Design and Development of pH Sensitive Nanomedicine for Targeted Drug Delivery

Date of Award

2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Institution Granting Degree

University of Rhode Island

Cedarville University School or Department

Science and Mathematics

First Advisor

Oleg A. Andreev

Abstract

Targeted drug delivery has been the major topic in drug formulation and delivery. As nanomedicine emerges to create nano-scale therapeutics and diagnostics, it is still essential to embed targeting capability to these novel systems to make them useful. Design of robust nanomedicine with universal targeting capabilities could provide effective solutions to the ever increasing demand of curing and preventing major diseases.

Diseases like carcinoma & ischemia are accompanied with hypoxia and acidosis. Because of the elevated glycolysis and acidosis in the diseased cells, they show a lower pH in the surface of the cells which promotes the appearance of aggressive malignant cells with enhanced multidrug resistance. Therefore, the extracellular acidity can be used as a hallmark to target and deliver nanotheranostics. Thus coating nanoparticles with pH (Low) Insertion Peptides (pHLIPs) increase efficiency of targeting acidic diseased tissues. This novel method could be used as a promising method to create future nanotheranostics for cancer and other diseases which are dominating the present world.

The main goal of the work presented here is to

  • Review the field of advanced targeted nanmedicine and its future trends;
  • Design pHLIP® coated lipid & surfactant based nanovesicles to deliver therapeutic and diagnostic agents;
  • Use different drugs and dyes for imaging and therapy;
  • Assess the cytotoxicity, targeting capabilities and the cellular interaction of these nanovesicles in in-vitro and in-vivo.

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