Vincristine-induced dermal toxicity is significantly reduced when the drug is given in liposomes |
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Authors: | N L Boman Victor A Tron Marcel B Bally Pieter R Cullis |
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Institution: | (1) The University of British Columbia, Biochemistry Department, 2146 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3, CA;(2) Vancouver General Hospital, Department of Pathology, Vancouver, British Columbia, Canada, CA;(3) British Columbia Cancer Agency, Division of Medical Oncology, 600 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 4E6, CA |
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Abstract: | A problem associated with the intravenous delivery of vincristine concerns drug extravasation at the site of injection or
infusion. This can result in extensive local soft-tissue damage. A new formulation of vincristine has recently been developed
based on encapsulation of the drug in liposomes. The liposomal drug is somewhat less toxic and substantially more efficacious
than free drug. The studies described here assessed, using a murine model of drug extravasation, whether vincristine encapsulation
in liposomes influences drug-induced dermal toxicity. It was shown that subcutaneous injection of vincristine in liposomes
does not result in the gross skin necrosis and ulceration observed following injection of free drug. Histological analysis
of the dermal tissue surrounding the injection site suggests that free drug induces a pronounced inflammatory reaction as
judged by the presence of infiltrating leukocytes. In contrast, the liposomal formulation of vincristine engenders a mild
prolonged inflammatory condition. These toxicological studies were correlated with an evaluation of drug retention at the
site of administration. It was shown using radiolabelled vincristine as a drug marker, that free vincristine is rapidly eliminated
from the injection site. In contrast, the level of drug at the site of injection was far greater when the drug was given in
liposomal form.
Received: 13 December 1994 / Accepted: 14 May 1995 |
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Keywords: | Vincristine Liposomes Dermal toxicity |
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