J A Bouwstra

..Based on the results of this and previous studies we offer an explanation for the deviation in lipid organization in diseased and in dry skin compared to normal skin...

..Hydrogels based on HyPG have great potential as drug delivery matrices and for tissue engineering purposes...

..Our results show that HSEs can be used as a model to study the water distribution...

..In conclusion, our studies demonstrate that barrier disruption due to acetone treatment is mainly due to removal of corneocytes...

..Only topical application of water induced marked swelling of corneocytes. This clearly shows that the stratum corneum water level in HSE is regulated by other, still unknown, factors, in addition to NMF...

..The changes in stratum corneum morphology with increasing water level have also been observed in dermatomed skin...

..Finally, the information on the role various lipid classes play in lipid phase behavior has been used to interpret the changes in lipid organization and barrier properties of diseased skin...

..From this we conclude that the results obtained with lipid mixtures can be used to predict the SC lipid organization in native tissue...

..From our results we can conclude that the lipid mixtures prepared at pH 5 resemble more closely the lipid phase behaviour in intact SC than the lipid mixtures prepared at pH 7.4...

..In the second part of this paper the possible interactions between vesicles and skin are described, focusing on differences between the effects of gel-state vesicles, liquid-state vesicles and elastic vesicles...

..These changes in phase behavior might be due to a larger amount of linoleic acid moiety in HCER mixtures compared with that in pigCER mixtures...

..Finally a new model, the "sandwich model", will be proposed that describe the localisation of the fluid phases in the stratum corneum...

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..The current findings suggest that beta-alanine-5-OH-DPAT is a promising prodrug, with a good balance between stability, transport efficiency and enzymatic conversion...

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..In mixtures with sebaceous lipids, the presence of the hexagonal lattice increased. These findings provide a basis for the mechanism by which these enhancers and sebaceous lipids interact with human SC lipids...

..Furthermore, while the majority of the lipids form a crystalline packing, the linoleate moiety of the acylCERs participates in a "pseudo fluid" phase...

..In this study, modulation of the immune response against diphtheria toxoid (DT) by various adjuvants in transcutaneous immunization (TCI) with microneedle array pretreatment was investigated...

..Extrapolating these findings to the situation in stratum corneum led us conclude that in stratum corneum, fatty acids and CER participate in the orthorhombic lattice at 32 degrees C, the skin temperature...

..As far as structural changes in stratum corneum are concerned iontophoresis is therefore a safe method at the experimental conditions we used...

..CONCLUSIONS: The transdermal iontophoresis challenges the skin barrier function and induces transient mild skin irritation, but does not cause any permanent damage to the skin when applied for 3 h at a current density of 0.25 mA cm(-2)...

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..The scattering length density profile of the 5.4-nm phase containing this deuterated ceramide demonstrated a symmetric arrangement of the ceramides with interdigitating acyl chains in the center of the unit cell...

..The enhanced elasticity might contribute to an optimal design of vesicles as drug carriers for transdermal application...

..Only a mixture containing synthetic CER1 and CER3, CHOL and FFA showed similar phase behaviour to that of SC...

..1 nmol/cm2 h) compared to the control patients (iontophoresis without absorption enhancers). In five out of eight patients in the study group and in three out of eight patients in the control group, clinical improvement was observed...

..However, some degradation was also observed for FITC-Dex and DCB. We conclude that assembled microneedle arrays can be used to deliver compounds through the skin up to a molecular weight of at least 72 kDa...

..This demonstrates that the lipid mixtures serve as an excellent model for the lipid organization in SC, not only with respect to the repeat distance, but also in terms of the electron density distribution within the unit cell...

..The presence of iodide inside corneocytes suggests the possibility of transcellular percutaneous iodide transport...

..In conclusion, we demonstrated that VC properties adjust to the fundamental change from the intrauterine to the post-natal environment...

..The results suggest a lower degree of ordering of VC lipids as compared to the SC. A small-angle X-ray diffraction study showed similar results...

..In the second part of this paper, the possible interactions between vesicles and skin are described, focusing on differences between the effects of gel-state, liquid-state, and elastic vesicles...

..Finally, using freeze fracture electron microscopy, changes in the lamellar organization in stratum corneum of both patient groups could be observed...

..The label applied non-occlusively in flexible liposomes penetrated deeper into the skin than after occlusive application...

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..c. by wide-angle X-ray diffraction. After lipid extraction, such diffraction patterns could no longer be detected in the samples...

..On the basis of these observations, a molecular model for the 14.7 nm phase has been proposed in which the lipids are organized in a lamellar phase with three different lipid layers in a symmetric unit cell...

..However, a single application of 3 h is probably too short to exert increased hydration as measured with ATR-FTIR...

..Furthermore, the formation of the 13-nm lamellar phase is not very sensitive to variations in the total CER level, which is similar to the in vivo situation...

..The observed changes in the ultrastructure of the stratum corneum can explain the increased R-apomorphine transport during iontophoresis...

