CHED 1627 |
| The biotechnology field has identified many new biomolecular drugs that act at intracellular sites such as the nucleus or the ribosomes, or interact with mRNA in the cytosol, or are processed via the MHC-1 pathway. Such drugs could be used to stimulate the cells within tissue-engineered scaffolds to differentiate into a desired phenotype and/or to proliferate. They could also act to control expression of inflammatory mediators such as TNF± from the inflammatory cells that respond to the implanted scaffold. However, the effective intracellular delivery of these bioactive macromolecules remains a significant challenge. Key intracellular drugs include nucleic acid drugs such as DNA, RNA, antisense oligonucleotides (AS-ODNs) and siRNA, and also protein and peptide drugs such as vaccines and immunotoxins. Passive or receptor-mediated endocytosis of drug formulations results in localization within the endosome, where the predominant trafficking fate is fusion with lysosomes and subsequent enzymatic degradation of the biomolecular drug. A variety of viruses and toxins have evolved pH-dependent fusogenic proteins to overcome this barrier by enhancing endosomal escape to the cytoplasm at the acidic pH of the endosome. Inspired by the principle behind this biological strategy, we have designed a new family of biomimetic, pH-responsive polymeric carriers that enhance delivery of fragile drugs to the cytosol from the endosomes. |
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Exploring and Exploiting Nature with Biomimetics
1:30 PM-4:45 PM, Tuesday, March 27, 2007 McCormick Place North -- Room N230A, Level 2, Oral
Division of Chemical Education |