TRANSDERMAL DELIVERY OF IRON
铁的透皮输送
基本信息
- 批准号:7897463
- 负责人:
- 金额:$ 6.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-05-01 至 2012-04-30
- 项目状态:已结题
- 来源:
- 关键词:Adverse effectsAnemiaAzoneBiological AvailabilityChemicalsChild health careChildhoodDataDevelopmentDiseaseDoseDrug Delivery SystemsEnhancersGastrointestinal tract structureGlycineHealthIontophoresisIronIron deficiency anemiaLaboratoriesLeadLightLipid PeroxidesMeasuresMediatingMethodsModelingMolecular WeightMyristatesNatureOralOral AdministrationOxidative StressPatientsPenetrationPhysiologicalPlasmaPolyethylene GlycolsPregnancyPropertyRattusReportingRouteSaltsSkinSodium ChlorideStomachStudy SectionSystemTechniquesTherapeuticToxic effectTransdermal substance administrationabsorptionage groupdensityferric pyrophosphateflexibilitygastrointestinalimprovedpregnant
项目摘要
DESCRIPTION (provided by applicant): Iron deficiency is one of the most prevalent and serious health issues among people all over the world. The oral or parenteral iron supplements are administered to restore the iron stores in the body. Bioavailability of iron from the gastrointestinal tract is unpredictable and parenteral route do not allow frequent administration due to its invasiveness. Transdermal route is a noninvasive and patient compliant route of drug delivery that offers several advantages including precise dose delivery and reduced side effects. However, orally administered iron salts cannot be administered via transdermal route as they are known to release of free iron which in turn leads to increased oxidative stress. Parenteral iron forms cannot be administered due to their huge colloidal size. Ferric pyrophosphate (FPP) is the only low molecular weight iron salt that has been demonstrated to be safe for parenteral administration due to its high stability constant. However, due its hydrophilic nature it is poorly permeable across the skin. We hypothesize that therapeutically required amounts of iron could be delivered via transdermal route using appropriate skin permeation enhancement techniques. Three specific aims have been proposed to assess our hypothesis. In Aim 1 we propose to study the effect of selected chemical permeation enhancers on the transdermal delivery of FPP. We propose to study the effect of concentration of the selected enhancers and their combinations on the transdermal delivery of FPP. The successful completion of this specific aim will help us to identify the most effective penetration enhancers that could be incorporated in the transdermal iron therapeutic system. The preliminary studies demonstrated the feasibility of iontophoretic transdermal delivery of FPP. We strongly believe that the combination of appropriate chemical permeation enhancer with iontophoresis will result in transdermal delivery of therapeutically required amounts of iron at a relatively less current density (~0.3 mA/cm2 as opposed to 0.5mA/cm2 used in the preliminary studies). In Aim 2, we propose to investigate the effect of chemical permeation enhancers on the iontophoretic transdermal delivery of FPP. In Aim 3, we propose to evaluate the transdermal iron delivery systems in pregnant and non-pregnant anemic rat models. The toxicity of FPP will also be assessed by measuring the lipid peroxides in rat plasma. The successful completion of the above specific aims will result in the development of the first transdermal iron delivery systems which are likely to be more acceptable by patients of all age groups.
描述(申请人提供):缺铁是全世界最普遍和最严重的健康问题之一。口服或静脉注射铁补充剂是为了恢复体内储存的铁。来自胃肠道的铁的生物利用度是不可预测的,而且由于其侵袭性,非肠道途径不允许频繁给药。透皮给药途径是一种非侵入性和患者依从性的给药途径,具有几个优点,包括精确的剂量传递和减少副作用。然而,口服铁盐不能通过经皮途径给药,因为众所周知,它们会释放游离铁,进而导致氧化应激增加。注射用铁形态由于其巨大的胶体尺寸而不能给药。焦磷酸铁(FPP)是唯一已被证明是安全的低分子量铁盐,由于其高稳定常数而被证明是安全的。然而,由于其亲水性,它对皮肤的渗透性很差。我们假设,治疗所需的铁量可以通过适当的皮肤渗透促进技术通过经皮途径输送。已经提出了三个具体目标来评估我们的假设。在目的1中,我们建议研究选定的化学渗透促进剂对FPP透皮吸收的影响。我们建议研究所选择的促进剂及其组合的浓度对FPP透皮吸收的影响。这一特定目标的成功完成将有助于我们确定最有效的渗透促进剂,这些促进剂可以被纳入透皮铁治疗系统。初步研究证实了FPP离子导入透皮给药的可行性。我们坚信,将适当的化学渗透促进剂与离子导入相结合,将以相对较小的电流密度(约0.3 mA/cm2,而不是初步研究中使用的0.5 mA/cm2)将治疗所需数量的铁通过皮肤传递。在目的2中,我们建议研究化学渗透促进剂对FPP离子导入透皮吸收的影响。在目的3中,我们建议在妊娠和非妊娠贫血大鼠模型中评价经皮铁给药系统。FPP的毒性也将通过测定大鼠血浆中的过氧化脂质来评估。上述具体目标的成功完成将导致开发出第一个透皮铁质输送系统,该系统可能更容易为所有年龄段的患者所接受。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Sathyanarayana N Murthy其他文献
Sathyanarayana N Murthy的其他文献
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Impact of Formulation Composition on the Structure and Performance Attributes of Topical Products
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$ 6.93万 - 项目类别:
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