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Biomedical subjects

P Santi

Publications and source records attributed to P Santi.

At least 19 recordsLinked to original sources
PubMed2006

New transdermal bioadhesive film containing oxybutynin: In vitro permeation across rabbit ear skin.

Oxybutynin is used extensively in the treatment of patients with overactive bladder. The aim of this work was to realize and test in vitro a new transdermal bioadhesive film containing oxybutynin. Transdermal films were prepared by dissolving in water an adhesive (Plastoid), a film-forming polymer (polyvinyl alcohol), a plasticizer (sorbitol) and the drug. The mixture was then spread on siliconized paper and oven-dried. Permeation experiments were conducted in Franz-type diffusion cells using rabbit ear skin as barrier. The donor compartment contained a water solution, the prepared film (with or without backing) or the commercial patch (Oxytrol). The experiments were performed for 24h. Oxybutynin showed good permeation characteristics across the skin. When the film was applied in occlusive conditions the release profiles were much higher than in non-occlusive conditions, reaching 50% of drug permeated after 24h. Compared to the commercial patch Oxytrol, the film was more efficient suggesting that a smaller area or a lower drug loading could be employed. The results obtained show that the bioadhesive film can be a promising and innovative therapeutic system for the transdermal administration of oxybutynin.

Administration, Cutaneous↗
PubMed2006

Bioadhesive monolayer film for the in vitro transdermal delivery of sumatriptan.

The work presented here aims to develop a bioadhesive monolayer film containing sumatriptan as adjuvant for the treatment of headache pain in a severe migraine attack. Permeation experiments were performed from the films prepared and from the respective solution, to evaluate the relevant permeation parameters. The effect of the penetration enhancers Transcutol, 2-pyrrolidone, and polyethylene glycol 600 was evaluated. The results obtained show that Transcutol and 2-pyrrolidone decreased sumatriptan permeation from solution, whereas a modest increase was produced by polyethylene glycol 600. The enhancers produced the same effects when they were included in the film. Compared to solution, the film showed a higher sumatriptan flux in the early times of the experiment. When the film was applied in occlusive conditions the profiles were much higher, indicating the importance of patch drying. Concerning skin retention, the bioadhesive film produced a reduction of the amount of sumatriptan remaining in the skin, but this can be advantageous in the control of drug input, since it reduces the reservoir effect in the skin and allows for an immediate interruption of drug input when the patch is removed.

Administration, Cutaneous↗
PubMed2005

Half-life of the doubly magic r-process nucleus 78Ni.

Nuclei with magic numbers serve as important benchmarks in nuclear theory. In addition, neutron-rich nuclei play an important role in the astrophysical rapid neutron-capture process (r process). 78Ni is the only doubly magic nucleus that is also an important waiting point in the r process, and serves as a major bottleneck in the synthesis of heavier elements. The half-life of 78Ni has been experimentally deduced for the first time at the Coupled Cyclotron Facility of the National Superconducting Cyclotron Laboratory at Michigan State University, and was found to be 110(+100)(-60) ms. In the same experiment, a first half-life was deduced for 77Ni of 128(+27)(-33) ms, and more precise half-lives were deduced for 75Ni and 76Ni of 344(+20)(-24) ms and 238(+15)(-18) ms, respectively.

Journal Article↗
PubMed2005

Effect of lactic acid and iontophoresis on drug permeation across rabbit ear skin.

The aim of this paper was to explore the efficacy of lactic acid as permeation enhancer for drug molecules across the skin. Three model permeants were chosen: acetaminophen (non-ionized), buspirone hydrochloride (cationic drug) and ibuprofen lysine (anionic drug). We also explored the association of lactic acid and iontophoresis as a means of enhancing drug delivery. Permeation experiments were performed in vitro, using rabbit ear skin as barrier. The results obtained indicate that lactic acid has some effects on model drug permeation across the skin. The effect was more evident with the anionic drug ibuprofen. Cathodal intophoresis increased ibuprofen transport, but when lactic acid was associated with cathodal iontophoresis, a concentration-dependent reduction of ibuprofen iontophoretic flux was observed, probably for the competition by the co-ion. The application of electric current (anodal iontophoresis) to a solution of acetaminophen produced an increase in its transport, due to the presence of an electroosmotic contribution; however, the effect of the association of anodal iontophoresis and lactic acid produced no further enhancement.

Acetaminophen↗
PubMed2004

In vivo experimental testing and model identification of human scalp skin.

