Munt Daniel J, Grana Anne, Hulce Martin, Fusaro Ramon M, Dash Alekha K
Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, Omaha, Nebraska, USA.
Department of Chemistry, Creighton University, Omaha, Nebraska, USA.
AAPS PharmSciTech. 2015 Dec;16(6):1425-33. doi: 10.1208/s12249-015-0335-8. Epub 2015 May 19.
Unprotected sunlight exposure is a risk factor for a variety of cutaneous cancers. Topically used dihydroxyacetone (DHA) creates, via Maillard reaction, chemically fixed keratin sunscreen in the stratum corneum with significant protection against UVA/Soret radiation. When used in conjunction with naphthoquinones a naphthoquinone-modified DHA Maillard reaction is produced that provides protection across the UVB/UVA/Soret spectra lasting up to 1 week, resisting sweating and contact removal. The aim of this study was to examine a simplified version of this formulation for effect on UV transmission and to determine if penetration levels merit toxicity concerns. Permeability was demonstrated for freshly prepared DHA (30 mg/mL) and lawsone (0.035 mg/mL) alone and in combination using a side-by-side diffusion apparatus at 37°C over 48 h across shed snake skin and dermatomed pig skin. These samples were then examined for effectiveness and safety. Concentrations were determined by HPLC and UPLC monitored from 250-500 nm. Lawsone flux significantly decreased across pig skin (20.8 (± 4.8) and 0.09 (± 0.1) mg/cm(2) h without and with DHA, respectively) but did not change across shed snake skin in the presence of DHA. Significantly reduced lawsone concentration was noted in donor chambers of combined solutions. Damage was not observed in any skins. Darker coloration with greater UV absorbance was observed in skins exposed to the combined solution versus individual solutions. This study confirmed that combined DHA and lawsone provided effective blocking of ultraviolet light through products bound in keratinized tissue. DHA permeation levels in pig skin suggest further in vitro and in vivo study is required to determine the safety of this system.
无防护的阳光照射是多种皮肤癌的危险因素。局部使用的二羟基丙酮(DHA)通过美拉德反应在角质层中产生化学固定的角蛋白防晒霜,对UVA/索雷特辐射有显著防护作用。当与萘醌联合使用时,会产生萘醌修饰的DHA美拉德反应,可在UVB/UVA/索雷特光谱范围内提供长达1周的防护,能抵抗出汗和接触清除。本研究的目的是检验该配方的简化版本对紫外线透射的影响,并确定渗透水平是否值得关注毒性问题。使用并排扩散装置在37°C下,对新鲜制备的单独的DHA(30mg/mL)和紫铆因(0.035mg/mL)以及它们的组合,在48小时内透过蛇蜕皮肤和猪皮进行渗透性测试。然后对这些样品进行有效性和安全性检测。通过HPLC测定浓度,并在250 - 500nm范围内进行UPLC监测。紫铆因在猪皮上的通量显著降低(分别在无DHA和有DHA时为20.8(±4.8)和0.09(±0.1)mg/cm²·h),但在有DHA的情况下,蛇蜕皮肤上的通量没有变化。在混合溶液的供体室中,紫铆因浓度显著降低。在任何皮肤中均未观察到损伤。与单独溶液相比,暴露于混合溶液的皮肤颜色更深,紫外线吸收率更高。本研究证实,DHA和紫铆因组合通过结合在角质化组织中的产物有效地阻挡了紫外线。猪皮中DHA的渗透水平表明,需要进一步进行体外和体内研究以确定该系统的安全性。