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Biomedical subjects

Joseph Kost

Publications and source records attributed to Joseph Kost.

10 recordsLinked to original sources
PubMed2005

On-demand release by ultrasound from osmotically swollen hydrophobic matrices.

Ethylene-vinyl acetate copolymer (EVAc) based controlled release systems are composed of a continuous hydrophobic polymer phase and of dispersed solid drug particles. In matrices with high drug loadings (> or =50%) most drug particles are interconnected. Thus, when these matrices are immersed in water, release rates are relatively high. In matrices with low drug loadings (<40%) most drug particles are isolated within the continuous hydrophobic polymer matrix. Thus, release rates are very low. Matrices containing water soluble particles at a low loading swell intensely after immersion in water; this is caused by the osmotic force of the isolated particles which causes the water to permeate into the hydrophobic polymer. The enclosed drug particles absorb water, and at the end of the swelling process the matrices consist of an immense number of fluid pockets containing dissolved drugs. In attempt to develop on-demand release systems, we studied the effect of ultrasound (US) on the release rates of these swollen matrices. We found that low-frequency ultrasound (20 kHz) reversibly increased the release rates from these swollen matrices by a factor of 30-500, in contrast to the unswollen matrices, where the release rates increased only by a factor of 2-3. Unswollen and swollen matrices react differently to US, as unswollen matrices contain drug particles which absorb ultrasound on the surface of the matrices, causing ultrasound attenuation. On the other hand, swollen matrices contain a compact arrangement of fluid pockets separated from each other by thin membranes containing a solution of the dissolved drug, therefore ultrasound penetrates through the matrix volume. Ultrasound penetration causes tearing of these membranes within the matrices. As a result, the fluid pockets interconnect, and drug molecules diffuse out through these interconnected pockets.

Drug Carriers↗
PubMed2005

The nature of ultrasound-SLS synergism during enhanced transdermal transport.

Ultrasound and sodium lauryl sulfate (SLS) exhibit a synergistic effect on transdermal transport, when applied simultaneously on the skin. The synergistic mechanism is not fully understood. Previous studies have shown that application of ultrasound simultaneously with SLS, results in enhanced mass transfer and improved penetration and dispersion of the surfactant. In this study we demonstrate that simultaneous application of ultrasound and SLS leads to modification of the pH profile of the stratum corneum. This pH modification within the stratum corneum's microenvironment, can affect both the structure of the lipid layers and the activity of SLS as a chemical enhancer due to its improved lipophilic solubility. The altered pH profile that results in improved SLS lipophilic solubility, together with improved SLS penetration and dispersion, can explain the synergistic enhancing effect of ultrasound and SLS on transdermal transport.

Algorithms↗
PubMed2004

Ultrasound and transdermal drug delivery.

Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Application of ultrasound to the skin increases its permeability (sonophoresis) and enables the delivery of various substances into and through the skin. This review presents the main findings in the field of sonophoresis, namely transdermal drug delivery and transdermal monitoring. Particular attention is paid to proposed enhancement mechanisms and future trends in the field of cutaneous vaccination and gene delivery.

Administration, Cutaneous↗
PubMed2004

Low-frequency sonophoresis: a review.

Application of ultrasound enhances skin permeability to a variety of molecules (sonophoresis). The enhancement induced by ultrasound is particularly significant at low-frequencies (f<100 kHz, low-frequency sonophoresis). This review summarizes mechanisms and applications of low-frequency sonophoresis. In vitro, in vivo, as well as clinical studies demonstrating the effect of low-frequency ultrasound on transdermal drug delivery and glucose extraction are summarized. Mechanistic insights gained through a number of investigations are also reviewed. Finally, reports on the synergistic effect of low-frequency ultrasound with other enhancers including chemicals and iontophoresis are summarized.

Administration, Cutaneous↗
PubMed2004

Bioadhesive grafted starch copolymers as platforms for peroral drug delivery: a study of theophylline release.

Nonirritant bioadhesive drug release systems based on starch-acrylic acid graft copolymers prepared by radiation of starch and acrylic acid mixtures with (60)Co were developed for buccal application. The release rate of theophylline (TPL), used as a model drug, depended on the ratio of starch to acrylic acid and on the presence of cations in the graft copolymers, but was practically not affected by the pH (between pH 3 and 7) of the dissolution medium nor by the type of starch used (corn, rice, or potato). Possible release mechanisms are discussed for specific conditions. In general, the release behavior of the graft copolymers was found to be non-Fickian, n value being between 0.6 and 0.96, suggesting that the release was controlled by a combination of tablet erosion and the diffusion of the drug from the swollen matrix. Incorporation of divalent cations into the graft copolymers led to a significant decrease in swelling erosion of the tablets as well as a substantial retardation of drug release. Highest work of adhesion was obtained with graft copolymers containing calcium ions as well as longer time of adhesion on dogs' gingiva.

