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PubMed2000

Heterogeneity of bone lamellar-level elastic moduli.

Advances in our ability to assess fracture risk, predict implant success, and evaluate new therapies for bone metabolic and remodeling disorders depend on our understanding of anatomically specific measures of local tissue mechanical properties near and surrounding bone cells. Using nanoindentation, we have quantified elastic modulus and hardness of human lamellar bone tissue as a function of tissue microstructures and anatomic location. Cortical and trabecular bone specimens were obtained from the femoral neck and diaphysis, distal radius, and fifth lumbar vertebra of ten male subjects (aged 40-85 years). Tissue was tested under moist conditions at room temperature to a maximum depth of 500 nm with a loading rate of 10 nm/sec. Diaphyseal tissue was found to have greater elastic modulus and hardness than metaphyseal tissues for all microstructures, whereas interstitial elastic modulus and hardness did not differ significantly between metaphyses. Trabecular bone varied across locations, with the femoral neck having greater lamellar-level elastic modulus and hardness than the distal radius, which had greater properties than the fifth lumbar vertebra. Osteonal, interstitial, and primary lamellar tissues of compact bone had greater elastic moduli and hardnesses than trabecular bone when comparing within an anatomic location. Only femoral neck interstitial tissue had a greater elastic modulus than its osteonal counterpart, which suggests that microstructural distinctions can vary with anatomical location and may reflect differences in the average tissue age of cortical bone or mineral and collagen organization.

Adult↗
PubMed2007

Effect of matrix elasticity on affinity binding and release of bioparticles. Elution of bound cells by temperature-induced shrinkage of the smart macroporous hydrogel.

The first step of bacterial or viral invasion is affinity and presumably multisite binding of bioparticles to an elastic matrix like a living tissue. We have demonstrated that model bioparticles such as inclusion bodies (spheres of about 1 microm in size) Escherichia coli cells (rods 1 x 3 microm), yeast cells (8 microm spheres), and synthetic microgel particles (0.4 microm spheres) are binding via different affinity interactions (IgG antibody-protein A, sugar-lectin, and metal ion-chelate) to a macroporous hydrogel (MH) matrix bearing appropriate ligands. The elastic deformation of the MH results in the detachment of affinity bound bioparticles. The particle detachment on elastic deformation is believed to be due to multipoint attachment of the particles to affinity matrix and the disturbance of the distance between affinity ligands when the matrix is deformed. No release of affinity bound protein occurred on elastic deformation. The efficiency of the particle release by the elastic deformation depends on the density of the ligands at the particle surface as well as on the elasticity of the matrix for relatively large particles. The release of the particles occurred irrespectively of whether the deformation was caused by external forces (mechanical deformation) or internal forces (the shrinkage of thermosensitive macroporous poly-N-isopropylacrylamide hydrogel on increase in temperature).

Concanavalin A↗
PubMed1997

The effect of actin filament compliance on the interpretation of the elastic properties of skeletal muscle fibres.

Recently, X-ray diffraction studies provided direct evidence for an appreciable length change in the actin filament upon activation. This finding has profound implications on the interpretation of the elastic properties of skeletal muscle fibre. In this study we determined the compliance of the actin filament during activation, using the data obtained previously from quick stretch and release experiments on skeletal muscle fibres of the frog. The effects of filament compliance are demonstrated clearly in the elastic properties of partially activated fibres. The low-frequency elasticity increases linearly with tension, reflecting an increase in the number of force-producing cross-bridges. At higher frequencies, this linearity is lost. In this study we describe the data consistently in terms of a cross-bridge stiffness increasing linearly with tension and a constant Young's modulus for the actin filament of 44 MN m-2. This corresponds to a compliance of 23 pm microns-1 per kN m-2 tension developed. Using this value for the actin filament Young's modulus, its contribution to the elastic properties of skeletal muscle fibre of the frog is considered in rigor and relaxation. The filament compliance hardly affects the overall elasticity of the muscle fibre in relaxation. In contrast, it contributes to a large extent to the overall elasticity in rigor. Taking account of the filament compliance, we find that the Young's modulus in rigor exhibits an increase from 14 MN m-2 at frequencies below 500 Hz to 55 MN m-2 above 40 kHz.

Actins↗
PubMed2002

Elastic flexural properties of multistranded stainless steel versus conventional nickel titanium archwires.

