title: Transdermal Delivery of Iron Using Soluble Microneedles: Dermal Kinetics and Safety.
abstract: Currently, the iron compounds are administered via oral and parenteral routes in patients of all ages, to treat iron deficiency. Despite continued efforts to supplement iron via these conventional routes, iron deficiency still remains the most prevalent nutritional disorder all over the world. Transdermal replenishment of iron is a novel, potential approach of iron replenishment. Ferric pyrophosphate (FPP) was found to be a suitable source of iron for transdermal replenishment. The safety of FPP was assessed in this project by challenging the dermal fibroblast cells with high concentration of FPP. The cell viability assay and reactive oxygen species assay were performed. The soluble microneedle array was developed, incorporated with FPP and the kinetics of free iron in the skin; extracellular fluid following dermal administration of microneedle array was investigated in hairless rats. From the cell based assays, FPP was selected as one of the potential iron sources for transdermal delivery. The microneedles were found to dissolve in the skin fluid within 3 hours of administration. The FPP concentration in the dermal extracellular fluid declined after complete dissolution of the microneedle array. Overall, the studies demonstrated the safety of FPP for dermal delivery and the feasibility of soluble microneedle approach for transdermal iron replenishment therapy.
authors.affiliation: The University of Mississippi School of Pharmacy, Mississippi 38677.
authors.forename: Naresh
authors.initials: N
authors.lastname: Modepalli
authors.affiliation: Institute for Drug Delivery and Biomedical Research, Bangalore, India; KLE's University College of Pharmacy, Bangalore, India.
authors.forename: H Nanjappa
authors.initials: HN
authors.lastname: Shivakumar
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Maeliosa T C
authors.initials: MT
authors.lastname: McCrudden
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
authors.affiliation: College of Pharmacy, Mercer University, Atlanta, Georgia 30341.
authors.forename: Ajay
authors.initials: A
authors.lastname: Banga
authors.affiliation: The University of Mississippi School of Pharmacy, Mississippi 38677; Institute for Drug Delivery and Biomedical Research, Bangalore, India. Electronic address: murthy@olemiss.edu.
authors.forename: S Narasimha
authors.initials: SN
authors.lastname: Murthy
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D011756:Diphosphates / Q000008:administration & dosage* / Q000009:adverse effects*; D016503:Drug Delivery Systems / Q000009:adverse effects* / Q000379:methods; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007501:Iron / Q000008:administration & dosage* / Q000009:adverse effects*; D007700:Kinetics; D008845:Microinjections / Q000009:adverse effects / Q000379:methods; D009339:Needles / Q000009:adverse effects; D051381:Rats; D054772:Rats, Hairless; D017382:Reactive Oxygen Species / Q000378:metabolism; D012449:Safety; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*
chemical_list: D011756:Diphosphates; D017382:Reactive Oxygen Species; D007501:Iron; C049051:ferric pyrophosphate
keywords: cell lines; kinetics; microarrays; microdialysis; reactive oxygen species; skin; transdermal drug delivery