A comprehensive experimental/numerical procedure is formulated and validated for the in vivo characterization of the mechanical properties of human skin and the simulation of reconstructive surgery. The procedure uses in vivo experimental tests on undermined skin flaps, which can be performed during surgery, a numerical model formulated within the framework of nonlinear finite strain elasticity and a nonlinear parameter identification technique for the calibration of the model from indirect measurements. The procedure is applied to characterize the scalp skin tested in Raposio and Nordström (Skin Res. Technol. 4 (1998) 94). The skin is treated as a time independent, isotropic and hyperelastic membrane and the problem is solved through a finite element discretization. The study highlights that the model parameters can be determined with good accuracy using displacement measurements of a few points in the domain.

Biomechanical Phenomena↗
PubMed2004

Alpha-tocopherol pro-vitamins: synthesis, hydrolysis and accumulation in rabbit ear skin.

We synthesized esters of alpha-tocopherol (VE) with the aim to develop new pro-vitamins, easily reconverted by enzymes in the skin and able to release another active moiety such as an amino acid, in order to obtain a synergic effect. In particular, the attention was dedicated to the amino acids glycine and alanine and to pyroglutamic acid. The sensitivity of pro-vitamins to enzymatic hydrolysis was evaluated in vitro using porcine liver esterase. Permeation experiments were performed using rabbit ear skin, for the quantification of pro-vitamins and derived VE in the epidermis and dermis. The new derivatives synthesized, and in particular the glycine and alanine derivatives, accumulated in rabbit skin in a significant extent and originated substantial amounts of alpha-tocopherol. In comparison with the acetate derivative (VEAc), the amounts accumulated are comparable or higher. Moreover, the new derivatives, being more hydrophilic, allow the use of vehicles such as the mixture water/propylene glycol/ethanol widely employed for the preparation of creams and gels. Finally, the enzymatic metabolism of these new derivatives generates not only VE, but also components that can have a further advantageous action on skin.

Alanine↗
PubMed2004

New approach for measuring properties of rp-process nuclei.

A new experimental approach was developed that can reduce the uncertainties in astrophysical rapid proton capture (rp) process calculations due to nuclear data. This approach utilizes neutron removal from a radioactive ion beam to populate the nuclear states of interest. Excited states were deduced by the gamma-decay spectra measured in a semiconductor Ge-detector array. In the first case studied, 33Ar, excited states were measured with uncertainties of several keV. The 2 orders of magnitude improvement in the uncertainty of the level energies resulted in a 3 orders of magnitude improvement in the uncertainty of the calculated 32Cl(p,gamma)33Ar rate that is critical to the modeling of the rp process. This approach has the potential to measure key properties of almost all interesting nuclei on the rp-process path.

Journal Article↗
PubMed2003

Buccal delivery of thiocolchicoside: in vitro and in vivo permeation studies.

Thiocolchicoside, a muscle-relaxant agent, is administered by the oral, intra-muscular and topical route. After oral administration the extent of bioavailability compared with intra-muscular administration is low, due to a first pass effect. In this paper, the delivery of thiocolchicoside through oral mucosa is studied to improve the bioavailability. Thiocolchicoside in vitro permeation through porcine oral mucosa and in vivo buccal transport in humans were investigated. Two dosage forms, a bioadhesive disc and a fast dissolving disc for buccal and sublingual administration of thiocolchicoside, respectively, were designed. The in vitro permeation of thiocolchicoside through porcine buccal mucosa from these dosage forms was evaluated and compared with in vivo absorption. Results from in vitro studies demonstrated that thiocolchicoside is quite permeable across porcine buccal mucosa and that permeation enhancers, such as sodium taurocholate and sodium taurodeoxycholate, were not able to increase its flux. The in vivo thiocolchicoside absorption experiments, in which the drug loss from oral cavity was measured, indicated that both formulations could be useful for therapeutic application. The fast dissolving (sublingual) form resulted in a quick uptake of 0.5 mg of thiocolchicoside within 15 min whereas with the adhesive buccal form the same dose can be absorbed over an extended period of time.

Administration, Buccal↗
PubMed2003

Inositol-specific phospholipase C in low and fast proliferating hepatoma cell lines.

