Date of Award
2015
Document Type
Dissertation
Degree Name
Ph.D. in Pharmaceutical Sciences
Department
Pharmaceutics and Drug Delivery
First Advisor
Narasimha S. Murthy
Second Advisor
Samir A. Ross
Third Advisor
Bonnie A. Avery
Relational Format
dissertation/thesis
Abstract
Iron is an integral part of hemoglobin and essential for the production of red blood cells. Iron deficiency and the resulting anemia are major nutritional deficiency disorders. The majority of patient populations suffering from iron deficiency anemia (IDA) are women of child bearing age and children of all ages. Iron deficiency is a complication of various other chronic conditions. Oral iron salts or colloidal parenteral iron formulations are treatment options for iron replenishment since several decades, but they are associated with severe side effects along with other patient noncompliance issues. Transdermal delivery of iron could be a potential alternative to treat iron deficiency due to safety and offers more acceptability. Since conventional iron formulations are not suitable for transdermal delivery, quest for an ideal iron compound resulted in identification of soluble Ferric Pyrophosphate (FPP), which was demonstrated to be very stable and safe for parenteral administration. Passive delivery of FPP was not successful due to its high molecular weight (745 Da) and low lipid solubility. Transdermal delivery of FPP using chemical permeation enhancers, iontophoresis, microneedle pretreatment and combination of these techniques were evaluated and proved to be successful in delivering iron across the skin. When iontophoresis was combined with microneedle pretreatment, adequate iron could be delivered in anemic rat models to reverse the iron deficiency. Further, a safe and patient friendly iron delivery system was developed by incorporating FPP in soluble microneedles. In vitro and in vivo studies were carried out to evaluate the FPP release and dermal kinetic profile of the iron from the soluble microneedles. Safety and toxicity of FPP in human skin cell lines was also investigated. The feasibility of transdermal delivery of Iron-dextran was also evaluated. Passive delivery of iron dextran is impossible due to its high molecular weight. Microneedle assisted delivery of iron dextran was investigated and soluble microneedle system with iron dextran was developed. Overall, the results of the project suggest that transdermal delivery of iron could be a potential alternate to treat IDA. Iron replenishment via transdermal route is likely to be more effective and safer than the conventional routes of administration.
Recommended Citation
Modepalli, Naresh, "Novel Delivery Systems For Iron Replenishment" (2015). Electronic Theses and Dissertations. 732.
https://egrove.olemiss.edu/etd/732
Concentration/Emphasis
Emphasis: Pharmaceutics