Isopropyl Unoprostone

Unoprostone induced a dose-dependent relaxation in rabbit ciliary arteries that were pre-contracted with high-K solution, 10 microM histamine or 10 microM PGF2alpha. Neither unoprostone metabolite M1 nor M2 had a relaxant effect on the precontracted vessels. Relaxation was unaffected by inhibition of adenylyl cyclase with SQ 22536, guanylyl cyclase with ODQ, or maxi-K channels with iberiotoxin. Pretreatment with unoprostone did not affect histamine-induced transient contractions in Ca2+-free solution. SKF96365, a general Ca2+ channel blocker, evoked relaxation similar to unoprostone with respect to amplitude and rate of onset. Unoprostone, but not its metabolites M1 and M2, relaxed pre-contracted rabbit ciliary artery.<>The mechanism of vascular smooth muscle relaxation by unoprostone differs from that of intraocular pressure reduction and does not depend on adenylyl cyclase, guanylyl cyclase, or maxi-K channels. Relaxation may be mediated by inhibition of Ca2+ entry, possibly through capacitative Ca2+ channels.

Fig. 1 Effect of unoprostone on the phasic and tonic components of ciliary artery contraction. (Yoshitomi T.; et al. 2004)

A sustained-release device for isopropyl unoprostone was fabricated using poly(ethyleneglycol) dimethacrylates as the polymer matrix. The device enabled controlled and prolonged release of the drug, potentially reducing dosing frequency and improving patient compliance in glaucoma management. The physicochemical properties of the polymer system were characterized, and biological evaluations confirmed the sustained release profile of unoprostone from the device. This implantable or insertable delivery system represents a novel approach for long-term intraocular pressure control, addressing the limitation of frequent topical administration associated with conventional eye drop formulations.

Fig. 2 Preparation of the sustained isopropyl unoprostone-release device. (Nagai N.; et al. 2017)