Based on a recent investigation that modeled the elastic properties (ie, strength, stiffness and range) of multistranded wires made from linearly elastic materials, three-stranded (triple) and six-stranded coaxial (coax) stainless steel (SS) wires were compared to single-stranded (single) SS and conventional nickel titanium (NiTi) leveling wires. To measure Young's modulus of elasticity (E), flexural tests were performed with an Instron mechanical testing machine in a three-point bending arrangement having a span length of 8.9 mm or 12.5 mm. A strong correlation between wire stiffness and the area moment of inertia demonstrated that strand interaction was negligible at low activations and that E = 199 GPa was constant even for the heavily drawn coax strands. Using the Instron with an extensometer, the 0.1% yield strengths (sigma(YS)) of the single SS wires and the straight inner strands within the coax wires were tested. The ratio of the sigma(YS) to the ultimate tensile strength averaged 0.81 for the single wires, 0.88 for the coax wires, and was subsequently assigned 0.85 for the triple wires. The average sigma(YS) values were 1.88, 1.83, and 1.78 GPa for the single, triple, and coax SS wires, respectively. For each NiTi wire, both the sigma(YS) and the elastic limit (sigma(EL)) via cyclic loading were measured. The conventional NiTi wires displayed nonlinear elasticity, as the average sigma(EL) values (1.10 GPa) were 50% higher than the average sigma(YS) values (0.73 GPa). Compared to the elastic properties of the conventional NiTi wires, the triple and coax SS wires generally matched the stiffness, but had only one-third to one-half of the strength and range. Since the properties of strength and range are both proportional to sigma(YS), fabrication using alloys with enhanced sigma(YS) values would allow multistranded SS archwires to compete better against conventional NiTi products.

Dental Alloys↗
PubMed1999

Elastic fibres in the vesicourethral junction and urethra of the guinea pig: quantification with computerised image analysis.

Elastic fibres, which are intimately associated with collagen, a major component of the urethra, have been assumed to contribute to the resting urethral closure pressure. The Miller stain for elastin was used to demonstrate elastic fibres in cryostat sections of guinea pig bladder base, vesicourethral junction (VUJ) and urethra. Computerised image analysis was employed to objectively quantify these fibres. Both male and female guinea pigs showed significantly greater amounts of circularly disposed elastic fibres in the VUJ than in the other 2 regions examined. This particular disposition of fibres may be responsible for imparting resiliency and plasticity to the VUJ, allowing it to distend and recoil repeatedly in response to urine outflow. Furthermore, the elastic fibres may be partly responsible for the passive occlusive force in this region. Elastic fibres in the distal urethra were not quantified because of their relative paucity. Sagittal sections of the urethra revealed a mass of longitudinally arranged elastic fibres localised almost exclusively within the mucosa, submucosa and longitudinal smooth muscle layer. Functionally, this arrangement may exist to facilitate urethral length changes that occur in micturition.

Animals↗
PubMed2003

Relation between the elastic properties and intima-media thickness of the common carotid artery.

The purpose of the study was to describe the relation between wall elasticity and intima-media thickness in the human carotid artery prior to the development of atherosclerotic plaques. Fifty-eight apparently healthy men, aged 42-65 years (mean 55 years), without symptoms of cardiovascular disease were studied. Thickness and elastic properties of the common carotid artery wall were assessed using ultrasonography and non-invasive arterial pressure measurements. The relation between the calculated intima-media area and the pressure strain elastic modulus was positive and statistically significant on the right but not on the left side. No statistically significant relations were found between the calculated intima-media area and the stiffness or between the intima-media thickness and the elastic modulus or stiffness on either side. Thus, the relations between the common carotid artery intima-media thickness/calculated intima-media area and the common carotid artery elastic modulus/stiffness are weak. In regions without atherosclerotic plaques, the elastic properties of the human carotid artery wall do not seem to be influenced by the wall thickness in an important way.

Adult↗
PubMed2000

Elastic fiber proteins in the glomerular mesangium in vivo and in cell culture.

