport constant (P). By using the rotating disk dissolution apparatus and the Levich theory it has been possible to study the dissolution behavior of different cholesterol solid phases as a function of the benzalkonium chloride concentration. It was shown that the ratios of P values for the different phases are relatively constant over the range of the accelerator concentrations. This suggests that the accelerators act primarily on the micelle to enhance dissolution rate.

Benzalkonium Compounds↗
PubMed1982

Hydration and percutaneous absorption III: Influences of stripping and scalding on hydration alteration of the permeability of hairless mouse skin to water and n-alkanols.

The influence of hydration on the permeability of stripped and scalded skins of hairless mice was investigated in vitro using water and n-alkanols as test permeants. Irrespective of pretreatment, the permeation rates of water, methanol, and ethanol were unaffected by aqueous immersion of skin sections in a diffusion cell, consistent with earlier data on unprocessed skins. The permeation rates of butanol and hexanol also were insensitive to hydration, differing from earlier studies on normal, intact skin in which both solutes' rates doubled after 10 hr of soaking. Following both pretreatments, the permeability of octanol declined over the first 5-10 hr of maceration, but remained invariant thereafter. The decline was most pronounced for the scalded skins. With untreated skin, octanol permeability initially increased and then declined before assuming a constant value. This study indicates that the barrier properties of the epidermis and dermis are not particularly sensitive to extended hydration except in the case of octanol. Scalding at 60 degrees for 60 sec rapidly hydrates the skin, altering tissue permeability to about the same extent as a 10-hr (or longer) immersion in water at 37 degrees. Octanol's unique hydration profile is explained by locating the origin of permeability decline in tissue beneath the horny exterior of the skin.

Abdomen↗
PubMed1982

Permeability of thermally damaged skin v: permeability over the course of maturation of a deep partial-thickness wound.

The permeability of eschar is an important factor governing rational approaches to topical control of burn wound sepsis. Previous work has shown the burn wound to have a highly variable permeability immediately after burning depending on the manner of burning. But the burn is also a dynamic wound and its physical state changes during the process of maturation. The present studies are an early attempt to characterize wound permeability as a function of maturation. Hairless mice were burned dorsally for 15 seconds on a metal surface maintained at 80 degree C. The time and temperature conditions were chosen to effect a deep partial-thickness to full-thickness injury on the animal. Mice were sacrificed daily post burn over a 2-week period and the permeabilities of 3H-methanol and 14C-butanol through the excised eschar were measured. Te eschar permeability coefficients were directly compared to permeability coefficients for the same compounds found with abdominal skin sections taken concurrently from each animal. It was observed that the branding initially caused a 50 per cent increase in the permeability of methanol and a 300-400 per cent increase in the permeability of maturation. Thereafter permeabilities tended to increase, gradually at first, but accelerating to a maximum which was observed at approximately 10 days. At the maximum, methanol's permeability was 20 times and butanol's 12 times their normal values. For both compounds permeability of eschar decreased past the maximum until termination of the studies at 14 days.

Administration, Topical↗
PubMed1981

Delivery of liposome membrane-associated sterols through silastic membranes.

The transport of sterols incorporated into the lecithin bilayer of small unilamellar liposomes through a model membrane was studied. A two-chamber diffusion cell containing liposomes with incorporated [4-14C)cholesterol or beta-[4-14C]sitosterol in the donor chamber and liposomes with unlabeled cholesterol in the receiver chamber was used. The permeability coefficients of the sterols through silastic rubber membranes which served as a model membrane were measured. The permeability for cholesterol incorporated into liposomes in a phosphatidyl choline/cholesterol molar ratio of 1 : 1, produced by sonication for 1 h, and subsequent centrifugation at 100 000 X g for 1 h, was 1.6 . 10(-8) cm sec-1. Dilution of the liposome suspension did not change the permeability coefficient significantly. The permeability coefficient of sitosterol incorporated into liposomes was about 4-times smaller than that of cholesterol. These results suggest that the sterols were delivered to the silastic membrane by the intact liposomes and that free solute was not involved in the transport to the membrane to a significant degree. The large differences in the permeability coefficients between cholesterol and sitosterol indicate that an aqueous interfacial barrier was crossed by the sterol during the delivery to the membrane.

Cholesterol↗
PubMed1981

Permeation of hairless mouse skin II: membrane sectioning techniques and influence on alkanol permeabilities.

The barrier properties of hairless mouse skin were examined by separating the skin into its component epidermal and dermal strata, using both mechanical and thermal techniques, and then assessing the permeability of each stratum to the homologous alkanols. The permeability data, when compared to those obtained previously for full-thickness hairless mouse skin and to new data for the permeability of the alcohols through a perfect lipid membrane, allow assignment of diffusional resistances to the respective, anatomically distinguishable membrane strata. It was found that the principal barrier for the lower alkanols is the epidermis, which contains the stratum corneum. The effective aqueous tissue resistances of the cellular and aqueous strata of full skin, the epidermis, and the dermis were estimated using sectioned skins. This resistance was much greater than that of an equivalent thickness of water. These data and methods represent a novel approach in the permeation analysis of a biological tissue and offer a means of estimating the effects of skin damage on percutaneous absorption.

Alcohols↗
PubMed1981

Dissolution rate behavior of solid cholesterol preparations in bile acid solutions.

