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Biomedical subjects

J Kost

Publications and source records attributed to J Kost.

At least 19 recordsLinked to original sources
PubMed2002

Dependence of low-frequency sonophoresis on ultrasound parameters; distance of the horn and intensity.

Sonophoresis at a frequency of 20 kHz has been shown to enhance transdermal drug delivery, a phenomenon referred to as low-frequency sonophoresis. This study provides an investigation of the dependence of low-frequency sonophoresis on various ultrasound parameters, including the distance of the horn from the skin, intensity, and frequency. We performed in vitro experiments with full thickness pig skin to measure enhancements of skin conductivity and drug permeability. Ultrasound was applied to pretreat the skin using a sonicator operating at a frequency of either 20 or 40 kHz. We also measured pitting of aluminum foil to measure cavitation, which is the principal mechanism of low-frequency sonophoresis. The skin conductivity enhancement was found to be inversely proportional to the distance of the horn from the skin. As the intensity increased, skin conductivity enhancement also increased up to a certain threshold, and then dropped off. The intensities (I(max)) at which maximum enhancement occur are about 14 W/cm2 for 20 kHz and 17 W/cm2 for 40 kHz. These findings may be useful in optimizing low-frequency sonophoresis. Overall, the dependence of transport on ultrasound parameters is similar to that of aluminum foil pitting. These results support the role of cavitation in low-frequency sonophoresis.

Administration, Cutaneous↗
PubMed2001

Responsive polymeric delivery systems.

This paper discusses the state of the art in a relatively new approach in the field of controlled drug delivery-responsive polymeric drug delivery systems. Such systems are capable of adjusting drug release rates in response to a physiological need. The fundamental principles of externally and self-regulated delivery systems are examined. Special attention is paid to specific clinical settings such as diabetes, presenting the advantages and disadvantages of different approaches.

Animals↗
PubMed2001

Assessment of murine bladder permeability with fluorescein: validation with cyclophosphamide and protamine.

OBJECTIVES: Bladder hyperpermeability should result in elevated blood levels of intravesically administered agents. Reabsorption from a hyperpermeable bladder should result in prolonged urinary excretion of an agent after parenteral administration. To test these hypotheses, urinary clearance and plasma levels of sodium fluorescein (NaF) were measured in mice before and during cyclophosphamide (CYP) and protamine-induced hemorrhagic cystitis. METHODS: To measure the plasma uptake of NaF from the bladder, 10 mg/mL NaF was instilled, either by catheter or retrograde urethral infusion, 15 minutes before retro-orbital or ventricular sampling. The plasma levels were measured 24 hours and 14 days after exposure to CYP 300 mg/kg or 15 minutes after instillation of protamine 10 mg/mL. Hourly urine concentrations were measured immediately after intraperitoneal administration of 10 mg/kg NaF. Pretreatment samples were compared with those obtained 24 hours after intraperitoneal administration of 300 mg/kg CYP. RESULTS: Urinary NaF excretion was delayed in CYP-exposed mice. A bi-exponential model provided an appropriate fit of the data, both before and after CYP administration. The plasma levels of NaF were significantly elevated at 24 hours and 14 days after CYP exposure when sampled by ventricular nick or retro-orbitally. The median concentration of fluorescein in the protamine-treated mice was significantly higher than in the control mice. CONCLUSIONS: Fluorescein can be used to measure alterations in bladder permeability after bladder mucosal injury in mice. Urinary excretion of NaF is a bi-exponential process that is delayed after bladder mucosal injury, presumably because of increased mucosal permeability and resorption from the urine into the bloodstream.

Analysis of Variance↗
PubMed2001

Transdermal delivery of heparin and low-molecular weight heparin using low-frequency ultrasound.

UNLABELLED: PURPOSE. Heparin and low-molecular weight heparin (LMWH) are the most commonly used anticoagulants and are administered by intravenous or subcutaneous injections. However, injections of heparin have the potential risk of bleeding complications and the requirement of close monitoring in some cases. We hypothesized that transdermal delivery of heparin may provide an attractive alternative to injections. However, the dose of transdermally delivered heparin is limited by low skin permeability. METHODS: We increased skin permeability to heparin and LMWH using low-frequency (20 kHz) ultrasound. Biologic activity of transdermally delivered heparin was measured by using activated clotting time assays and by using anti-Xa (aXa) activity. Structural integrity of heparin was also assessed by using gel electrophoresis. RESULTS: Low-frequency ultrasound increased permeability of pigskin in vitro and rat skin in vivo and allowed delivery of biologically active doses of heparin and low-molecular weight heparin transdermally. A prolonged contact of transdermally delivered heparin with pigskin was found to reduce the biologic activity of heparin, although no such deactivation was observed during short exposures. Transdermally delivered LMWH resulted in sustained aXa levels in the blood. This result was in strong contrast to subcutaneous or intravenous injections of LMWH, which resulted in only temporary elevations of aXa level. CONCLUSIONS: Transdermal delivery of low-molecular weight heparin is a potential alternative to injections.