Inositol lipid cycle, among the pletora of signalling events, is directly involved in cell growth. It is located both in the cytoplasm and in the nucleus. Disturbances may cause uncontrolled proliferation of the cell and ultimately cancer. The phosphatidyl inositol phospolipase C (PLC) is a key enzyme in the hydrolysis of polyphosphoinositides (PIs) and could be differently involved in the normal and pathological cell growth. We report immunochemical and immunocytochemical demonstrations that the PLC isoforms are present in both cytoplasmic and nuclear compartments of low and fast proliferating hepatoma cells. The PLC activity is increased in fast proliferating cells, in which PLC delta1 and to a greater extent PLC delta4 are more expressed at cytosolic level, suggesting an involvement of PI specific PLCs in the progression of cell cycle and in the control of cell proliferation and possibly of neoplastic cell growth.

Animals↗
PubMed2002

Caffeine microparticles for nasal administration obtained by spray drying.

This study investigated the possibility to use spray drying technique to prepare powders formulations containing caffeine intended for nasal delivery. Spray dried powders containing caffeine and excipients, as filler and shaper agents, were prepared. Powders were investigated for particle size, morphology and delivery properties from Monopowder P nasal insufflator, assessing the influence of each excipient on microparticles characteristics. The results showed that the excipients strongly affected microparticle properties. Size, shape and agglomeration tendency are relevant characteristics of spray dried nasal powder.

Administration, Intranasal↗
PubMed2002

Influence of layer position on in vitro and in vivo release of levodopa methyl ester and carbidopa from three-layer matrix tablets.

A versatile oral controlled release system for the simultaneous delivery of levodopa methyl ester and carbidopa, consisting of a three-layer matrix tablet, has been studied and developed. Each individual layer of the matrix exhibited a different release mechanism, i.e. the first layer was swellable (S), the second one was erodible (E) and the third one was disintegrating (D). The three layers have been assembled in the monolithic matrix in different relative positions. It was found that in the monolith the three layers could interact, producing in vitro release profiles depending on their relative position. The monoliths having the configurations DSE and SDE were administered to human volunteers in order to determine the plasma profiles. The pharmacokinetic data showed a significant difference between the early time plasma curves: the monolith DSE, having the fast release profile, gave rise to a rapid appearance of a high levodopa plasma level, whereas the slower releasing monolith SDE produced a smoothed plasma concentration profile.

Administration, Oral↗
PubMed2001

Direct measurement of the L/K ratio in (7)Be electron capture.

The ratio of L- to K-shell electron captures in light nuclei is particularly sensitive to electron overlap and exchange effects. Calculations of these effects in (7)Be disagree by more than 20%. We report a measurement of the L/K ratio in (7)Be, using a cryogenic microcalorimeter which clearly separates L- and K-shell captures. The obtained L/K ratio of 0.040(6) is less than half that of existing predictions for free (7)Be. The discrepancy is likely due to in-medium effects distorting the L-shell electron orbitals.

Journal Article↗
PubMed2001

Translocation of drug particles in HPMC matrix gel layer: effect of drug solubility and influence on release rate.

The aim of this work was to study the release mechanisms of drugs having different solubility (buflomedil pyridoxalphosphate 65%, sodium diclofenac 3.1%, nitrofutantoin 0.02% w/v,) from hydroxypropyl methylcellulose (HPMC) matrices by concomitantly studying swelling, diffusion and erosion fronts movement and drug delivery. The main goal was to clarify the role played by polymer swelling in drug transport. The results showed that the rate and amount of drug released from swellable matrices was dependent not only from drug dissolution and diffusion but also from solid drug translocation in the gel due to polymer swelling. In fact, as drug solubility decreased, the slower drug dissolution rate in the gel layer allowed drug particles to be transported close to the matrix erosion front. The presence of solid particles in the gel reduced the swelling and the entanglement of polymer chains and affected the resistance of gel towards erosion. As a consequence, the matrix became more erodible. The erosive delivery accelerated after the matrix had been completely transformed into the rubbery state, particularly when a considerable amount of solid drug particles remained in the gel phase.

Diclofenac↗
PubMed2001

Design of triptorelin loaded nanospheres for transdermal iontophoretic administration.

Triptorelin is a decapeptide analog of luteinizing hormone releasing hormone, currently used for the treatment of sex-hormones dependents diseases. The aim of this work was to prepare triptorelin-loaded nanospheres useful for transdermal iontophoretic administration. Nanospheres were prepared with the double emulsion/solvent evaporation technique. The effect of three parameters on the encapsulation efficiency has been determined: the role of the pH of the internal and external aqueous phases, the nature of the organic solvent and the effect of three different poly(lactide-co-glycolide) (PLGA) co-polymers. Particle size, zeta potential and release kinetics were also determined. The encapsulation efficiency varied from 4 to 83% reaching the maximum value when both the internal and the external water phases were brought to pH 7 (isoelectric point of the peptide), methylene chloride was used as solvent of the copolymers and PLGA rich in free carboxylic groups was employed. The release profiles obtained with this co-polymer were characterized by the absence of burst effect. This behavior as well as the high encapsulation efficiency was explained by an ionic interaction occurring between the peptide and the co-polymer. This supports the already expressed theory that the release of peptides and proteins from PLGA nanospheres is also governed by the affinity of the encapsulated molecule versus the polymer. The obtained nanoparticles, regarding their size, amount encapsulated and zeta potential, were shown to be suitable for transdermal iontophoretic administration.

