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Biomedical subjects

A Naik

Publications and source records attributed to A Naik.

At least 19 recordsLinked to original sources
PubMed2006

Cooling a nanomechanical resonator with quantum back-action.

Quantum mechanics demands that the act of measurement must affect the measured object. When a linear amplifier is used to continuously monitor the position of an object, the Heisenberg uncertainty relationship requires that the object be driven by force impulses, called back-action. Here we measure the back-action of a superconducting single-electron transistor (SSET) on a radio-frequency nanomechanical resonator. The conductance of the SSET, which is capacitively coupled to the resonator, provides a sensitive probe of the latter's position; back-action effects manifest themselves as an effective thermal bath, the properties of which depend sensitively on SSET bias conditions. Surprisingly, when the SSET is biased near a transport resonance, we observe cooling of the nanomechanical mode from 550 mK to 300 mK--an effect that is analogous to laser cooling in atomic physics. Our measurements have implications for nanomechanical readout of quantum information devices and the limits of ultrasensitive force microscopy (such as single-nuclear-spin magnetic resonance force microscopy). Furthermore, we anticipate the use of these back-action effects to prepare ultracold and quantum states of mechanical structures, which would not be accessible with existing technology.

Journal Article↗
PubMed2005

Skin permeation enhancement by sucrose esters: a pH-dependent phenomenon.

The purpose of the present study was to evaluate the effect of sucrose esters (particularly, sucrose laureate and sucrose oleate in Transcutol) on the percutaneous penetration of a charged molecule as a function of ionization. We have investigated the influence of these sucrose esters on the in vitro diffusion profiles of lidocaine hydrochloride, a weak ionizable base (pKa=7.9), at different pH values, using porcine ear skin as the barrier membrane. As expected, lidocaine flux in the absence of an enhancer, increased from pH 5 to 9 with a corrresponding increase in the level of the unionized base. However, when skin was pretreated with 2% laureate in Transcutol (2% L-TC), drug permeation was higher at pH 5.0 and 7.0 than at 9.0. A different trend was observed in experiments with 2% oleate in Transcutol (2% O-TC), where skin flux was maximal at a more basic pH, when the degree of ionization is low. The results suggest that sucrose laureate enhances the penetration of the ionized form of the drug (12-fold greater flux relative to control), whereas sucrose oleate is more effective in promoting permeation of the unionized species. The structural properties of the sucrose esters as well as the degree of ionization of the drug are important characteristics affecting the transdermal flux of lidocaine.

Algorithms↗
PubMed2004

Skin penetration and distribution of polymeric nanoparticles.

Encapsulation using nanoparticulate systems is an increasingly implemented strategy in drug targeting and delivery. Such systems have also been proposed for topical administration to enhance percutaneous transport into and across the skin barrier. However, the mechanism by which such particulate formulations facilitate skin transport remains ambiguous. In this study, confocal laser scanning microscopy (CLSM) was used to visualize the distribution of non-biodegradable, fluorescent, polystyrene nanoparticles (diameters 20 and 200 nm) across porcine skin. The surface images revealed that (i) polystyrene nanoparticles accumulated preferentially in the follicular openings, (ii) this distribution increased in a time-dependent manner, and (iii) the follicular localization was favoured by the smaller particle size. Apart from follicular uptake, localization of nanoparticles in skin "furrows" was apparent from the surface images. However, cross-sectional images revealed that these non-follicular structures did not offer an alternative penetration pathway for the polymer vectors, whose transport was clearly impeded by the stratum corneum.

Administration, Cutaneous↗
PubMed2004

Visualization of skin penetration using confocal laser scanning microscopy.

