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Nanotechnology in Drug Delivery

H. Onyuksel, O. Koo, A. Krishnadas, V. Sethi and I. Rubinstein
University of Illinois at Chicago, US

Keywords:
drug delivery, nanotechnology, phospholipid molecules, sterically stabilized micells, SSM

Abstract:
Drugs with narrow therapeutic indexes create a major challenge for pharmaceutical scientists, during their developments. Application of nanotechnology for the delivery of such drugs can significantly overcome this problem. Works from our laboratory have demonstrated that nanosized (~ 15nm) self-assemblies of phospholipid molecules, sterically stabilized micelles (SSM) have numerous advantages as delivery systems to improve efficacy and reduce toxicity of drugs with narrow therapeutic indexes. Using various therapeutic agents, small insoluble molecules such as paclitaxel and camptothecin, or biologics such as vasoactive intestinal peptide (VIP) in these novel nanocarriers, we demonstrated on animal models that drug efficacy significantly increased while its toxicity decreased compared to free drug. The biodistibution and pharmacokinetic parameters of the drug in nanocarriers were also significantly improved compared to free drug. These results were attributed to passive and active targeting of the drug to the diseased sites due to the nano size of the carrier and leaky vasculature of the diseased tissues such as cancer and inflammation. Distribution of the micelle-associated drug to normal, non-target organs was reduced, decreasing drug toxicity. Most importantly, we have shown that the side effect elicited by VIP when delivered by this nanotechnology was totally eliminated because micelle associated peptide extravasated only in diseased tissues, not in normal tissues, to interact with VIP receptors only expressed at the extravascular compartment. In addition to their important role of carrying the drugs to target tissues, sterically stabilized micelles have several other advantages. Water-insoluble small drug molecules and peptides can be solubilized and/or stabilized in micelles’ hydrophobic or palisade region, they have an easy preparation technique, and they are composed of safe lipids that are already approved by FDA for human use. To conclude, our nanotechnology for drug delivery is particularly successful in increasing the therapeutic indexes of compounds applied to disease processes where leaky vasculature exists and allows preferential extravasation of the nanocarriers.

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