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The Human Nail: Structure, Properties, Therapy and Grooming
Published in Heather A.E. Benson, Michael S. Roberts, Vânia Rodrigues Leite-Silva, Kenneth A. Walters, Cosmetic Formulation, 2019
Kenneth A. Walters, Majella E. Lane
The application of nail polish remover to the nail will dissolve residual nitrocellulose and also remove lipids. These products generally consist of large amounts of organic solvents, with small amounts of oils. The solvents used are typically acetone, butyl acetate, ethyl acetate or ethoxyethanol; representative oils include castor oil or lanolin oil. Formulations may also include dyes, fragrances, preservatives, vitamins and UV absorbers (de Groot et al., 1994).
The Rat
Published in Francis L. S. Tse, James M. Jaffe, Preclinical Drug Disposition, 2017
Francis L. S. Tse, James M. Jaffe
Following drug administration, the rat is placed in a special metabolism cage (Fig. 3.14). Using a vacuum pump, a constant flow of room air (approx. 500 ml/min) is drawn through a drying column containing anhydrous calcium sulfate (Drierite®) impregnated with a moisture indicator (cobalt chloride), and passed into a second column containing Ascarite® II, where it is rendered carbon dioxide free. The air is then drawn in through the top of the metabolism cage. Exhaled breath exiting the metabolism cage is passed through a carbon dioxide absorption tower, where the expired 14CO2 is trapped in a solution such as a mixture of 2-ethoxyethanol and 2-aminoethanol (2:1). The trapping solution is collected, replaced with fresh solution, and assayed at designated times postdose so that the total amount of radioactivity expired as labeled carbon dioxide can be determined. The design of the cage shown in Fig. 3.14 also allows periodic collection of urine and feces without removing the rat from the cage.
Reproductive and Developmental Toxicity Studies by Cutaneous Administration
Published in Rhoda G. M. Wang, James B. Knaak, Howard I. Maibach, Health Risk Assessment, 2017
Rochelle W. Tyl, Raymond G. York, James L. Schardein
Neither the monobutyl ether (butylcellosolve) nor the monoethyl ether acetate forms of ethylene glycol were teratogenic in rats administered high doses on gestational days 7 to 16.105 In fact, no developmental toxicity occurred with the former, but increased resorption and decreased fetal body weight were seen with the latter. Similar, if not more extensive, developmental toxicity occurred in this species when the chemical was administered by inhalational exposure.111 The monoethyl ether (ethoxyethanol, EGEE) and monomethyl ether (methylcellosolve, EGME) forms of ethylene glycol were developmentally toxic. The first, EGEE applied dermally at doses of 0.25 or 0.5 ml/animal four times daily on gestational days 7 to 16 to rats, induced cardiovascular malformations, increased the incidence of some skeletal variations, and increased embryonic resorption at doses that were only slightly toxic to the mothers.112,113 These findings were essentially replicated in an inhalational study of EGEE in both rats and rabbits.114 EGME induced similar findings. Two separate studies, one in which 0.25 to 1 ml EGME was applied dermally on gestation days 7 to 16, and the other in which the chemical was applied at 500 to 2000 mg/kg on single days (10 to 14) during gestation, resulted in multiple malformations, increased resorption, and depressed fetal weights with only transient maternal weight loss the day after administration.40,43,115 In addition, EGME was dermally applied undiluted at 150 to 600 mg/kg/day or diluted with water at 37 to 300 mg/kg/d on gestational days 7 to 16 in rats; maternal and developmental toxicity was observed with postnatal loss and visceral and skeletal abnormalities at higher incidence after exposure to EGME in water.116 EGME was also shown to have predictable developmental toxicity in the rat from dermal administration in a short-term assay.117 An important consideration from a risk assessment perspective in these studies with EGME is that the developmental toxicity observed in these studies occurred in the presence of only slight or no maternal toxicity, making it hazardous from the developmental perspective.
Metabolism and disposition of the SGLT2 inhibitor bexagliflozin in rats, monkeys and humans
Published in Xenobiotica, 2020
Wenbin Zhang, Xiaoyan Li, Haifeng Ding, Yuan Lu, Geoff E. Stilwell, Yuan-Di Halvorsen, Ajith Welihinda
Rats were delivered [14C]-bexagliflozin at a target dose level of 3 mg kg−1 (135 μCi [5 MBq] kg−1). For analysis of excreta the urine and faeces from three animals individually housed in glass metabolic cages were collected up to 120 h post-dose. At the time of faecal collection, the cages were washed with water to collect any residual radioactivity. After aqueous washing, each cage was rinsed with methanol, and the methanol wash separately subjected to analysis. Faeces were homogenised in water. Any cage debris was collected on a daily basis to be pooled by animal over the entire period of collection. Because all the input radioactivity was recovered from the excreta, the cage debris samples were not analysed. Expired CO2 was collected into 2 serial solvent traps containing a CO2 absorbing solution of 2-ethoxyethanol: ethanolamine, 7:3 (v/v). Collections of expired air were discontinued at 48 h post-dose, after it was established that <0.5% of the dose was recovered in the previous 24 h collection period. For pharmacokinetic sampling, serial blood specimens (∼200 µL) were drawn from the tail vein and transferred into K3EDTA tubes at pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 h post-dose. Samples were thoroughly mixed and placed on wet ice prior to centrifugation at ∼4 °C within 1 h of collection, and the plasma was removed for analysis. For analysis of metabolites, nine animals were dosed and cohorts of three each underwent euthanasia and exsanguination at 0.5, 2 and 8 h post-dose.
Extended release formulations using silk proteins for controlled delivery of therapeutics
Published in Expert Opinion on Drug Delivery, 2019
Burcin Yavuz, Laura Chambre, David L Kaplan
As minimally invasive transdermal delivery systems, microneedles have been explored and silk showed significant success as a microneedle material with relatively simple fabrication methods like 3D printing or mold casting. Silk microneedles were prepared by casting silk solutions in polydimethylsiloxane (PDMS) molds [91]. Tetracycline and horseradish peroxidase (HRP) were loaded in the casting process as a small and large molecule. An in vitro gelatin hydrogel skin model was used to study the release kinetics and 48 h of release was achieved, and the released molecules had preserved bioactivity. The mechanical functions were also tested with mice to confirm skin penetration of the microneedles (Figure 2(c)) [91]. Swellable microneedles were also designed using 2-ethoxyethanol modified silk fibroin to enhance transdermal drug release [137]. These microneedles transformed into semi-solid hydrogels upon application to the skin. Transdermal delivery of FITC-dextran showed that higher swelling ratios correlated with higher transdermal release kinetics due to the larger pore sizes [137]. Silk microneedles have also been a focus for transdermal vaccine delivery. Vaccine coated silk microneedles were tested against influenza, C. difficile and Shigella on mice [138]. Microneedles were applied on mouse skin for 24 h for initial dosing and a booster dose followed 2 weeks later, and successful vaccination was achieved against all three antigens [138]. Another approach was to design silk/poly(acrylic acid) (PAA) microneedles, where the PAA base rapidly dissolved following a brief application to deliver the initial vaccine dose; then, methanol-treated silk tips serve as vaccine depots in the skin for 2 weeks [139]. The immune response to the microneedles was significantly higher than when a single intradermal injection of the vaccine was used. The pharmaceutical industry has started investing in these types of silk-based microneedle systems; Vaxess, Inc., developed a silk microneedle platform called MIMIX™ for vaccine delivery that has received Phase II SBIR Funding for clinical studies [140].