Abstract
The delivery of some classes of drugs is challenging. Solubility, absorption, distribution, and duration of action may all be altered by combination with vehicle molecules. It has already been discovered that polyethylene glycol – which is used as a stabiliser in peptide drug formulations – has biological activity in its own right, including potential neuroprotective properties. In this article we review the evidence for confounding activity for four distinct compounds that have been used as solvents and/or carrier molecules for the delivery of lipophilic drugs under investigation for potential neuroprotective properties. We discuss the evidence that cyclodextrins, ethanol, dimethyl sulphoxide, and a castor oil derivative - Cremophor™ EL – have all been found to have mild to moderate neuroprotective effects. We argue that this has probably reduced the statistical power and increased the Type II error rates of neuroprotection experiments that have employed these vehicles, and suggest experimental design considerations to help correct the problem. However, we also note that the properties of these compounds may represent an opportunity for drug development, particularly for the newer compounds that have been subject to only limited experimental investigation.
Keywords: Carrier, Cyclodextrin, DMSO, Ethanol, Cremophor, Lipophilic, Neuroprotection, Vehicle.
Current Neurovascular Research
Title:Vehicles for Lipophilic Drugs: Implications for Experimental Design, Neuroprotection, and Drug Discovery
Volume: 10 Issue: 4
Author(s): Jack Rivers-Auty and John C. Ashton
Affiliation:
Keywords: Carrier, Cyclodextrin, DMSO, Ethanol, Cremophor, Lipophilic, Neuroprotection, Vehicle.
Abstract: The delivery of some classes of drugs is challenging. Solubility, absorption, distribution, and duration of action may all be altered by combination with vehicle molecules. It has already been discovered that polyethylene glycol – which is used as a stabiliser in peptide drug formulations – has biological activity in its own right, including potential neuroprotective properties. In this article we review the evidence for confounding activity for four distinct compounds that have been used as solvents and/or carrier molecules for the delivery of lipophilic drugs under investigation for potential neuroprotective properties. We discuss the evidence that cyclodextrins, ethanol, dimethyl sulphoxide, and a castor oil derivative - Cremophor™ EL – have all been found to have mild to moderate neuroprotective effects. We argue that this has probably reduced the statistical power and increased the Type II error rates of neuroprotection experiments that have employed these vehicles, and suggest experimental design considerations to help correct the problem. However, we also note that the properties of these compounds may represent an opportunity for drug development, particularly for the newer compounds that have been subject to only limited experimental investigation.
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Cite this article as:
Rivers-Auty Jack and Ashton C. John, Vehicles for Lipophilic Drugs: Implications for Experimental Design, Neuroprotection, and Drug Discovery, Current Neurovascular Research 2013; 10 (4) . https://dx.doi.org/10.2174/15672026113109990021
DOI https://dx.doi.org/10.2174/15672026113109990021 |
Print ISSN 1567-2026 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5739 |
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