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71.
Z. Ding E. Van Riet S. Romeijn G. F. A. Kersten W. Jiskoot J. A. Bouwstra 《Pharmaceutical research》2009,26(7):1635-1643
Purpose 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.
Methods TCI was performed on BALB/c mice with or without microneedle array pretreatment using DT as a model antigen co-administrated
with lipopolysaccharide (LPS), Quil A, CpG oligo deoxynucleotide (CpG) or cholera toxin (CT) as adjuvant. The immunogenicity
was evaluated by measuring serum IgG subtype titers and neutralizing antibody titers.
Results TCI with microneedle array pretreatment resulted in a 1,000-fold increase of DT-specific serum IgG levels as compared to TCI.
The immune response was further improved by co-administration of adjuvants, showing a progressive increase in serum IgG titers
when adjuvanted with LPS, Quil A, CpG and CT. IgG titers of the CT-adjuvanted group reached levels comparable to those obtained
after DT-alum subcutaneous injection. The IgG1/IgG2a ratio of DT-specific antibodies decreased in the following sequence:
plain DT, Quil A, CT and CpG, suggesting that the immune response was skewed towards the Th1 direction.
Conclusions The potency and the quality of the immune response against DT administered by microneedle array mediated TCI can be modulated
by co-administration of adjuvants. 相似文献
72.
Rolf J. VerheulBram Slütter Suzanne M. BalJoke A. Bouwstra Wim JiskootWim E. Hennink 《Journal of controlled release》2011,156(1):46-52
The physical stability of polyelectrolyte nanocomplexes composed of trimethyl chitosan (TMC) and hyaluronic acid (HA) is limited in physiological conditions. This may minimize the favorable adjuvant effects associated with particulate systems for nasal and intradermal immunization. Therefore, covalently stabilized nanoparticles loaded with ovalbumin (OVA) were prepared with thiolated TMC and thiolated HA via ionic gelation followed by spontaneous disulfide formation after incubation at pH 7.4 and 37 °C. Also, maleimide PEG was coupled to the remaining thiol-moieties on the particles to shield their surface charge.OVA-loaded TMC/HA nanoparticles had a size of around 250-350 nm, a positive zeta potential and OVA loading efficiencies up to 60%. Reacting the thiolated particles with maleimide PEG resulted in a slight reduction of zeta potential (from + 7 to + 4 mV) and a minor increase in particle size. Stabilized TMC-S-S-HA particles (PEGylated or not) showed superior stability in saline solutions compared to non-stabilized particles (composed of nonthiolated polymers) but readily disintegrated upon incubation in a saline buffer containing 10 mM dithiothreitol. In both the nasal and intradermal immunization study, OVA loaded stabilized TMC-S-S-HA particles demonstrated superior immunogenicity compared to non-stabilized particles (indicated by higher IgG titers). Intranasal, PEGylation completely abolished the beneficial effects of stabilization and it induced no enhanced immune responses against OVA after intradermal administration. In conclusion, stabilization of the TMC/HA particulate system greatly enhances the immunogenicity of OVA in nasal and intradermal vaccination. 相似文献
73.
Gai Ling Li Ronald van der Geest Laurence Chanet Elske van Zanten Meindert Danhof Joke A Bouwstra 《Journal of controlled release》2002,84(1-2):49-57
To achieve a therapeutical effect of the anti-Parkinson's drug R-apomorphine via iontophoresis delivery, enhancement strategies in vitro were explored using three structurally related enhancers, lauric acid (LA), dodecyltrimethylammonium bromide (DTAB) and Laureth-3 oxyethylene ether (C(12)EO(3)). Human stratum corneum and shed snake skin were pretreated with 0.15 M each enhancer solution in propylene glycol (PG). Thereafter, passive diffusion, iontophoretic transport and post-iontophoretic passive diffusion were investigated. Compared to the control (PG pretreatment), a slight inhibition on both passive and iontophoretic delivery was observed with cationic surfactant DTAB pretreated stratum corneum. Pretreatment with anionic surfactant LA resulted in a great enhancement on passive delivery, but only a small enhancing effect on the iontophoretic delivery. Unlike the others, the nonionic surfactant C(12)EO(3) substantially increased iontophoretic transport rate of R-apomorphine by 2.3-fold, whereas passive delivery was basically unchanged or slightly affected. The magnitude of enhancing effect of C(12)EO(3) was dependent on the surfactant concentration and the pretreatment duration. 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. 相似文献
74.
Bouwstra JA Pilgram GS Ponec M 《The Journal of investigative dermatology》2002,118(5):897-8; author reply 899-901
75.
Pharmaceutical Research - 相似文献
76.
de Jager M Gooris G Ponec M Bouwstra J 《The Journal of investigative dermatology》2004,123(5):911-916
The lipid organization in the upper layer of the skin, the stratum corneum (SC), is important for the skin barrier function. This lipid organization, including the characteristic 13 nm lamellar phase, can be reproduced in vitro with mixtures based on cholesterol, free fatty acids and natural as well as synthetic ceramides (CER). In human SC, nine CER classes have been identified (CER1-CER9). Detailed studies on the effect of molecular structure of individual ceramides on the SC lipid organization are only possible with synthetic lipid mixtures, as their composition can be accurately chosen and systematically modified. In the present study, small-angle X-ray diffraction was used to examine the organization in synthetic lipid mixtures of which the synthetic ceramide fraction was prepared with sphingosine-based CER1 or phytosphingosine-based CER9. The latter acylceramide contains an additional hydroxyl group at the sphingoid backbone. The results show that a gradual increase in CER1 level consistently promotes the formation of the 13 nm lamellar phase and that partial replacement of CER1 by CER9 does not affect the phase behavior. Interestingly, complete substitution of CER1 with CER9 reduces the formation of the long periodicity phase and results in phase separation of CER9. 相似文献
77.
