Cytotoxicity,in Vivo Skin Irritation and Acute Systemic Toxicity of the Mesoporous Magnesium Carbonate Upsalite^(█)

Upsalite®is a mesoporous magnesium carbonate synthesized without using surfactants and therefore highly attractive from environmental and production economy points of view. The material has recently been suggested as drug delivery vehicle and as topical bacteriostatic agent. In order to continue exploring these and other bio-related applications of the material, primary biocompatibility studies are needed. Herein we present the first in vivo acute systemic toxicity and skin irritation analyses as well as in vitro cytotoxicity evaluations of Upsalite®. The material was found to be non-toxic for human dermal fibroblasts cells up to a concentration of 1000 μg/ml and 48 h exposure in contrast to the mesoporous silica material SBA-15, used as reference, which significantly affected cell viability at particle concentration of 500 and 1000 μg/ml after the same exposure time. Topical application of Upsalite®resulted in negligible cutaneous reactions in a rabbit skin irritation model and no evidence of significant systemic toxicity was found when saline extracts of Upsalite®were injected in mice. Injection of sesame oil extract, however, resulted in transient weight loss, most likely due to injection of particles, and not toxic leachables. The presented results form the basis for future development of Upsalite®and similar mesoporous materials in biomedical applications and further toxicity as well as biocompatibility studies should be directed towards specific areas of use.

Needle-free injection of insulin powder: delivery efficiency and skin irritation assessment

Insulin is widely used in treating diabetes, but still needs to be administered by needle injection. This study investigated a new needle-free approach for insulin delivery. A portable powder needleless injection（PNI） device with an automatic mechanical unit was designed. Its efficiency in delivering insulin was evaluated in alloxan-induced diabetic rabbits. The skin irritation caused by the device was investigated and the results were analyzed in relation to aerodynamic parameters. Inorganic salt-carried insulin powders had hypoglycemic effects, while raw insulin powders were not effective when delivered by PNI, indicating that salt carriers play an important role in the delivery of insulin via PNI. The relative delivery efficiency of phosphate-carried insulin powder using the PNI device was 72.25%. A safety assessment test showed that three key factors（gas pressure, cylinder volume, and nozzle distance） were related to the amount of skin irritation caused by the PNI device. Optimized injection conditions caused minimal skin lesions and are safe to use in practice. The results suggest that PNI has promising prospects as a novel technology for delivering insulin and other biological drugs.

In Vitro Assessment of Irritation Potential of an Anti-Melanogenic Agent,PF3758309,in a Reconstructed Human Epidermis Model

Purpose:This study was designed to determine whether a novel anti-melanogenic agent,PF3758309,has the potential to cause acute cutaneous irritation using a human skin equivalent model (HSEM).Methods:Human skin equivalent was constructed through incubation of normal human derived epidermal keratinocytes (HEKs)on collagen matrix insert with proliferation media.Using constructed human skin equivalent,the irritation potential of PF3758309 were investigated whether the viability of this agent-treated HESM is under 50%(irritant)or not (non-irritant)using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay after applying the agent to the epidermal surface of the HSEM.Also,the PF3758309-mediated anti-pigmentation effects were analyzed using Fontana-Masson staining in the HSEM.Results:The integrity of the constructed HSEM was confirmed using immunohistochemical staining with differentiation markers of epidermis,and observed that Keratin 5,Keratin I and Involucrin were stained in basal,supra-basal and granular layers,respectively.In vitro irritation assay showed that the mean viabilities of the PF3758309 was 83.6%,78.8%and 77.8%at the treatment doses of 0.2,0.5 and I mg,respectively;however,the mean viability of the positive control (5%sodium dodecyl sulfate)-treated HESM was 2.8%.Also,in vitro corrosion assay showed that the mean viabilities of the PF3758309 was 95.3%,95.0%and 94.2% at the treatment doses of 0.2,0.5 and 1 mg,respectively.Furthermore,using a Fontana-Masson staining assay,the melanin levels in the PF3758309-treated HSEM was significantly decreased compared with the levels in control HSEM.Conclusion: The anti-melanogenic agent,PF3758309,has no skin irritation potential under the conditions used in this study.