The use of skin as an alternative route for administering systemically active drugs has attracted considerable interest in recent years. However, the skin provides an excellent barrier, which limits the number of drug molecules suitable for transdermal delivery. Thus, in order to improve cutaneous delivery, it is necessary to adopt an enhancement method, either (i) passively using novel formulations, e.g. microemulsions, liposomes, and colloidal polymeric suspensions, or more conventional skin permeation enhancers, or (ii) with a physical approach, such as, iontophoresis, sonophoresis or electroporation. Although there has been much progress, the precise modes of action of the different techniques used are far from well-understood. The objective of this review, therefore, is to evaluate how confocal laser scanning microscopy may contribute to the determination of the mechanisms of diverse skin penetration enhancement strategies.

Administration, Cutaneous↗
PubMed2004

Oral ketamine or midazolam or low dose combination for premedication in children.

This randomized controlled trial was designed to evaluate whether the combination of low dose oral midazolam (0.25 mg/kg) and low dose oral ketamine (3 mg/kg) provides better premedication than oral midazolam (0.5 mg/kg) or oral ketamine (6 mg/kg). Seventy-eight children of ASA physical status I or II scheduled for elective ophthalmic surgery were randomly divided into three groups and given premedication in the holding area 30 minutes before surgery. Two subjects from each group vomited the medication and were excluded, leaving 72 subjects for further analysis. The onset of sedation was earlier in the combination group than the other two groups. At 10 minutes after premedication 12.5% in the combination group had an acceptable sedation score compared with none in the other two groups. After 20 minutes 54% in the combination group had an acceptable sedation score, 21% in the midazolam group and 16% in the ketamine group (P<0.05). There were no significant differences in the parental separation score, response to induction and emergence score. The mean time for best parental separation score was significantly less in the combination group (19+/-8 min) than either the midazolam (28+/-7) or ketamine (29+/-7 min) groups (P<0.05). Recovery was earlier in the combination group, as the time required to reach a modified Aldrete score of 10 was significantly less in the combination group (22+/-5 min) than in the oral midazolam (36+/-11 min) or ketamine (38+/-8 min) groups. The incidence of excessive salivation was significantly higher in the ketamine alone group (P<0.05). In conclusion, the combination of oral ketamine (3 mg/kg) and midazolam (0.25 mg/kg) has minimal side effects and gives a faster onset and more rapid recovery than ketamine 6 mg/kg or midazolam 0.5 mg/kg for premedication in children.

Adjuvants, Anesthesia↗
PubMed2003

Skin permeability enhancement by low frequency sonophoresis: lipid extraction and transport pathways.

The objective of this study was to shed light on the mechanism(s) by which low-frequency ultrasound (20 KHz) enhances the permeability of the skin. The physical effects on the barrier and the transport pathway, in particular, were examined. The amount of lipid removed from the intercellular domains of the stratum corneum following sonophoresis was determined by infrared spectroscopy. Transport of the fluorescent probes nile red and calcein, under the influence of ultrasound, was evaluated by laser-scanning confocal microscopy. The results were compared with the appropriate passive control data and with data obtained from experiments in which the skin was exposed simply to the thermal effects induced by ultrasound treatment. A significant fraction ( approximately 30%) of the intercellular lipids of the stratum corneum, which are principally responsible for skin barrier function, were removed during the application of low-frequency sonophoresis. Although the confocal images from the nile red experiments were not particularly informative, ultrasound clearly and significantly (again, relative to the corresponding controls) facilitated transport of the hydrophilic calcein via discrete permeabilized regions, whereas other areas of the barrier were apparently unaffected. Lipid removal from the stratum corneum is implicated as a factor contributing the observed permeation enhancement effects of low-frequency ultrasound. However, microscopic observations imply that sonophoresis induces localized (aqueous?) permeation pathways at discrete sites.

Administration, Cutaneous↗
PubMed2002

Reverse iontophoretic monitoring in premature neonates: feasibility and potential.

