Author: Szebeni, Janos

Source: Current Drug Delivery, Volume 2, Number 4, October 2005 , pp. 443-449(7)

Publisher: Bentham Science Publishers

Abstract:

Self-assembling amphiphilic lipids or polymers have been successfully used in pharmacotherapy as drug solvents or carriers, improving the bioavailability of water-insoluble drugs. This review focuses on an unusual hypersensitivity reaction (HSR) caused by a micellar (Cremophor EL, CrEL) and a monomeric block copolymer (poloxamer 188) representative of these systems. The HSRs, also referred to as anaphylactoid or pseudoallergic, are thought to arise as a consequence of complement (C) activation in blood. However, considering that C activation involves the deposition of multiple C and other (immune) proteins on the activator surface, the mechanism by which small, 8-25 nm CrEL micelles or individual poloxamer 188 molecules activate C is not straightforward. Observations on enlarged lipoproteins and de novo formation of abnormally large lipoprotein-like structures in plasma exposed to CrEL or poloxamer 188 raise the possibility that lipoprotein transformation might play a crucial role in C activation by these amphiphilic emulsifiers. Lipoproteins, furthermore, can also provide a negative feedback control on C activation, as suggested by the inhibition of poloxamer 188-induced C activation in the presence of excess exogenous lipoproteins, and the attenuation of liposome-induced and C activation-related hypotension in pigs by precoating the vesicles with lipoproteins. Thus, lipoproteins may be essential in the induction, and they may also play a complex modulatory role in C activation-related pseudoallergy caused amphiphilic drug solvents and carriers.

Keywords: cremophor el; taxol; poloxamer; micelles; anaphylatoxins; anaphylactoid reaction; cancer chemotherapy; drug targeting; lipoproteins

Document Type: Review article

DOI: http://dx.doi.org/10.2174/156720105774370212

Affiliations: 1: Department of Vaccine Production and Delivery, Division of Retrovirology, Walter Reed Army Institute of Research and Henry Jackson Foundation for Military Medical Research, Silver Spring, MD, USA and 1Semmelweis University, Nephrology Research Gr

Publication date: 2005-10-01

More about this publication?

• The aim of Current Drug Delivery is to publish peer-reviewed articles, short communications, short and in-depth reviews in the rapidly developing field of drug delivery. Modern drug research aims to build in delivery properties of a drug at the design phase, however in many cases this ideal cannot be met and the development of delivery systems becomes as important as the development as the drugs themselves.
  
  The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance.
  
  The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.

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