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Linda K. McLoon, Jonathan D. Wirtschafter; Direct Injection of Liposome-Encapsulated Doxorubicin Optimizes Chemomyectomy in Rabbit Eyelid. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2561-2567.
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purpose. Doxorubicin chemomyectomy presently represents the only permanent,
nonsurgical treatment for blepharospasm and hemifacial spasm. The major
deterrent to an otherwise extremely effective treatment protocol is the
development in patients of localized inflammation, discomfort, and skin
injury over the injection site. As a potential alternative therapy,
Doxil (Sequus, Menlo Park, CA), a liposome-encapsulated form of
doxorubicin that displays tissue-selective therapeutic effects compared
with free doxorubicin, was examined. These effects have been related to
its increased retention in tissues and its sustained release over time.
For the skin, Doxil is classified as an irritant rather than a
methods. Rabbits received direct injections of 1, 2, or 3 mg Doxil alone or in
sequence with other agents directly into the lower eyelids. The treated
eyelids were examined daily for signs of skin injury. One month after
the last injection, the rabbits were euthanatized, and their eyelids
were examined histologically for the effect of Doxil on the orbicularis
oculi muscle and the skin.
results. At equivalent milligram doses of free doxorubicin, Doxil spared the
skin from injury. Doxil was only approximately 60% as effective in
killing muscles as the same milligram dose of free doxorubicin.
However, either two injections of Doxil spaced 2 months apart or
preinjury of the lid with bupivacaine before a single dose of Doxil
treatment resulted in increased muscle loss compared with a single dose
of Doxil alone and was as effective as free doxorubicin. Higher doses
of Doxil did not increase the desired myotoxic effect; apparently, the
dose effect levels off at a maximum. Signs of skin injury were minimal;
there were small or no adverse skin changes at the maximum effective
conclusions. Injection of Doxil resulted in significant reduction of skin injury
compared with doxorubicin alone. Although single injections of Doxil
were myotoxic, multiple exposure of the eyelid to the
liposome-encapsulated form substantially improved myotoxicity while
sparing the skin. Repeated doses of the liposome-encapsulated form of
doxorubicin may be as clinically effective as free doxorubicin
injections and may produce fewer unwanted side
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