Date of Award

8-2012

Document Type

Thesis

Degree Name

Master of Science (MS)

Legacy Department

Bioengineering

Advisor

Alexis, Frank

Committee Member

LaBerge , Martine

Committee Member

Wei , Yanzhang

Abstract

Bone is a form of mineralized connective tissue that provides strength and rigidity to the skeleton. The two primary components within bone tissue are an organic extracellular matrix, containing type I collagen, and an inorganic mineral component composed mainly of calcium phosphate hydroxyapatite crystals. Over time the microarchitecture of bone can break down due to a variety of different factors, mainly the onset of osteoporosis in post-menopausal women, Paget's disease, and the experience of a loss of gravity during space flight. Currently there are about ten million people in the United States alone suffering from osteoporosis.
The prevention of further damage as well as the replacement of lost bone tissue is the focus of many therapeutic approaches. A large number of available treatments rely on the concept of blocking further bone loss by inhibiting the natural resorption process. Bisphosphonates are the most popular drug therapy in this category. But there are many other treatments that strive to prevent further bone resorption such as hormone therapy, estrogen agonist / antagonists, calcitonin, and denosumab. Other therapies approach the problem of bone loss by inducing the formation of new bone tissue to replace that lost to these pathologies. These include teriparatide, strontium ranelate, and statins, which are the focus of this research.
The goal of this research was to formulate a targeted nanoparticle drug delivery system for the treatment of bone diseases. A hydroxyapatite nanoparticle conjugated with poly(glycolic acid)-poly(ethylene glycol) diblock copolymer was created to deliver statin drugs. These drugs act as competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, for the lowering of serum cholesterol. Recently, statins have been investigated for their ability to induce bone formation by enhancing expression of bone morphogenic protein-2.
In addition to formulation, studies were completed to prove the particle's low toxicity, loading abilities, and release pharmacokinetics. In order to enhance the specificity with which these particles are delivered to bone, targeting peptides were tested for in vitro and in vivo targeting efficiency and exclusivity.

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