Administration, Cutaneous↗
PubMed2001

Proteoglycan arrays in the cochlear basement membrane.

Indirect immunofluorescence and transmission electron microscopy were used to investigate the composition and assembly of proteoglycans in the basement membranes of the spiral limbus, basilar membrane, spiral ligament, Reissner's membrane, myelinated nerve fibers, and blood capillaries of the spiral ligament and stria vascularis in the chinchilla cochlea. Four types of basement membrane components: laminin, entactin/nidogen, type IV collagen and heparan sulfate proteoglycans were immunolocalized in all basement membranes in association with heparan sulfate proteoglycans. beta 1 and alpha 1 integrin subunits were also detected along these basement membranes. The concentration of the basement membrane-associated proteins and integrin subunits differed according to the adjacent cell type. Electron microscopy showed that all basement membranes, with exception of those of stria vascularis, consist of two layers: lamina lucida and lamina densa. In the stria vascularis only a homogeneous lamina densa was observed. Cuprolinic blue treatment revealed heterogeneity in the ultrastructure and arrangement of proteoglycans in the cochlear basement membranes. Proteoglycans of the subepithelial basement membrane in the spiral limbus and spiral ligament formed quasi-regular, linear arrays within the lamina lucida, or were located at both sides of the lamina densa in the basilar membrane and Reissner's membrane. In the basement membranes of nerve fibers, and capillaries in the spiral ligament and stria vascularis, proteoglycans were scattered throughout these basement membranes, but showed different concentration and ultrastructural appearance, which may be related to different filtration and mechanical properties. In the basilar membrane, PGs were located above and below the lamina densa. An additional layer of PGs below the lamina densa may function as increased mechanical support of organ of Corti by its interaction with underlying fibrillar collagen layer. In the stria vascularis capillaries, PGs were stained considerably less with Cuprolinic blue and were scattered through the lamina densa of the basement membrane compared to capillaries of spiral ligament. This observation is compatible with a higher permeability of the strial capillaries.

Animals↗
PubMed2001

Plasma and skin concentration of 5-methoxypsoralen in psoriatic patients after oral administration.

The aim of this work was to investigate the distribution of 5-methoxypsoralen in the skin after oral administration of the drug and to examine the correlation between skin and plasma concentrations. 5-Methoxypsoralen skin concentration was measured in both healthy and psoriatic sites of 10 psoriatic patients after single and multiple oral doses. The results obtained show that 5-methoxypsoralen accumulates at higher levels in the more external layers of the skin after oral administration. The high affinity of drug for the stratum corneum was confirmed by in vitro skin affinity measurements. The concentration of 5-methoxypsoralen in the skin was similar in both psoriatic and healthy sites, indicating that the pathology does not influence drug distribution in the skin. After single dose administration, a linear correlation was found between skin and plasma drug concentration. After multiple dose administration, drug concentration in the skin was fairly constant despite the variable plasma concentrations in different subjects.

5-Methoxypsoralen↗
PubMed2001

Increased activity and nuclear localisation of inositol lipid signal transduction enzymes in rat hepatoma cells.

To elucidate the relationship between inositol lipid signal transduction and oncogenic transformation, the activity and subcellular distribution of phospholipase C isoforms and of phosphatidylinositol 3-kinase were analysed in Morris hepatoma cells, MH(1)C(1), with respect to normal rat liver cells. The results provide evidence of a gain of function of the enzymes involved in inositide signal transduction, the amount of which increased mainly at the nuclear level. Phospholipase C and phosphatidylinositol 3-kinase activities are significantly higher in rat hepatoma than in rat liver cells. Moreover, some phospholipase C isoforms are expressed at higher levels at the nuclear level; this is particularly evident in the case of the delta 1 isoform which is not expressed at the nuclear level in rat liver cells. Therefore, the autonomous nuclear signal transduction system, formerly reported as involved in the modulation of cell proliferation and differentiation, appears also affected in oncogenic transformation.

Animals↗