Administration, Cutaneous↗
PubMed2000

Characterization of a polymeric PLGA-injectable implant delivery system for the controlled release of proteins.

Physico-chemical properties of injectable polymeric implant systems, based on the principle that a water-insoluble polymer dissolved in a biocompatible solvent will precipitate upon contact with water, were studied and utilized to predict the release of proteins from these systems. Polylactide-co-glycolide copolymer (PLGA) and glycofurol were chosen since they both have pharmaceutical precedence. Changes in polymer composition, its weight percent in solution, molecular weight, and protein loading level were assessed to provide formulations with the desired release rates and duration of release.

Animals↗
PubMed2000

Determination of threshold energy dose for ultrasound-induced transdermal drug transport.

Low-frequency (20 kHz) ultrasound has been shown to enhance transdermal transport of drugs, a phenomenon referred to as sonophoresis. In this paper, we report the threshold energy dose for ultrasound-induced transdermal drug transport. The threshold was determined by in vitro measurements of the dependence of sonophoretic enhancement on ultrasound parameters, including intensity, duty cycle, and exposure time. While the enhancement varies linearly with ultrasound intensity and exposure times, it is independent of the duty cycle in the range of parameters studied. The enhancement is also directly proportional to the ultrasound energy density once the threshold value is crossed. For full thickness pig skin, the threshold value is about 222 J/cm(2). The overall dependence of transport enhancement on ultrasound parameters is similar to that of cavitation measured in a model system, pitting of aluminum foil. Specifically, the extent of pitting is proportional to ultrasound intensity and exposure time and is independent of duty cycle. Furthermore, the extent of pitting is also proportional to the ultrasound energy density. The similarity between the parametric dependence of transport enhancement and cavitation is consistent with previous findings that cavitation plays the dominant role in sonophoresis.

Administration, Cutaneous↗
PubMed2000

Synergistic effect of low-frequency ultrasound and sodium lauryl sulfate on transdermal transport.

Application of low-frequency ultrasound has been shown to enhance transdermal transport of drugs (low-frequency sonophoresis). In this paper, we show that the efficacy of low-frequency ultrasound in enhancing transdermal transport can be further increased by its combination with sodium lauryl sulfate (SLS), a well-known surfactant. The dependence of the ultrasound-SLS-mediated transport on ultrasound parameters, including intensity, net exposure time, and duty cycle, is discussed. The transdermal transport enhancement is proportional to ultrasound intensity as well as to exposure time, and is independent of duty cycle as long as the net exposure time is the same. The synergistic effect of SLS and ultrasound on transdermal transport increases linearly with SLS concentration. The enhancement is also proportional to the ultrasound energy density beyond a threshold value, which suggests that a certain minimum amount of energy density is required before noticeable changes in skin permeability occur. A similar dependence of the transdermal transport enhancement on energy density is observed in the case of the enhancement induced by ultrasound alone. Although the threshold energy density value in the presence of SLS is about 10 times lower than that in the case of ultrasound alone, the relationship between enhancement and energy density in the presence and in the absence of SLS is otherwise similar. Possible mechanisms for the synergistic effect of ultrasound and SLS are also discussed.

Aluminum↗
PubMed2000

Characterization of glucose-sensitive insulin release systems in simulated in vivo conditions.