BACKGROUND: Glomerular capillaries of the mammalian kidney are exposed to high intraluminal hydrostatic pressures and require elastic constraint to maintain size, shape, and integrity. Previous morphological and functional studies indicated that the extracellular matrices of glomeruli, that is, basement membrane and mesangial matrix, contribute to glomerular resilience and mechanical stability. Immunofluorescence microscopy findings demonstrated elastic fiber components to be located in the renal vasculature, including glomeruli. The aim of this study was to clarify the exact glomerular localization, composition, and cellular production of these proteins. METHODS: We examined the renal distribution of the elastic fiber proteins fibrillin-1, emilin, microfibril-associated glycoproteins (MAGPs) 1 and 2, latent transforming growth factor-binding protein-1 (LTBP-1), and elastin using immunohistology and immunoelectron microscopy of human, rat, and mouse kidneys. In mesangial cell cultures, we also studied the expression and extracellular deposition of such proteins by use of Northern blotting and immunocytochemistry. RESULTS: Fibrillin-1, emilin, MAGPs 1 and 2, and LTBP-1 were present in glomeruli of mouse, rat, and human kidney, where they were located predominantly in the mesangial extracellular matrix underlying glomerular endothelium and basement membrane. Several of these proteins, as well as elastin, were also expressed in the renal vasculature. While elastin localized to the glomerular vascular pole in afferent and efferent arterioles extending to Bowman's capsule, it was not found in the glomerular capillary tuft. Cultured mesangial cells of rat, mouse, and human kidneys expressed mRNAs of fibrillin-1, emilin, MAGP-2, and elastin, and the respective proteins localized within and outside of mesangial cells, as shown by immunocytochemistry. mRNA expression of fibrillin-1, emilin, and elastin was strong in quiescent mesangial cells; their gene expression was further up-regulated by transforming growth factor-beta1, while it was transiently reduced when cells were exposed to mitogenic 10% fetal calf serum and platelet-derived growth factor. CONCLUSIONS: These findings demonstrate that specific elastic fiber proteins are produced and secreted by mesangial cells. This process is regulated by growth factors. Their abundance in the extracellular matrix of the mesangium is in keeping with the concept that elastic fiber proteins contribute to the mechanical stability and elastic strength of the glomerular capillary tuft.

Animals↗
PubMed2002

Elastic properties of irradiated RBCs measured by optical tweezers.

BACKGROUND: Gamma irradiation of RBCs results in the production of reactive oxygen capable of initiating the process of membrane lipid peroxidation and accelerates the leakage of potassium ions from RBCs, resulting in an increase of internal viscosity. STUDY DESIGN AND METHODS: The elastic properties of irradiated and stored RBC units were studied using laser optical tweezers. The laser trapped the cell and the membrane elasticity was analyzed, measuring the cell deformation in six different drag velocities. Five RBC units were split into two portions. One portion received a gamma irradiation dose of 25 Gy, and the second one was used as a control and was not irradiated. All units were stored (4 degrees C), and the elasticity was examined on Days 1, 14, 21, and 28. RESULTS: Elastic properties (mu) from irradiated RBCs stored for 21 and 28 days were significantly affected compared with control cells (21 days: control, 0.3 +/- 0.03 x 10(-3); irradiated, 3.5 +/- 1.3 x 10(-3) dyn/cm; p < 0.001; and 28 days: control, 0.5 +/- 0.09 x 10(-3); irradiated, 14 +/- 3.2 x 10(-3) dyn/cm; p < 0.001). CONCLUSION: The sensitivity of the laser optical tweezers method showed that there is no significant change in elasticity over time for up to 14 days of storage, regardless of whether the unit was irradiated or not. However, beyond 21 days of storage, irradiated units demonstrate decreased elasticity.

Adult↗
PubMed2001

Histochemical study of the elastic fibers in pathologic human temporomandibular joint discs.

PURPOSE: This study investigated histochemically the elastic fibers in human temporomandibular joint (TMJ) discs with varying degrees of tissue degeneration/regeneration to determine whether there are differences that correlate with the histologic findings. MATERIALS AND METHODS: Ten diseased human TMJ discs and 2 control specimens were studied histochemically by staining with Weigert's resorcin-fuchsin after oxidation with peracetic acid. This technique selectively stains elastic, elaunin, (pre-elastic), and oxytalan fibers. RESULTS: In TMJ discs with an abnormal collagen fiber arrangement, an increased number of oxytalan fibers could be observed, contrary to discs with scar-like tissue transformation in which oxytalan fibers were decreased in number. In discs showing tears and clefts, the oxytalan fibers run perpendicular to the defects, whereas elaunin and elastic fibers were mainly circumferentially arranged. In discs with chondroid metaplasia, elastic, elaunin, and oxytalan fibers were extensively detected. CONCLUSIONS: It is hypothesized that the elastic, elaunin, and oxytalan fibers found in severely damaged discs appear to ensure biomechanical compliance by reinforcing regions devoid of collagen bundles and thus function as shock absorbers of stretch and compression.

Adult↗
PubMed2003

Biaxial flexural strength, elastic moduli, and x-ray diffraction characterization of three pressable all-ceramic materials.