Technical Approaches and in-vitro Evaluation Methods for Scalp Care

Scalp care is important in maintaining good conditions of scalp and hair. Key technical approaches for scalp care include reducing the chance of scalp inflammation, improving scalp defense, and activating hair follicle cells. As the cosmetics industry is moving toward to alternative methods to animal testing based on the 3 Rs(Replacement, Reduction and Refinement), in vitro methods will be widely used to evaluate the effects of scalp care. In this paper, we describe the detailed technical approaches for scalp care and the in vitro evaluation methods for skin irritation, anti-inflammation, barrier function, blood circulation, hair growth and male pattern hair loss prevention, respectively.

Graphene Oxide/Lauryl Betaine Nano Material Synthesis and Properties

This paper aims at synthesizing a detergent with graphene oxide(GO)and lauryl betaine(LB),where the GO will have a better performance with the modification of LB.First,the complexus of GO and LB and the complexus of GO,KH550(Amino functional silane),and LB were synthesized to obtain two products,GO⁃LB and GO⁃KH550⁃LB.Then,the abilities and safety of the products were evaluated by characterization,contact angle measurement,measurement of KRAFFT Point,foaming test,emulsion ability test,decontamination capacity test,skin irritation test,and skin allergy test.Results of the experiment showed that GO⁃LB was superior to GO⁃KH550⁃LB in wetting ability and foaming stability,while GO⁃KH550⁃LB outperformed in emulsifying capacity.Besides,good abilities of removing mussels,seaweed,and protein were proved.According to the result of the irritation test of the materials to skin,they were both at the light irritation level,and the irritation of the GO⁃LB was slightly lower than that of GO⁃KH550⁃LB.Neither GO⁃LB nor GO⁃KH550⁃LB had allergic effect.Therefore,it can be concluded that as a surface active agent,graphene oxide/lauryl betaine was effective as a new detergent,which had low irritation and insignificant allergic phenomena on the human body over a long term of use.

Development and application of a novel method to assess exposure levels of sensitizing and irritating substances leaching from menstrual hygiene products

Menstrual hygiene products(MHPs)like tampons,sanitary towels and panty liners are widely used by women and come in close contact with the intimate parts of the human body,which consist of mucosae that lack the important barrier function of normal skin.Hence,substances leaching from MHP can easily penetrate and become systemically available.This study aims to develop a new in chemico methodology that allows to identify and measure realistic consumer exposure levels of several skin sensitizers and irritants leaching from MHPs under simulated use conditions.To assess the leaching of chemicals from MHPs,a menstrual fluid simulant(MFS)simulating pH,osmolarity and protein binding was first established.Subsequently,an analytical methodology was developed for nine well-known skin sensitizers and skin irritants.In short,the MFS samples underwent salting-out assisted liquid-liquid extraction before ultra-high performance liquid chromatography coupled with a triple-quadrupole mass spectrometry analysis.Validation was performed according to the total error approach with acceptability limits of±15%regarding the total analytical error(including systematic and random bias).Fifteen commercially available MHPs were assessed.Six products were found to leach at least one of the following five sensitizing and irritating compounds:a-isomethyl ionone,benzyl salicylate,hexyl cinnamaldehyde,linalool and piperonal.Piperonal was the most abundant compound leaching from the MHPs,with leaching concentration levels measured to 28.22 mg/g.In addition,the leaching level of benzyl salicylate was found to be 11.03 mg/g.The latter fragrance concentration is above 10 mg/g and would trigger mandatory labelling if the Cosmetic Regulation would apply for MHPs.However,none of the identified and quantified skin sensitizers were mentioned on the packaging.In conclusion,this novel methodology makes it possible to estimate realistic human exposure levels to skin sensitizers and irritants through the use of MHPs.Availability of these exposure estimates is vital to carry out a quantitative health risk assessment of these substances.