Historical

In the late 1960s and early 1970s Professor Peter Speiser at the ETH (Swiss Federal Institute of Technology) in Zürich realized Paul Ehrlich's idea and developed the first nanoparticles for drug delivery purposes [12-14]. These first nanoparticles were produced by emulsion polymerization of acrylamide crosslinked with N,N'-methylenebisacrylamide in hexane.

Independently, Zolle et al. [15] and Scheffel et al. [16] used another process, denaturation of albumin dissolved in water and emulsified in hot cottonseed oil, to produce nanoparticles. 99mTcO- was bound to the nanoparticles, and these particles were used for radioimaging of the lungs after intravenous injection.

Later the albumin nanoparticles were also used for drug delivery. Kramer [17] incorporated the anticancer drug mer-captopurine into these particles using the method of heat denaturation (Section 4.5).

The first successful drug targeting with nanoparticles was then performed by Widder and Senyei [18-22] by

Copyright © 2004 by American Scientific Publishers All rights of reproduction in any form reserved.

Encyclopedia of Nanoscience and Nanotechnology Edited by H. S. Nalwa Volume 7: Pages (161-180)

Figure 1. Schematic presentation of nanoparticles. (a) Monolythic nanoparticles with a continuous matrix. (b) Nanocapsules with a shelltype wall.

incorporation of magnetite particles into similar albumin nanoparticles and the employment of a magnetic field. These authors substituted mercaptopurine by the more efficient anticancer drug doxorubicin. Couvreur et al. [23-25] later could demonstrate that nonmagnetic nanoparticles also could accumulate in certain solid tumors and thus were able to substantially enhance the therapeutic efficacy of anticancer drugs such as doxorubicin or dactinomycin. This accumulation of the nanoparticles in these tumors probably was due to the enhanced permeability and retention effect (EPR effect) first described by Maeda and Matsumura [26] (see Section 6.1.1).

The latest important steps in the improvement of drug targeting with nanoparticles were the development of long circulating nanoparticles by the covalent linkage of polyethylene glycol (PEG) chains to poly(lactic-co-glycolic acid) (PLGA) [27] or to poly(alkyl cyanoacrylate) nanoparticles [28, 29] and the targeting of drugs to the brain across the blood-brain barrier [30].

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