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.

Public Health Relevance

Transdermal delivery or Iron Project Narrative Iron deficiency is the most prevalent type of anemia which is generally treated by administration of oral or parenteral iron supplements. Absorption of iron from the gastrointestinal tract is highly unpredictable and is associated with several gastric side effects. Parenteral delivery is invasive and does not allow frequent administration. Transdermal delivery of iron offers several advantages including precise dose delivery and minimal gastric side effects. Therefore we propose to develop transdermal therapeutic systems for the delivery or iron.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Small Research Grants (R03)
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Pediatrics Subcommittee (CHHD)
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Taylor-Zapata, Perdita
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University of Mississippi
Schools of Pharmacy
United States
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Modepalli, Naresh; Shivakumar, H Nanjappa; McCrudden, Maeliosa T C et al. (2016) Transdermal Delivery of Iron Using Soluble Microneedles: Dermal Kinetics and Safety. J Pharm Sci 105:1196-200
Modepalli, Naresh; Jo, Seongbong; Repka, Michael A et al. (2013) Microporation and 'iron'tophoresis for treating iron deficiency anemia. Pharm Res 30:889-98
Sammeta, Srinivasa M; Repka, Michael A; Narasimha Murthy, S (2011) Magnetophoresis in combination with chemical enhancers for transdermal drug delivery. Drug Dev Ind Pharm 37:1076-82