Premature neonates represent a fragile patient population, often subjected to intensive clinical care and multiple drug therapy, which must be monitored carefully and continuously. The difficult and painful nature of repetitive blood sampling, particularly in this population, has provided considerable impetus for the development of noninvasive methods for monitoring blood analytes. Reverse iontophoresis, a relatively new technology already used for the transdermal monitoring of blood glucose levels in adults, may be particularly well-suited to exploit the unique properties of preterm neonatal skin. The underdevelopment of the premature infant's epidermis, and more specifically the stratum corneum (SC), results in an increased permeability to molecular transport. In this study, we have investigated the feasibility of reverse iontophoretic monitoring of two model drugs, caffeine and theophylline, which are often administered to premature neonates. To this purpose, tape-stripped porcine skin in vitro, which has been previously demonstrated to be an excellent model for premature neonatal skin, was employed. Reverse iontophoresis across intact membranes enabled a quantifiable extraction of both drugs predominantly at the cathode compartment. The mechanism of extraction of these essentially neutral drugs (caffeine and theophylline being uncharged at pH 7.4) was electroosmosis. However, when the SC was removed by progressive tape-stripping, the amounts of drugs extracted by reverse iontophoresis were equivalent to those obtained by passive diffusion. In these circumstances, therefore, the benefit and usefulness of the applied electric field had been lost. In summary, the absence of an at least partially functional skin barrier obviates, in the case of neutral molecules, the control (and directional transport) offered by iontophoresis; in contrast, for ionized species, where the principal iontophoretic transport mechanism is electromigration, the approach should be valid.

Animals↗
PubMed2001

Piroxicam delivery into human stratum corneum in vivo: iontophoresis versus passive diffusion.

A nonsteroidal anti-inflammatory drug, piroxicam, was administered from a commercially available gel to human volunteers both passively and under the application of an iontophoretic current. The effect of occlusion on the passive delivery of piroxicam was also examined in a separate series of experiments. After treatment, the stratum corneum (SC) at the site of application was progressively tape-stripped and piroxicam transport into the membrane was assessed by UV-analysis of drug extracted from the tape-strips. Analysis of variance did not show any significant difference between passive piroxicam delivery after 30, 60 or 125 min. However, current application enhanced drug uptake into the SC, as indicated by both increased piroxicam concentrations in the horny layer and detectable concentrations at greater depths into the membrane. The total amount of drug recovered in the SC post-iontophoresis was significantly higher than that found following passive diffusion for each application time. The amounts of drug recovered from the tapes after 60 and 125 min of current application were significantly higher than that after 30 min treatment. Finally, the in vivo SC concentration profiles following passive delivery were fitted to the appropriate solution of Fick's second law of diffusion to determine skin partitioning and diffusivity parameters.

Administration, Cutaneous↗
PubMed2001

Effect of ethanol and isopropyl myristate on the availability of topical terbinafine in human stratum corneum, in vivo.

PURPOSE: The objective of this study was to determine the availability of the topical drug terbinafine (TBF) in human stratum corneum (SC) in vivo following its administration in formulations containing isopropyl myristate and ethanol. METHODS: The ventral forearms of human volunteers were treated for 4 h with TBF, at a concentration equal to 1/4 saturation, in isopropyl myristate (IPM), in ethanol (EtOH) and in 50:50 v/v IPM/EtOH. At the end of the application period, the treated sites were carefully cleaned of excess vehicle and the SC was progressively removed by sequential tape stripping. TBF was quantified in the SC by: (a) extraction of the tape strips and subsequent HPLC analysis; and (b) attenuated total reflectance infrared spectroscopy (ATR-FTIR) of each sequentially exposed SC surface during the tape stripping procedure. RESULTS: The concentration profile of TBF in the SC (i.e. drug concentration as a function of depth in the membrane) was fitted to the appropriate solution of Fick's second law of diffusion, allowing thereby the drug's SC/vehicle partition coefficient (K) and characteristic diffusion parameter (D/L(2), where D is the diffusivity of TBF in the SC of thickness L) to be deduced. CONCLUSIONS: While D/L(2) for TBF derived from the three vehicles remained essentially constant, the drug's partitioning into the SC was significantly higher from formulations containing ethanol. Both the semi-quantitative infrared data and the more rigorous HPLC results supported these deductions.