Acrylates↗
PubMed2004

Rapid onset of cutaneous anesthesia with EMLA cream after pretreatment with a new ultrasound-emitting device.

UNLABELLED: In this randomized, double-blinded, placebo-controlled, crossover trial of 42 human subjects, we examined the speed of onset of cutaneous anesthesia by eutectic mixture of local anesthetics (EMLA) cream after brief (approximately 10-s) pretreatment of the underlying skin with low-frequency (55 kHz) ultrasound. Four treatments were compared: ultrasound pretreatment followed by application of 1 g EMLA or placebo cream for 5 min, 10 min, 15 min, and 60 min without ultrasound pretreatment as positive control. Pain was tested by pricks with a 20 g needle. Pain scores and patient preference for EMLA or placebo cream were measured at each time point. Based on both pain scores and patient preference, cutaneous anesthesia was achieved in the EMLA groups as compared with placebo at all time points. After ultrasound pretreatment and then 5, 10, or 15 min after EMLA cream application, pain scores and overall preference were statistically indistinguishable from EMLA cream application for 60 min (without ultrasound pretreatment). There were no significant adverse effects. Low-frequency ultrasound pretreatment appears to be safe and effective in producing rapid onset of EMLA cream in this model, with results as early as 5 min. IMPLICATIONS: A prospective, randomized, double-blinded, placebo-controlled clinical trial demonstrated rapid onset of cutaneous anesthesia by pretreatment of the skin with ultrasound before application of EMLA cream.

Adolescent↗
PubMed2003

Modeling ionic hydrogels swelling: characterization of the non-steady state.

Ionic hydrogels can be used as controlled release systems that respond to an external substrate or trigger by swelling or de-swelling. One example is a glucose-sensitive system for insulin-controlled release based on pH-sensitive hydrogel. To enhance understanding of non-steady state swelling, and to facilitate design of specifications (e.g., glucose-sensitivity) of the pH-sensitive ionic hydrogel based on the copolymer poly (2-hydroxyethyl methacrylate-co-N, N-dimethylaminoethyl methacrylate) (poly (HEMA-co-DMAEMA)), we developed a mathematical compartmental model using the software SAAM II. Current analytical and computational methods focus on equilibrium swelling of hydrogels; although for many stimuli-responsive hydrogel applications, the dynamic process is significant. We now report, using a combination of experimental data and kinetic analysis that in the poly (HEMA-co-DMAEMA) the rate of proton entry is governed by a different rate coefficient than water entry rate. The transport coefficient governing water uptake is dependent upon three variables: pH of external media, amine groups incorporated into the polymer, and crosslinking density of the polymer. An additional result is that swelling equilibrium is reached when all the amine groups are protonated. In this study we also demonstrate the predictive capability of the model for both interpolated and extrapolated data, and its use in design of future bench experiments. Uncovering these fundamental properties of pH-sensitive hydrogels with the aid of a kinetic model suggests that the complexities of hydrogel research and development can be overcome by combining experimental and computational approaches.

Computer Simulation↗
PubMed2003

Pectin-based systems for colon-specific drug delivery via oral route.

Pectin-derived matrices are now being examined and tested for controlled drug delivery. Pectin is intact in the upper gastrointestinal tract and degraded by colonic microflora. The composition of this microflora remains relatively consistent across a diverse human population. Thus, pectin-derived drug carriers provide promising potential for colon-specific drug delivery. This paper reviews recent developments in pectin-derived formulations. Subjects reviewed include gelation of pectin, calcium cross-linked pectinate, composites of pectin and other polymers, technologies to fabricate pectin into useful drug delivery vehicles, and methods to evaluate release kinetics of incorporated drugs. This article discusses advantages, limitations, and possible future developments in pectin-based formulations with particular emphasis on the field of colon-specific drug delivery.

Administration, Oral↗
PubMed2002

Ultrasound-assisted insulin delivery and noninvasive glucose sensing.

Peptides and proteins are emerging as an increasingly important class of drugs as they become more readily available through improvement in recombinant DNA technology and chemical synthesis techniques. The application of peptides and proteins as clinically useful drugs is, however, seriously hampered owing to the substantial delivery problems requiring frequent injections. Considerable effort has been directed therefore to developing painless and convenient methods for delivery of peptides and proteins. In diabetes, in addition to the need of insulin injections there is a need to develop painless and convenient methods to measure blood glucose. This review describes approaches based on the application of ultrasound for noninvasive and painless transdermal glucose sensing and delivery of insulin.

Administration, Cutaneous↗