STATEMENT OF PROBLEM: Before the release of an advanced ceramic material, independent assessment of its strength, elastic modulus, and phase composition is necessary for comparison with peer materials. PURPOSE: This study compared the biaxial flexural strength, elastic moduli, and crystalline phases of IPS Empress and Empress 2 with a new experimental ceramic. MATERIAL AND METHODS: Twenty standardized disc specimens (14 x 1.1 mm) per material were used to measure the biaxial strength. With a universal testing machine, each specimen was supported on 3 balls and loaded with a piston at a crosshead speed of 0.5 mm/min until fracture. Three standardized bars (30 x 12.75 x 1.1 mm) for each material were prepared and excited with an impulse tool. The resonant frequencies (Hz) of the bars were used to calculate the elastic moduli with the equation suggested by the standard ASTM (C 1259-94). X-ray diffraction with Cu Kalpha at a diffraction angle from 20 to 40 degrees was used to identify the crystalline phases by means of a diffractometer attached to computer software. The data were analyzed with 1-way analysis of variance followed by pairwise t tests (P<.05). RESULTS: Mean biaxial strengths were 175 +/- 32, 407 +/- 45, and 440 +/- 55 MPa for IPS Empress, Empress 2, and the experimental ceramic, respectively. Elastic modulus results were 65, 103, and 91 GPa for the same materials, respectively. There was no significant difference in strength and elastic modulus between Empress 2 and the experimental ceramic. Both materials demonstrated a significantly higher elastic modulus and strength than IPS Empress. X-ray diffraction revealed leucite as the main crystalline phase for IPS Empress and lithium disilicate for both Empress 2 and the experimental ceramic. CONCLUSION: Within the limitations of this study, the improved mechanical properties of Empress 2 and experimental ceramic over those of IPS Empress were attributed to the nature and amount of their crystalline content lithium disilicate.

Aluminum Silicates↗
PubMed2002

Comparison of the endothelial surface and subjacent elastic lamina of anterior descending coronary arteries at the location of atheromatous lesions with internal thoracic arteries of the same subjects: a scanning electron microscopic study.

AIM: Current theories fail to explain the localisation of atheromatous lesions or their variable incidence in different arteries of the same subject. The objective of this study was to compare by scanning electron microscopy (SEM) the endothelial surface and the subjacent elastic lamina of human coronary arteries at the location of areas showing infiltration by lipid and cells, with the same components of internal thoracic arteries of the same subjects. METHODS: The endothelial surface and the subjacent elastic lamina of localised atheromatous areas of 146 anterior descending coronary arteries were compared with the same structural components of the internal thoracic arteries of the same subjects, using SEM, transverse paraffin sections and freeze-fracture. Some arteries were digested with formic acid to destroy the endothelium and interstitial tissue, and reveal the elastin fibre structure of the elastic laminae. RESULTS: Coronary arteries showed localised defects of the endothelial surface and of the elastin fibre structure of the subjacent elastic membrane, with the presence of lipid and cells in transverse sections of the intima. Internal thoracic arteries showed such changes only rarely, more particularly in older age groups. CONCLUSIONS: In localised areas of the coronary arteries showing infiltration of the wall by lipid and cells, there were imperfections of the endothelial surface and of the elastin fibre structure of the subjacent elastic lamina. These imperfections were not in general present in the endothelial surface, or subendothelial elastic lamina of the internal thoracic arteries in age groups below 50, and only rarely in older subjects.

Adolescent↗
PubMedDate not supplied

Granuloma annulare: an elastic tissue disease? Case report and literature review.

Granuloma annulare (GA) is a condition characterized by the presence of palisading granulomas usually in the dermis. Traditionally, the histopathological changes are described as consisting of focal degeneration of dermal collagen fibers. However, no convincing evidence for such alteration is found in the literature. A histopathological study was done to ascertain the nature of the dermal abnormality. Ten skin biopsies showing lesions of GA were studied by light and electron microscopy. On light microscopy, all lesions showed focal dermal degeneration with near total loss of elastic fibers. Ultrastructural examination in nine cases demonstrated degenerated elastic fibers with loss of peripheral microfibrils and abnormal elastic matrix. The degenerated elastic fibers were surrounded by intact collagen fibers. These findings show that the main alteration in GA is elastic fiber degeneration and strongly suggest that the primary target leading to the development of this disorder is injury to the elastic tissue.

Adult↗
PubMed1969

The elastic fiber. I. The separation and partial characterization of its macromolecular components.