Adult↗
PubMed2001

In vivo assessment of enhanced topical delivery of terbinafine to human stratum corneum.

PURPOSE: The objective of this study was to evaluate, using attenuated total reflectance Fourier transform infrared spectroscopy, the stratum corneum (SC) bioavailability of terbinafine (TBF) following topical treatment with four different formulations. METHODS: Four skin sites on the ventral forearms of five healthy volunteers were treated for 2 h using one of four formulations based on a vehicle consisting of 50% ethanol and 50% isopropyl myristate. Three of these formulations included a percutaneous penetration enhancer: either 5% oleic acid, 10% 2-pyrrolidone or 1% urea. The SC concentration profile of TBF was measured by repeated infrared spectroscopic measurements while sequentially stripping off the layers of this barrier membrane with adhesive tape. This method was validated by HPLC analysis of TBF extracted from the stripped tapes. Transepidermal water loss (TEWL) measurements were also performed, to permit facile estimation of SC thickness. RESULTS: The SC concentration profiles of TBF were fitted to the appropriate solution of Fick's second law of diffusion, thereby allowing determination of the characteristic diffusion and partitioning parameters of the permeating drug. This analysis enabled the efficacies of the different formulations tested to be compared to the no-enhancer control. While it was found that the formulation containing 5% oleic acid significantly enhanced the SC availability of TBF, the other formulations did not improve the apparent drug delivery. CONCLUSIONS: A facile and minimally invasive methodology to evaluate an important aspect of topical drug bioavailability has been described. The analytical methods used (infrared spectroscopy and HPLC) allow estimates of both relative and absolute drug bioavailability in the SC and may be useful, therefore, in the critical determination of bioequivalence between topical formulations.

Administration, Topical↗
PubMed2001

Computer-aided design (CAD) of Mn(II) complexes: superoxide dismutase mimetics with catalytic activity exceeding the native enzyme.

New Mn(II) macrocyclic pentaamine complexes derived from the biscyclohexyl-pyridine complex, M40403 ([manganese(II)dichloro[(4R,9R,14R,19R)-3,10,13,20,26-pentaazatetracyclo[20.3.1.0.(4,9)0(14,19)]hexacosa-1(26),-22(23),24-triene]]), are described here. The complex M40403 was previously shown to be a superoxide dismutase (SOD) catalyst with rates for the catalytic dismutation of superoxide to oxygen and hydrogen peroxide at pH = 7.4 of 1.2 x 10(+7) M(-1) s(-1).(1) The use of the computer-aided design paradigm reported previously for this class of Mn(II) complexes(2,3) led to the prediction that the 2S,21S-dimethyl derivative of M40403 should possess superior catalytic SOD activity. The synthesis of this new macrocyclic Mn(II) complex, [manganese(II)dichloro[2S, 21S-dimethyl-(4R,9R,14R,19R)-3,10,13,20,26-pentaazatetracyclo[20.3.1.0.(4,9)0(14,19)]hexacosa-1(26),22(23),24-triene]], 5, was accomplished via a high yield template condensation utilizing the linear tetraamine, N,N'-Bis[(1R,2R)-[2-(amino)]cyclohexyl]-1,2-diaminoethane, 1, 2,6-diacetylpyridine, and MnCl(2) to form the macrocyclic diimine complex, 2, which then is reduced. The two other possible dimethyl diastereomers of 5 (2R,21R-dimethyl,3, and 2R,21S-dimethyl, 6) were also prepared via reduction of the diimine complex 2. Two of these complexes, 3 and 5, were characterized by X-ray structure determination confirming their absolute stereochemistry as 2R,21R-dimethyl and 2S,21S-dimethyl, respectively. The results of the MM calculations which predict that the 2S,21S-dimethyl complex, 5, should be a high activity catalyst and that the 2R,21R-dimethyl complex, 3, should have little or no catalytic activity are presented. The catalytic SOD rates for these complexes are reported for each of these complexes and a correlation with the modeling predictions is established showing that 2R,21R-complex, 3, has no measurable catalytic rate, while the 2R,21S complex, 6, is identical to M40403, and the 2S,21S- complex, 5, possesses a very fast rate at pH = 7.4 of 1.6 x 10(+9) M(-1) s(-1) exceeding that of the native mitochondrial MnSOD enzymes.

