Lipid-based nanosystems and complexes in experimental and clinical therapeutics
Moghimi, S.M. and Agrawal, A. (2005) Lipid-based nanosystems and complexes in experimental and clinical therapeutics Current Drug Delivery, 2 (4). pp. 295-296. ISSN 1567-2018
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Official URL: http://dx.doi.org/10.2174/156720105774370276
An intriguing spectrum of novel nanoparticulate systems and complex nanostructures, some with remarkable diagnostic and biomimetic properties and others suitable for site-specific drug delivery and targeting are in existence today. Examples include quantum dots, capable of labelling biological systems for detection by optical or electrical means, tris-malonic acid derivatives of the fullerene C60, which exhibit superoxide dismutase mimetic properties, and porous titanium oxide and silicon nanoparticulate systems with sustained drug release properties. The ability to create these assemblies as well as other unusual nanostructures such as bundles, tubes, and sheets holds promise for new and powerful diagnostic and drug delivery systems, which will surely change the foundations of disease treatment and diagnosis. These technological innovations and nanoscience approaches to particle design are the focus of the US National Institute of Health's Nanomedicine Roadmap Initiative and the National Cancer Institute's Alliance for Nanotechnology in Cancer and several new European Commission-funded initiatives. Indeed, February 2004 saw the birth of Nano2Life, Europe's first Network of Excellence in nanobiotechnology, and in February 2005, the European Science Foundation launched its Scientific Forward Look on Nanomedicine Initiative, with strong emphasis on engineering of smart nanoparticle-based medicines and nanodevices. Although within the remit of the above mentioned nanoscience initiatives, lipid-based nanosystems such as nanoemulsions, lipid-core micelles, small unilamellar vesicles and variations thereof, have long been in existence and some have long been improving patient's lives. Indeed, lipid-based nanoformulations are among the most attractive candidates for improving drug solubility and for site-specific targeting following parenteral administration. This Theme Issue of Current Drug Delivery features contributions focusing on selected molecularbased strategies and nanoscience approaches to design, development, and site-specific targeting of a wide range of lipid-based nanocarriers and complex systems currently at preclinical and clinical stages. Specifically, great strides are being made with such complexes and nanosystems in combating the growth and spread of cancerous tissues (e.g., through exploitation of angiogenic tumour vasculature, combination chemotherapy, and endogenous triggered activation and release of encapsulated lipid pro-drugs), treatment of macrophage infections (through exploitation of macrophage clearance mechanisms), gene transfer (by breaching the endo-lysosomal barrier with cationic lipid vectors) and stimulation of immune responses to antigens (with the aid of vesicular systems and lipid-complexes with self-adjuvanting properties), and are discussed in the first thirteen articles in this Theme Issue. Although, lipidbased nanocarriers may overcome solubility or stability issues for the drug and minimize drug-induced side effects through favourable pharmacokinetic profiles and site-specific targeting, there are significant toxicity issues with carriers themselves that need to be addressed. Selected toxicity issues are dealt with in the last two articles. The first contribution discusses toxicogenomics of the delivery system and the impact of the microarray technology; in assessing cellular toxicity, while in the final article, the reader's attention is drawn towards pseudoallergic reactions, which are believed to be secondary to complement activation. Here, endogenous lipid-based delivery vehicles (lipoproteins) seem to play a complex modulatory role in complement-mediated pseudoallergic responses to nanomedicines. We believe that this Issue has provided a broad sample of the state of the art. We are indebted to all contributors for their attempt to communicate and discuss the most promising ideas, approaches, applications and developments of the most advanced lipid-based nanomedicines.
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