The two morphologically different constituents of the mature elastic fiber, the central amorphous and the peripheral microfibrillar components, have been separated and partially characterized. A pure preparation of elastic fibers was obtained from fetal bovine ligamentum nuchae by extraction of the homogenized ligament with 5 M guanidine followed by digestion with collagenase. The resultant preparation consisted of elastic fibers which were morphologically identical with those seen in vivo. The microfibrillar components of these elastic fibers were removed either by proteolytic enzymes or by reduction of disulfide bonds with dithioerythritol in 5 M guanidine. The microfibrils solubilized by both methods were rich in polar, hydroxy, and sulfur-containing amino acids and contained less glycine, valine, and proline than the amorphous component of the elastic fiber. In contrast, the amino acid composition of the amorphous component was identical with that previously described for elastin. This component demonstrated selective susceptibility to elastase digestion, but was relatively resistant to the action of other proteolytic enzymes and to reduction. These observations establish that the microfibrils consist of a different connective tissue protein (or proteins) that is neither collagen nor elastin. During embryologic development the microfibrils form an aggregate structure before the amorphous component is secreted. These microfibrils may therefore play a primary role in the morphogenesis of the elastic fiber.

Amino Acids↗
PubMed2004

Regulation of sodium channel function by bilayer elasticity: the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol.

Membrane proteins are regulated by the lipid bilayer composition. Specific lipid-protein interactions rarely are involved, which suggests that the regulation is due to changes in some general bilayer property (or properties). The hydrophobic coupling between a membrane-spanning protein and the surrounding bilayer means that protein conformational changes may be associated with a reversible, local bilayer deformation. Lipid bilayers are elastic bodies, and the energetic cost of the bilayer deformation contributes to the total energetic cost of the protein conformational change. The energetics and kinetics of the protein conformational changes therefore will be regulated by the bilayer elasticity, which is determined by the lipid composition. This hydrophobic coupling mechanism has been studied extensively in gramicidin channels, where the channel-bilayer hydrophobic interactions link a "conformational" change (the monomer<-->dimer transition) to an elastic bilayer deformation. Gramicidin channels thus are regulated by the lipid bilayer elastic properties (thickness, monolayer equilibrium curvature, and compression and bending moduli). To investigate whether this hydrophobic coupling mechanism could be a general mechanism regulating membrane protein function, we examined whether voltage-dependent skeletal-muscle sodium channels, expressed in HEK293 cells, are regulated by bilayer elasticity, as monitored using gramicidin A (gA) channels. Nonphysiological amphiphiles (beta-octyl-glucoside, Genapol X-100, Triton X-100, and reduced Triton X-100) that make lipid bilayers less "stiff", as measured using gA channels, shift the voltage dependence of sodium channel inactivation toward more hyperpolarized potentials. At low amphiphile concentration, the magnitude of the shift is linearly correlated to the change in gA channel lifetime. Cholesterol-depletion, which also reduces bilayer stiffness, causes a similar shift in sodium channel inactivation. These results provide strong support for the notion that bilayer-protein hydrophobic coupling allows the bilayer elastic properties to regulate membrane protein function.

Adaptation, Physiological↗
PubMed2007

In vivo areal modulus of elasticity estimation of the human tympanic membrane system: modelling of middle ear mechanical function in normal young and aged ears.

The quasi-static elastic properties of the tympanic membrane system can be described by the areal modulus of elasticity determined by a middle ear model. The response of the tympanic membrane to quasi-static pressure changes is determined by its elastic properties. Several clinical problems are related to these, but studies are few and mostly not comparable. The elastic properties of membranes can be described by the areal modulus, and these may also be susceptible to age-related changes reflected by changes in the areal modulus. The areal modulus is determined by the relationship between membrane tension and change of the surface area relative to the undeformed surface area. A middle ear model determined the tension-strain relationship in vivo based on data from experimental pressure-volume deformations of the human tympanic membrane system. The areal modulus was determined in both a younger (n = 10) and an older (n = 10) group of normal subjects. The areal modulus for lateral and medial displacement of the tympanic membrane system was smaller in the older group (mean = 0.686 and 0.828 kN m(-1), respectively) compared to the younger group (mean = 1.066 and 1.206 kN m(-1), respectively), though not significantly (2p = 0.10 and 0.11, respectively). Based on the model the areal modulus was established describing the summated elastic properties of the tympanic membrane system. Future model improvements include exact determination of the tympanic membrane area accounting for its shape via 3D finite element analyses. In vivo estimates of Young's modulus in this study were a factor 2-3 smaller than previously found in vitro. No significant age-related differences were found in the elastic properties as expressed by the areal modulus.

