Nanoformulation of drugs and use of microarray technology in cancer studies

Nano-delivery systems and microarray technology are fast-becoming fundamental approaches for innovative strategies in the prevention and treatment of diseases such as cancer. Nano-delivery systems and, in particular, nanoemulsions, can (1) convert fat soluble to water soluble compounds thereby allowing delivery into a polar versus non polar matrices potentially reducing toxicity and (2) reduce particle sizes of existing drugs that are usually 1000's of nm in size to less than 100 nm size In the process, the surface/volume ratios are increased and, therefore, bio-availability and efficacy of pharmaceuticals. Application of microarray technology enabled us to identify and quantify genetic alterations that occur in the development and progression of cancer cells. This technology also allowed us to better-understand the pathways that regulate proliferation by using E2F4, a nuclear protein transcription factor as a probe from the E2F family which regulates transcription in the mammalian cell cycle. Thus we were able to investigate certain aspects of the cancer process and the known mutations which disrupt normal cell proliferation, DNA synthesis and cell division.;Our primary goal was to describe, in detail, the main signaling or regulatory pathways operant in breast, skin and melanoma tumorogenesis. These pathways mainly regulate proliferation, apoptosis or cell death and differentiation. We investigated how individual pathways modulate susceptibility to typical drug therapy and compare them to our nanoemulsion preparation of these drugs and determined the multiple pathways which interact to alter malignant cells. We tested our hypotheses that nanoemulsion preparations of pharmaceuticals significantly increase their bioavailability and efficacy while reducing adverse side effects by addressing the following: (1) Using differentiated human cancer cell lines and immune-compromised mouse models to investigate the global changes, and associated consequences of specific anti-cancer chemotherapy drugs and compare them to our proprietary nanoemulsion formulations of these same drugs as it relates to bioavailability, and efficacy, including their ability to overcome the physical and electrostatic barriers that influence their permeability and toxicity. (2) Determining the transcriptional regulatory mechanism(s) controlling the cell cycle by (a) utilizing different human cancer cell lines in vivo and in vitro, incorporating micro-array technology (Genome Wide Location Analyses [GWLA], Chromatin Immuno-Precipitation (ChiP) and Expression analysis), and (b) to investigate the regulatory network profile of genes involved in the cell cycle machinery using the E2F 4 transcription factor as a marker. This enabled us to greatly enhance our understanding of diseases such as breast and melanoma cancer in humans by identifying their specific leader genes. The valuable information gained from the mapping of protein-protein interactions and regulatory networks focusing on defining biological processes in human may be a key to uncovered disease mechanisms and drugs discovery and development, by considering a drug's actions in the context of the cellular, cell cycle and DNA damage networks in which the drug targets function.