Recent work in these laboratories showed that different preparations of cholesterol monohydrate and anhydrous cholesterol had different dissolution rates under the same conditions. A method was developed by which both the thermodynamic contribution (Cs) and the interfacial kinetic contribution (P) to dissolution could be determined from experimental data. The rotating-disk dissolution method was used with the Levich theory to assess the data. Dissolution rates were determined in solutions partially saturated with cholesterol. Dynamic solubilities were determined by plotting dissolution rates (J/A) versus bulk concentration (Cb) and extrapolating to zero J/A. By using a best-fit analysis, it was possible to determine solubility as well as the interfacial transport constant independently. When this method was used to study differences in dissolution behavior of different solid preparations of cholesterol the differences could be accounted for primarily by variations in the interfacial transport constant rather than by solubility variations.

Benzoates↗
PubMed1981

Variability in dissolution rates of cholesterol pellets in bile acid solutions.

Large variations in dissolution rate behavior of cholesterol monohydrate pellets may result from small changes in experimental procedures. For example, when cholesterol monohydrate pellets were stored overnight prior to a dissolution run, the initial dissolution rates varied by more than a factor of 2. It is well known that cholesterol monohydrate is converted to anhydrous cholesterol; cholesterol may be unstable toward light. heat, and other radiation in the presence of air, leading to its decomposition. To determine the cause of the variable dissolution rates, experiments were conducted with pellets "aged" under various conditions. The data shown that the probable cause of the variations is the pellet surface conversion of the monohydrate to anhydrous cholesterol, which may take place during pellet storage. The combined effects of temperature and humidity seem to be important. A uniform experimental procedure is needed if investigators hope to reproduce results within their own laboratories as well as reproduce the findings of others.

Bile Acids and Salts↗
PubMed1981

Fluoride remineralization of demineralized bovine tooth enamel and hydroxyapatite pellets.

Both bovine enamel and hydroxyapatite pellets were remineralized in a fluoride-containing remineralization solution after prior demineralization for various lengths of time. In both the enamel and pellet systems, the degree of remineralization attainable was directly related to the extent of prior demineralization, although the demineralized material was never 100% recovered in remineralization. In some cases, fluoride levels up to several thousand parts per million were found at depths as great as 50 micrometers from the surface. The stoichiometry of the remineralized material and electron microprobe examination were consistent with the formation of fluoridated hydroxyapatite rather than calcium fluoride.

Animals↗
PubMed1981

Novel topical fluoride delivery system I: remineralization of ground bovine teeth.

Laboratory studies were carried out on a newly conceived fluoride-containing remineralizing system with bovine teeth. The prototype fluoride delivery device involved micronized calcium fluoride maintained at the tooth surface with a cellulose film. Together with salivary calcium and phosphate (or simulated saliva), this system was able to generate and maintain the appropriate thermodynamic activity driving force for significant fluorapatite deposition in a reasonably short time (approximately 48 hr).

Animals↗
PubMed1981

Novel topical fluoride delivery system II: remineralization of human teeth.

A recently conceived calcium fluoride-containing remineralization system was tested using human teeth in vitro. The influence of several variables (surface pretreatment, demineralization time, and remineralization time) was studied. Appreciable levels of fluoride taken up by pumiced human teeth were found at depths up to 50 micrometers when remineralization was carried out in either the remineralizing solution or saliva. The successful performance of the delivery device in these laboratory studies is encouraging and indicates that the logical evolution of the crude devices studied thus far could lead to clinically practical fluoride delivery devices.

Fluorides↗
PubMed1980

Physical model evaluation of topical prodrug delivery--simultaneous transport and bioconversion of vidarabine-5'-valerate III: Permeability differences of vidarabine and n-pentanol in components of hairless mouse skin.

The permeation behavior of 3H-vidarabine (3H-9-beta-D-ara-binofuranosyladenine) and 14C-n-pentanol through different strata of hairless mouse skin was studied using a diffusion cell at 37 degrees under steady-state conditions. Partition coefficients for the skin components verus 0.9% aqueous NaCl solution also were obtained. Various skin preparations including full-thickness skin, cellophane-stripped skin, and dermis membranes of different thicknesses were employed. The dermis membranes were considered to be diffusionally homogenous, and the product of the permeability coefficient and the thickness was taken as the apparent diffusivity. The apparent diffusivities for both compounds investigated were independent of thickness. Therefore, it was concluded that the molecular diffusivity is constant throughout the dermis. Comparisons of permeability coefficients in various strata of the skin revealed that, while the stratum corneum is the major diffusional barrier, the epidermis appears to be significantly less permeable than the dermis.

Administration, Topical↗
PubMed1980

Physical model evaluation of topical prodrug delivery--simultaneous transport and bioconversion of vidarabine-5'-valerate IV: Distribution of esterase and deaminase enzymes in hairless mouse skin.

A semiquantitative assessment of estrase and deaminase distributions in hairless mouse skin was performed in vitro. The enzyme activities were quantified using 3H-vidarabine and tis 5'-valerate as the substrates. Full-thickness skin of the hairless mouse was cut into two halves, and each half was homogenized in pH 7.4 buffer. BQOTH THE SUPERNATE AND THE RESIDUE OF THE HOMOGENATE were assayed for esterase and deaminase activities. Results show that the outer half-thickness of the skin contained more esterase but slightly less deaminase than the other half. The characteristics of the esterase and the deaminase reactions also were studied employing the crude enzyme extract; these reactions were essentially irreversible. The deaminase reaction was in the linear region of Michaelis-Menten kinetics for substrate concentrations up to 4.5 x 10(-5) M.

Aminohydrolases↗