Adult↗
PubMed2003

Tissue engineering by cocultivating human elastic chondrocytes and keratinocytes.

To date, there is no optimal way to reconstruct an external ear in cases of microtia or after trauma or burns damaging the external ear. However, success in the area of tissue engineering has indicated that autologous elastic cartilage produced in vitro might be of great importance in the future treatment of these patients. In the present study we have engineered human, elastic cartilage in vitro by culturing chondrocytes in fibrin glue. Furthermore, the engineered elastic cartilage was seeded with human keratinocytes to investigate the possibility of combining these two tissues into one integrated structure. Histological analysis and immunohistochemistry were done every second week for 10 weeks. The elastic chondrocytes were shown to grow well in the matrix and proliferated in a dense pattern. After 10 weeks a matrix containing elastin was shown by staining with orcein, indicating that an elastic cartilage had been formed. The seeded keratinocytes adhered to the cartilage, proliferated, and formed a stratified epidermal layer, which was shown by routine histological staining and immunohistochemistry. This study shows that human elastic chondrocytes can be cultured in fibrin glue and that human keratinocytes can be cocultured with this engineered cartilage, which might be of great importance in future reconstruction of ears.

Biomarkers↗
PubMed1995

Molecular analysis of elastic properties of the stratum corneum by solid-state 13C-nuclear magnetic resonance spectroscopy.

To elucidate the precise molecular mechanisms underlying stratum corneum (SC) elasticity, we investigated the molecular dynamics of chemical residues within keratin fibers of human plantar SC under various conditions by cross polarization/magic angle spinning 13C-nuclear magnetic resonance. The intensities of nuclear magnetic resonance spectra responsible for amide carbonyl, C alpha methine, and side-chain aliphatic carbons in the intact SC decreased markedly with increasing water content of up to 30% in dry SC, and then remained constant at greater than 30%. Lipid extraction of intact SC with acetone/ether (1:1) did not induce any significant change in the nuclear magnetic resonance spectrum, whereas additional treatment with water, which released natural moisturizing factors (mainly amino acids), caused the SC to lose elasticity. The observed decrease in elasticity of the SC recovered after treatment with basic and neutral amino acids, but not after treatment with acidic amino acid. With the latter treatment, movement of amino acid molecules was significantly disturbed, suggesting a strong interaction with keratin fibers. Parallel studies of the complex elastic modulus of a pig SC sheet with a rheovibron also demonstrated that removal of natural moisturizing factor reduced the elasticity of the SC; this effect was also reversed by the application of basic and neutral amino acids, but not by the application of acidic amino acid. These findings suggest that structural keratin proteins, mainly consisting of 10-nm filaments, acquire their elasticity with the help of hydrated natural moisturizing factor via the reduction of intermolecular forces, probably through nonhelical regions between keratin fibers.

Amino Acids↗
PubMed2004

Quantitative assessment of the transport of elastic and rigid vesicle components and a model drug from these vesicle formulations into human skin in vivo.

The aim of this study was to quantitatively assess the distribution profiles of elastic and rigid vesicle material in human skin in vivo. Furthermore, the distribution profiles of the model drug ketorolac applied in these vesicle formulations was investigated. A deuterium-labelled phospholipid was incorporated into these vesicles to serve as a marker for the vesicle material. The vesicles were loaded with ketorolac at saturated concentrations. Vesicle solutions were applied non-occlusively onto the skin and the treated site was sequentially tape-stripped. Tape-strips were analyzed for vesicle material using attenuated total reflectance-Fourier transform infrared spectroscopy and for ketorolac by extraction of the tape-strips followed by high pressure liquid chromatography. Distribution profiles in the stratum corneum (SC) were obtained for the elastic and rigid vesicle material and for the ketorolac. These profiles have suggested that elastic vesicle material can rapidly enter the deeper layers of the SC and can reach almost the SC-viable epidermal junction. Rigid vesicle material, however, did not penetrate deep into the SC. Furthermore, the elastic vesicles were better than the rigid vesicles in the enhancement of ketorolac transport into human SC. The distribution profile of ketorolac in the deeper SC layers was, however, different from that of the vesicle material. This suggests that once the elastic vesicles partition into the SC, the ketorolac is released from the vesicles. The elastic vesicles are superior to the rigid vesicles both in terms of vesicular transport into the SC and in terms of therapeutic potential as a skin delivery vehicle.

Administration, Cutaneous↗