ANTIPROLIFERATIVE ACTIVITY OF A LIPOSOMAL DELIVERY SYSTEM OF MITOXANTRONE ON RABBIT SUBCONJUNCTIVAL FIBROBLASTS IN AN EX-VIVO MODEL

Wound healing is the main cause of the failure of filtering surgery in glaucoma. We developed a liposomal delivery system of mitoxantrone (M ITX), an anthracyclin derivative, to allow a single adjuvant administr ation and to lessen ocular side-effects of the drug. In order to evalu ate the antiproliferative activity of liposomal MITX, an ex vivo model consisting in the culture of subconjunctival tissue explants from rab bits pretreated with subconjunctival injections of free or liposomal M ITX was used. We found that both forms of MITX decreased the growth ra te as well as the explant proliferation surfaces 15 days or 1 month af ter a single administration of the drug in vivo. A morphometric analys is of the cells showed that the surface of the fibroblasts exposed to both forms of MITX was from 10 to 12 times as important as that of the control cells exposed to the empty liposomes and to the control buffe r, A radioautographic study showed that more than 95% of the fibroblas ts exposed to both forms of MITX were in the G1 phase of the cell cycl e, while the control cell population was equally distributed among the different phases of the cell cycle.