F. Maignen et al., ANTIPROLIFERATIVE ACTIVITY OF A LIPOSOMAL DELIVERY SYSTEM OF MITOXANTRONE ON RABBIT SUBCONJUNCTIVAL FIBROBLASTS IN AN EX-VIVO MODEL, Journal of ocular pharmacology and therapeutics, 12(3), 1996, pp. 289-298
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.