Purchase this article with an account.
Tsutomu Yasukawa, Hideya Kimura, Yasuhiko Tabata, Hideki Miyamoto, Yoshihito Honda, Yoshito Ikada, Yuichiro Ogura; Targeted Delivery of Anti–Angiogenic Agent TNP-470 Using Water-Soluble Polymer in the Treatment of Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2690-2696.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
purpose. The conjugation of drugs with water-soluble polymers such as poly(vinyl
alcohol) (PVA) tends to prolong the half-life of drugs and facilitate
the accumulation of drugs in tissues involving neovascularization. The
purpose of this study was to evaluate the effect of TNP-470–PVA
conjugate on the proliferation of endothelial cells in vitro and on
experimental choroidal neovascularization (CNV) in vivo.
methods. TNP-470 was conjugated in PVA by a dimethylaminopyridine-catalyzed
reaction. The effects of TNP-470–PVA and free TNP-470 on the
proliferation of human umbilical vein endothelial cells (HUVECs) and
bovine retinal pigment epithelial cells (BRPECs) were evaluated by the
tetrazolium-based colorimetric assay (XTT assay). Experimental CNV was
induced by subretinal injection of gelatin microspheres containing
basic fibroblast growth factor, into rabbits. Thirty rabbits were
intravenously treated either with TNP-470–PVA (n = 8),
free TNP-470 (n = 5), free PVA
(n = 5), or saline (n = 12)
daily for 3 days, 2 weeks after implantation of gelatin microspheres.
Fluorescein angiography was performed to detect the area with CNV, and
the evaluation was made by computerized measurement of digital images.
These eyes were also examined histologically. To observe the
accumulation of conjugate, 3 rabbits with CNV received rhodamine B
isothiocyanate–binding PVA (RITC–PVA), and the lesion was studied 24
hours later by fluorescein microscopy.
results. The TNP-470–PVA inhibited the growth of HUVECs, similar to that of
free TNP-470. The BRPECs were less sensitive to TNP-470–PVA than were
the HUVECs. TNP-470–PVA significantly inhibited the progression of CNV
in rabbits (P = 0.001). Histologic studies at 4
weeks after treatment demonstrated that the degree of vascular
formation and the number of vascular endothelial cells in the
subretinal membrane of the eyes treated with TNP-470–PVA were less
than those of the control eyes. RITC–PVA remained in the area with CNV
24 hours after administration.
conclusions. These results suggest that TNP-470–PVA inhibited the proliferation of
HUVECs more sensitively than that of BRPECs, and the targeted delivery
of TNP-470–PVA may have potential as a treatment modality for
This PDF is available to Subscribers Only