Guangsheng Du Laura Woythe Koen van der Maaden Mara Leone Stefan Romeijn Alexander Kros Gideon Kersten Wim Jiskoot Joke A. Bouwstra 《Pharmaceutical research》2018,35(10):189
Purpose
To examine the immunogenicity of diphtheria toxoid (DT) loaded mesoporous silica nanoparticles (MSNs) after coated and hollow microneedle-mediated intradermal immunization in mice.Methods
DT was loaded into MSNs and the nanoparticle surface was coated with a lipid bilayer (LB-MSN-DT). To prepare coated microneedles, alternating layers of negatively charged LB-MSN-DT and positively charged N-trimethyl chitosan (TMC) were coated onto pH-sensitive microneedle arrays via a layer-by-layer approach. Microneedle arrays coated with 5 or 3 layers of LB-MSN-DT were used to immunize mice and the elicited antibody responses were compared with those induced by hollow microneedle-injected liquid formulation of LB-MSN-DT. Liquid DT formulation with and without TMC (DT/TMC) injected by a hollow microneedle were used as controls.Results
LB-MSN-DT had an average size of about 670 nm and a zeta potential of ?35 mV. The encapsulation efficiency of DT in the nanoparticles was 77%. The amount of nano-encapsulated DT coated onto the microneedle array increased linearly with increasing number of the coating layers. Nano-encapsulated DT induced stronger immune responses than DT solution when delivered intradermally via hollow microneedles, but not when delivered via coated microneedles.Conclusion
Both the nano-encapsulation of DT and the type of microneedles affect the immunogenicity of the antigen.78.
Caussin J Groenink HW de Graaff AM Gooris GS Wiechers JW van Aelst AC Bouwstra JA 《Experimental dermatology》2007,16(11):891-898
To study the mode of action of moisturizers on human skin, hydrophilic moisturizers in water and neat lipophilic moisturizers were applied on excised skin for 24 h at 32 degrees C. Samples of the treated skin were subsequently visualized in a cryoscanning electron microscope. The stratum corneum (SC) appeared as a region of swollen corneocytes (the swollen region) sandwiched between two layers of relatively dry corneocytes (the upper and lower non-swelling regions respectively). Lipophilic moisturizers increased the water content of the SC, whereas hydrophilic moisturizers can also reduce the water content of the SC. When focusing on the effect of the moisturizers on the three different regions, it was observed that cells in the swelling region are most sensitive to the application of the moisturizers and that the change in SC thickness is most influenced by the change in the thickness of the swelling region. 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. 相似文献
79.
Chemical enhancement of percutaneous absorption in relation to stratum corneum structural alterations. 总被引:8,自引:0,他引:8
The outermost layer of the skin, stratum corneum (SC), provides an outstanding barrier against the external environment and is also responsible for skin impermeability toward most solutes. The barrier function is related to the unique composition of the SC lipids and their complex structural arrangement. The lipoidal matrix of the SC, therefore, is a target of penetration enhancer action. The literature on the skin barrier structure and function and on the mechanisms of action of some well established permeation promoters, with a focus on their impact on SC structural alterations, is reviewed. Data obtained from infrared, thermal, and fluorescence spectroscopic examinations of the SC and its components imply enhancer improved permeation of solutes through the SC is associated with alterations involving the hydrocarbon chains of the SC lipid components. Data obtained from electron microscopy and X-ray diffraction reveals that the disordering of the lamellar packing is also an important mechanism for increased permeation of drugs induced by penetration enhancers. 相似文献
80.
This paper reports the in vitro transport of pergolide from L-595-PEG-8-L elastic vesicle formulations. Several aspects of vesicular delivery were studied in order to elucidate the possible mechanisms of action and to establish the optimal conditions and drug candidates for usage with L-595-PEG-8-L elastic vesicles. All studies were performed using human skin and flow-through Franz diffusion cells. Pergolide was chosen as model drug. The findings show that there was a strong correlation between the drug incorporation to saturated levels and the drug transport, both of which were influenced by the pH of the drug-vesicular system. The optimal pH was found to be 5.0, giving the highest drug incorporation as well as the highest drug transport. Non-occlusive co-treatment with elastic vesicles improved the skin delivery of pergolide compared to the non-occlusive buffer control by more than 2-fold. However, non-occlusive pre-treatment of skin with empty vesicles did not enhance drug transport. Occlusion improved drug transport from both elastic vesicle as well as buffer solutions due to the fact that water is an excellent penetration enhancer for pergolide. However, in contrast to non-occlusive application, the action of the elastic vesicles themselves was diminished, as occlusive treatments with elastic vesicles showed a lower flux compared to occlusive treatment with the buffer control. Hence, the highest pergolide skin permeation in this study was obtained from an occluded saturated buffer solution, giving a steady-state flux of 137.9 ng/h cm(-2). The volume of application did not have any effect on the drug transport. In conclusion, these results showed no evidence that a penetration enhancing effect is the main mechanism of action. The pH of the drug-vesicular system is an important factor to consider when optimising elastic vesicle delivery systems. Occlusion reduces the actions of elastic vesicles, but could increase the pergolide transport since water is a good penetration enhancer for this particular drug. Based on the results obtained, a mechanism of action for the elastic vesicles was proposed. 相似文献