The Effect of Liposome-Encapsulation and Dimethyl Sulfoxide (DMSO) on the Protection of Eyelid Skin in Chemical Myectomy Using Doxorubicin Injection

ABSTRACT

PURPOSE: Doxorubicin has an effect of permanently removing muscle after direct injection into the eyelid for treatment of blepharospasm. However, the major dilemma of this attractive treatment is the necrosis of skin overlying the orbicularis oculi muscle. This study was to evaluate whether liposome-encapsulated doxorubicin (Doxil R ) and dimethyl sulfoxide (DMSO) could decrease the incidence and severity of the skin necrosis. METHODS: 0.5, 1, 2 mg of doxorubicin, Doxil and a combination of doxorubicin with DMSO were injected into eyelids of rabbits, respectively. Animals were examined daily on onset, duration, and the size of skin necrosis after each injection. For the evaluation of functional change of muscle after doxorubicin injection, EMG study was conducted and the eyelids were examined histologically and the amount of muscle loss were measured by means of a NIH image analysis program. Electronmicroscopic morphology was also assessed. RESULTS: Doxil decreased the duration and size of skin necrosis, incidence of ectropion, and delayed the onset of skin necrosis markedly. Doxil was more effective in the protection of skin from necrosis than a combination of doxorubicin and DMSO. Compared with free doxorubicin, doxil had 79.2% of myectomy effect. Although doxil was less effective in myectomy than free doxorubicin, excellent myectomy effect was functionally proved on EMG study. A combination of DMSO and doxorubicin had 84.1% of myectomy effect compared with doxorubicin alone but the difference was not significant. In electronmicroscopic study, loss of Z-disc and I-band and segmental disorganization of myofibrills were observed in all three groups. CONCLUSIONS: Both Doxil and a combination of doxorubicin and DMSO improved safety of doxorubicin chemomyectomy by prevention of skin necrosis. Doxil 1.0 mg was most effective in protection of skin from necrosis.