Doxil-induced chemomyectomy: effectiveness for permanent removal of orbicularis oculi muscle in monkey eyelid.
OBJECTIVE
To test the safety and effectiveness of Doxil chemomyectomy in monkey eyelids using treatment schedules and doses similar to those proposed for the human blepharospasm patients in Phase I and II trials.


METHODS
Bupivacaine/hyaluronidase and Doxil were injected sequentially into the eyelids of five Cynomolgus monkeys. Eyelids received 1, 2, or 3 sets of injections. The monkeys were euthanatized at a minimum of 2 months and a maximum of 12 months after the final treatment. The eyelids were prepared for histologic examination, and muscle fiber loss was quantified.


RESULTS
All Doxil injections resulted in a significant loss of myofibers. No bruising, ulceration, or other skin injuries occurred, even after a third injection regimen within a single treated eyelid. Two-day preinjury with a bupivacaine/hyaluronidase mixture had a significant adjuvant effect.


CONCLUSIONS
Doxil chemomyectomy is an effective protocol to permanently remove muscle from injected eyelids in nonhuman primates. Serial injections over the course of several months using the preinjury protocol combined with Doxil treatment significantly increased Doxil's myotoxic effects. Additionally, the injection of the liposome-encapsulated form of doxorubicin did not result in skin injury or ulceration. Species differences demonstrated the importance of testing these drugs in nonhuman primates. Thus, repeated doses of Doxil may prove to be as clinically effective as free doxorubicin injections in reducing muscle spasms in blepharospasm patients but with increased safety to the skin and tissue around the injection site.
McLoon
L K
LK
Department of Ophthalmology, University of Minnesota, Room 374 Lions Research Building, 2001 6th Street SE, Minneapolis, MN 55455, USA. mcloo001@tc.umn.edu
Wirtschafter
J D
JD
D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D005143:Eyelids / Q000187:drug effects* / Q000294:innervation / Q000473:pathology; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage / Q000494:pharmacology; D007267:Injections; D008081:Liposomes; D008252:Macaca fascicularis; D009121:Muscle Denervation / Q000379:methods*; D009801:Oculomotor Muscles / Q000187:drug effects* / Q000294:innervation / Q000473:pathology; D012449:Safety
D008081:Liposomes; D004317:Doxorubicin; D006821:Hyaluronoglucosaminidase; D002045:Bupivacaine