We studied the glucose-responsive insulin controlled release system based on the hydrogel poly(2-hydroxyethyl methacrylate-co-N,N-dimethylaminoethyl methacrylate), also called poly(HEMA-co-DMAEMA), with entrapped glucose oxidase, catalase and insulin. When exposed to physiological fluids, glucose diffuses into the hydrogel, glucose oxidase catalyzes the glucose conversion to gluconic acid, causing swelling of the pH-sensitive hydrogel and subsequently increased insulin release. The higher the glucose concentration in the medium, the higher and faster the swelling and release rates. The effects of polymer morphology and oxygen availability on hydrogel swelling and on insulin release kinetics were tested. Polymer morphology was modified by changing the crosslinking agent (tetraethylene glycol dimethacrylate) concentration (0-0.95 vol%). Oxygen availability was modified by changing the immobilized catalase concentration (0-15 units catalase per unit glucose oxidase) and by bubbling oxygen through the medium. The results indicated that: (i) Hydrogels without crosslinking agent were found to be stable in water, and their sensitivity to pH and glucose was higher than the chemically crosslinked hydrogels. (ii) Immobilization of catalase in addition to glucose oxidase in hydrogels prepared without crosslinking agent, resulted in enhanced swelling kinetic. In addition, we carried out primary in vivo experiments on rats, which demonstrated that at least some of the entrapped insulin retains its active form and is effective in reducing blood glucose levels. Moreover, no tissue encapsulation was observed around matrices implanted in the peritoneum. In conclusion, the pH-sensitive hydrogel poly(HEMA-co-DMAEMA) can be manipulated to produce glucose-responsive insulin release system that is effective in reducing blood glucose levels.

Animals↗
PubMed2000

Transdermal extraction of analytes using low-frequency ultrasound.

PURPOSE: Transdermal extraction of clinically relevant analytes offers a potentially non-invasive method of diagnostics. However, development of such a method is limited by the low skin permeability. In this paper, we report a potential method for non-invasive diagnostics based on ultrasonic skin permeabilization and subsequent extraction of interstitial fluid (ISF) across the skin. METHODS: In vivo experiments were performed using Sprague Dawley rats to assess ultrasound-induced skin permeabilization and subsequent extraction of various analytes. Serum and ISF concentrations of various analytes were measured. RESULTS: Application of low-frequency ultrasound rapidly increased skin permeability. Skin remained in a state of high permeability for at least three hours. During this period, application of vacuum extracted ISF across rat skin in vivo at a rate of 25.7 microl/cm2/hr. We measured concentrations of various analytes including glucose, albumin, calcium, urea, triglycerides, lactate, and dextran in transdermally extracted fluid. The composition of the fluid extracted transdermally is similar to that of ISF. CONCLUSIONS: Application of low-frequency ultrasound allows skin permeabilization and extraction of ISF across the skin.

Animals↗
PubMed2000

Analysis of ultrasonically extracted interstitial fluid as a predictor of blood glucose levels.

Transdermal extraction of clinically relevant analytes offers a potentially noninvasive method of diagnostics. However, development of such a method is limited by the low permeability of skin. In this paper, we present a potential method for noninvasive diagnostics based on ultrasonic skin permeabilization and subsequent extraction of interstitial fluid (ISF) across the skin using vacuum. ISF extracted by this method was collected and analyzed for glucose and other analytes. Glucose concentration in the extracted fluid correlates well with blood glucose concentration over a range of 50-250 mg/dl. A mathematical model describing vacuum-induced transport of ISF through ultrasonically permeabilized skin is presented as well. The model accounts for convective, as well as diffusive, transport processes across blood capillaries, epidermis, and the stratum corneum. The overall predictions of the model compare favorably with the experimental observations.

Animals↗
PubMed1998

Electrical properties of glucose-sensitive hydrogels: swelling and conductivity relationships.

The electrical characteristics of a glucose-sensitive polymeric hydrogel have been studied. The hydrogel matrices were prepared by radical polymerization of solutions containing 2-hydroxyethyl methacrylate, N,N-dimethyl aminoethyl methacrylate, tetraethylene glycol dimethacrylate, ethylene glycol, water, and glucose oxidase. The hydrogels displayed faster and higher swelling rates for lower levels of a crosslinking agent. Electrical conductivity was found to be a sensitive measurement of the state of the swelling. A simple model that relates hydrogel swelling and conductivity has been proposed.

Electric Conductivity↗
PubMed1998

Mass transport enhancement by ultrasound in non-degradable polymeric controlled release systems.

In this work, an attempt was made to characterize mass transport enhancement in non-erodible polymeric matrices, caused by ultrasound. It was found that drug release rates from polymeric matrices exposed to ultrasound, can be controlled by modifying parameters like: ultrasound frequency, molecular weight of the incorporated drug and structure of the polymeric matrix (size of pores in the network). It is suggested that the enhancing effect of ultrasound on drug release from non-erodible polymers is due to the contribution of a convective term, generated by cavitation, without any destructive effect on morphology of the polymer. This phenomenon was found to be more pronounced in systems which are mass-transport limited.

Drug Carriers↗