Catalysis↗
PubMed2001

Permeation enhancement of a highly lipophilic drug using supersaturated systems.

The potential of supersaturation as a method for enhancing the membrane permeation of highly lipophilic compounds has been investigated using, as a model system, the transport of a lavendustin derivative (LAP, log K(o/w) = 5) through silicone membrane. Propylene glycol-water mixtures, which permitted the formulation of LAP at different levels of saturation, were prepared and tested for stability prior to conducting membrane permeation studies. The transport of LAP across silicone membrane from donor solutions containing the drug at different degrees of saturation (DS = 1-5) was evaluated by two independent experimental methods: (i) using attenuated total-reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and (ii) using standard vertical diffusion cells followed by quantification with high-performance liquid chromatography (HPLC). Both methods demonstrated a linear relationship between the DS of the applied solution and the flux through the membrane, yielding similar values for the diffusion coefficients of LAP [diffusion cells, D = 1.75 ( +/- 0.16) x 10(-7) cm(2) s(-1) and ATR-FTIR, D = 1.42 ( +/- 0.26) x 10(-7) cm(2) s(-1)). In addition to the characterization of LAP permeation, ATR-FTIR spectroscopy enabled an examination of solvent transport across the membrane.

Diffusion Chambers, Culture↗
PubMed2001

Passive skin penetration enhancement and its quantification in vitro.

The poor penetration of drugs into the skin (and, partially, the permeation across the stratum corneum) often limits the efficacy of topical formulations. Basically, skin penetration can be enhanced by the following strategies: (i) increasing drug diffusivity in the skin; (ii) increasing drug solubility in the skin, and/or (iii) increasing the degree of saturation of the drug in the formulation. In this article, we review the literature with respect to: (i) chemical penetration enhancers, which have been shown to influence the diffusivity and/or solubility of the drug in the skin and (ii) supersaturated formulations, in which the degree of saturation of the drug is increased compared to conventional formulations. In addition, three different in vitro methods, specifically, classic diffusion cell studies, attenuated total-reflectance-Fourier transform infrared spectroscopy, and tape stripping in conjunction with an appropriate analytical technique, are considered, emphasizing their application to obtain quantitative values for skin transport parameters and to separate the kinetic or thermodynamic effects of an enhancement strategy.

Administration, Cutaneous↗
PubMed2001

Assessment of topical bioavailability in vivo: the importance of stratum corneum thickness.

We present a method to determine the cutaneous bioavailability and hence to evaluate the bioequivalence of topically applied drugs in vivo. The procedure uses serial tape-stripping and transepidermal water loss measurements to quantify the thickness of the removed stratum corneum (SC) and to determine the intact membrane thickness. Following tape-stripping, the drug is extracted from the tapes and assayed, e.g., by HPLC. This provides a drug concentration profile as a function of the normalized position within the SC. The data are fitted to a solution of Fick's second law of diffusion in order to calculate characteristic membrane transport parameters. Integration of the concentration profile over the entire SC thickness, that is, the 'area-under-the-curve', provides a measure of the cutaneous bioavailability and hence can be used to assess the bioequivalence of topically applied drugs.

Administration, Topical↗
PubMed2001

Short stays in hospice. A review & update.

Despite the proven benefits and popularity of hospice, the average hospice patient receives only one month of services before death. Advanced progression of a patient's disease at admission contributes to short lengths of stay, and precludes patients from receiving the full benefit of hospice services. This article uses the results of the literature review to articulate reasons for delayed enrollment and to advance suggestions for ameliorating the problem of short stay in hospice.

Disease Progression↗