..These results indicate that TCI of DT and CT with microneedle treatment results in comparable protection as injection of DT-alum, and TCI of influenza vaccine adjuvanted with CT is superior to the injection of plain vaccine...

..Especially the thermotropic stabilization of the orthorhombic lateral packing, which might reduce water loss from the skin, is considered to contribute to the moisturizing effect of IPIS and ISIS in stratum corneum...

..In conclusion, lipid mixtures prepared with well-defined synthetic ceramides offer an attractive tool with which to unravel the importance of the molecular structure of individual ceramides for proper lipid organization...

..These results show that the presented cell culture method can be utilized to generate HSEs under submerged conditions to study epidermal formation under aqueous conditions...

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..Summarizing, SC cells are not equally sensitive to moisturizer application: centrally located corneocytes are more sensitive than corneocytes in the upper and the lowest regions of the SC...

..The maximum Flux(ss) achieved was around 80 nmol cm(-2) h(-1) indicating that by means of iontophoresis, a therapeutic level of rotigotine might be achieved with a reasonable patch size...

..It is essential that drug molecules are applied together with and entrapped within the vesicles themselves, suggesting that elastic vesicles act as drug carrier systems and not solely as penetration enhancers...

..0 micromol x cm(-2) h(-1) demonstrating the potential of the iontophoretic delivery of this dopamine agonist for the symptomatic treatment of Parkinson's disease...

..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...

..The purpose of this study was to gain insight into the delivery and immunogenicity of N-trimethyl chitosan (TMC) adjuvanted diphtheria toxoid (DT) formulations applied transcutaneously with microneedles...

..However, no conclusion can be drawn about the actual route of transport to the hair follicle...

..Elastic vesicles and micelles demonstrated very different interactions with human skin and hence probably also have different mechanisms of action for the enhancement of drug transport...

..This opens the opportunity for dermal and transdermal delivery of drugs and vaccines...

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..Therefore we conclude that targeting to the hair follicle can be increased by the use of lipophilic drugs in combination with surfactant solutions and propylene glycol...

..It was found that high concentrations of glycerol change the lamellar organization slightly, while domains with an orthorhombic lateral packing are still observed...

..The optimal lipid mixture was evaluated on tape-stripped hairless mouse skin in vivo. The rate of barrier recovery was increased and comparable to VC lipid treatment...

..CONCLUSIONS: Both pH and NaCl concentration of the donor phase are crucial on the iontophoretic transport of rotigotine. Electro-repulsion is the main mechanism of the iontophoretic transport of rotigotine...

..CONCLUSIONS: The developed in vitro models demonstrated their strength and consistency to describe the drug transport during and post-iontophoresis...

..In order to increase the number of drugs administered via the transdermal route, novel drug delivery systems have to be designed. Among these systems are iontophoresis, electroporation, microneedles, and vesicular systems...

..Thus, based on this in vitro study, transdermal iontophoretic delivery of 5-OH-DPAT is very promising...

..Assuming a one to one in vitro/in vivo correlation the Timolol transport in vitro results in therapeutic plasma concentrations in humans with very low current densities limiting possible skin irritation...

..The method has the potential to access deeper skin layers as well as to visualize diffusion processes in cells...

..Based on the results obtained, a mechanism of action for the elastic vesicles was proposed...

..This demonstrates that TMC functions as an immune potentiator for antigens delivered via the skin...

..Moreover, comparison of transport data through shed snake skin with human stratum corneum indicates that both shunt- and intercellular pathways are involved in the iontophoretic transport of R-apomorphine...

..The transdermal iontophoretic delivery of a novel series of 2- aminotetralins and chromanamine-based dopamine agonists was investigated in vitro...

..Furthermore, we have proposed a hypothesis that the channel-like regions represent imperfections within the intercellular lipid lamellae in areas with highly undulating cornified envelopes...

..This information can be used to determine penetration pathways in the skin...

..A linear relationship between current density and R-apomorphine flux indicates that the iontophoretic delivery combined with surfactant pretreatment allows a controlled and individualised administration of R-apomorphine...

..In conclusion, the linomat method was chosen as the preferred method for preparing the substitute...

..This compartmental modeling approach provides a scientific basis to examine in vitro-in vivo correlations of drug transport by iontophoresis...

..DT-vesicles formulated at pH 4.5 were stable and showed high association of DT with preserved antigenicity, and are therefore excellent candidates for future in vivo studies...

..In case of a non-lethal PDT, fungal re-growth started on the remnants of the treated mycelium...

..6 +/- 2.3 ng/ (h*cm2). This was a 6.2-fold increase compared to the most rigid vesicles. CONCLUSIONS: This study supports the hypothesis that elastic vesicles are superior to rigid vesicles as vehicles for transdermal drug delivery...

..rubrum when using red light...

..A considerable dopaminergic effect was achieved, indicating the feasibility to reach therapeutically effective concentrations of 5-OH-DPAT upon transdermal iontophoresis...