A study of the potential of the pig as a model for the vaginal irritancy of benzalkonium chloride in comparison to the nonirritant microbicide PHI-443 and the spermicide vanadocene dithiocarbamate.
(9/45)
A porcine model was established to test the mucosal toxicity potential of a thiophene thiourea (PHI-443)-based anti-HIV microbicide and a vanadocene-based spermicide, vanadocene dithiocarbamate (VDDTC) in comparison to benzalkonium chloride (BZK). Nine domestic pigs (Duroc) in nonestrus stage received a single intravaginal application of 2% BZK, 2% PHI-443, or 0.1% VDDTC-containing gel. At various times after gel application, cell differentials and levels of inflammatory cytokines (IL-1beta, IL-4, IL-6, IL-8, IL-10, IL-18, IFN-gamma, and TNF-alpha) in cervicovaginal lavage (CVL) fluid were monitored by flow cytometry and ELISA, respectively. Eight pigs were exposed intravaginally to a gel with and without BZK or VDDTC for 4 consecutive days and vaginal tissues were scored histologically for inflammation using a new scoring system. Only CVL fluid from pigs exposed to BZK showed a significant increase of IL-1beta, IL-8, and also IL-18 production when compared to the controls, PHI-443 or VDDTC-treated groups. Maximum levels of BZK-induced IL-1beta (100-fold), IL-8 (2,500-fold), IL-18 (80-fold), and IFN-gamma (10-fold) were found at 24 hours. In the in vivo porcine vaginal irritation model, increased levels of vaginal IL-1beta, IL-8, and IL-18 were associated with histological changes consistent with vaginal inflammation. These results demonstrate that key cervicovaginal inflammatory cytokines are useful in vivo biomarkers for predicting the mucosal toxicity potential of vaginal products in the physiologically relevant and sensitive porcine model. (+info)
Modelling the human epidermis in vitro: tools for basic and applied research.
(10/45)
Culture models of tissues and organs are valuable tools developed by basic research that help investigation of the body functions. Modelling is aimed at simplifying experimental procedures in order to better understand biological phenomena, and consequently, when sufficiently characterized, culture models can also be utilized with high potential in applied research. In skin biology and pathology, the development of cultures of keratinocytes as monolayers has allowed the elucidation of most functional and structural characteristics of the cell type. Beside the multiple great successes that have been obtained with this type of culture, this review draws attention on several neglected characteristics of monolayer cultures. The more sophisticated models created in order to reconstruct the fully differentiated epidermis have followed the monolayers. The epidermal reconstruction produces all typical layers found in vivo and thus makes the model much less simple, but only this kind of model allows the study of full differentiation in keratinocyte and production of the cornified barrier. In addition to its interest in basic research, the reconstructed epidermis is currently gaining a lot of interest for applied research, particularly as an alternative to laboratory animals in the chemical and cosmetic industry. Today several commercial providers propose reconstructed skin or epidermis, but in vitro assays on these materials are still under development. In order to be beneficial at long term, the validation of assays must be performed on a material whose availability will not be interrupted. We warn here providers and customers that the longevity of in vitro assays will be guaranteed only if these assays are done with well-described models, prepared according to published procedures, and must consider having a minimum of two independent simultaneous producers of similar material. (+info)
Toxicity evaluation of chicken calamus keratin conduit as a tissue-engineering scaffold biomaterial.
(11/45)
OBJECTIVE: To evaluate the toxicity of chicken calamus keratin (CCK) conduit as a tissue-engineered scaffold material. METHODS: The chemical composition of the leaching solution of CCK was determined by means of ultraviolet spectrometry, and the toxic effects of the solution was evaluated by skin sensitization test in rats, intracutaneous stimulation test in rabbits, acute systemic toxicity test in mice, and cytotoxicity test in L929 cells. RESULTS: The leaching solution of CCK consisted mainly of middle-molecular-weight peptides with a small quantity of macromolecular proteins. Skin sensitization test in rats showed that application of the CCK leaching solution caused no obvious skin reddening, regional edema, or skin necrosis. Intracutaneous injection of the leaching solution in rabbits did not induce obvious skin stimulation manifested by intradermal erythema or edema. In acute systemic toxic test, administration of the leaching solution in mice caused no death, organ dysfunction, cyanosis, tremor, severe peritoneal irritation, ptosis, or dyspnoea. In vitro cytotoxicity test indicated that the cell toxicity of the CCK leaching solution was approximately at 0 level. CONCLUSION: CCK contained in the treated chicken calamus easily undergoes hydrolysis to release mainly some peptides which do not induce obvious toxic effects, suggesting the safe potential applications of CCK conduit as a tissue-engineering biomaterial. (+info)
Nanoemulsions as vehicles for transdermal delivery of aceclofenac.
(12/45)
Effect of iontophoresis and switching iontophoresis on skin accumulation of ketoprofen.
(14/45)
The effect of iontophoresis and switching iontophoresis on the skin accumulation of drugs was investigated. An acrylic diffusion cell mounted with electrode cells (bore: 2.2 cm) with circular platinum electrodes (diameter: 2.0 cm) was used for the skin accumulation study. The skin accumulation of fluorescein after non-switching and switching iontophoresis was macroscopically compared with that achieved by passive diffusion (control). Intense fluorescence was observed after the application of non-switching and switching iontophoresis. Furthermore, fluorescence was observed just under the electrode cell and hardly spread in the skin beyond the area of the electrode cell. The skin accumulation of ketoprofen after non-switching and switching iontophoresis was also compared with control data. Although non-switching iontophoresis showed the highest amount of ketoprofen accumulated in skin, skin irritation was observed. Among the various switching intervals, switching iontophoresis using 10-min intervals achieved the highest value, and there was no skin irritation. Furthermore, the amount of ketoprofen accumulated was maintained after switching iontophoresis at 10-min intervals up to 180 min. Since the amount of ketoprofen in skin after switching iontophoresis was greater than that after intermittent iontophoresis, switching iontophoresis should increase the amount of ketoprofen due to enhancement of skin penetration by skin hydration. These findings suggest that switching iontophoresis using an optimal switching interval can prevent skin irritation and enhance drug accumulation in the skin. (+info)
In vivo evaluation of a transdermal codrug of 6-beta-naltrexol linked to hydroxybupropion in hairless guinea pigs.
(15/45)