Graefe's Archive
Graefe's Arch Clin Exp Ophthalmol (1990)228:533-537
for Clinical and Experimental
Ophthalmology © Springer-Verlag1990
Evaluation of polyvinyl alcohol hydrogel as a soft contact lens material* Mihori Kita 1, Yuichiro Ogura 1, Yoshihito Honda 1, Suong-Hyu Hyon 2, Won-II Cha 2, and Yoshito Ikada 2 1 Department of Ophthalmology, Faculty of Medicine, Kyoto University, Sakyo-ku Kyoto, 606 Japan z Research Center for Medical Polymers and Biomaterials, Kyoto University, Kyoto, Japan Received August 15, 1989 / Accepted May 4, 1990
Abstract. We prepared a transparent polyvinyl alcohol (PVA) hydrogel from a PVA solution in a mixed solvent consisting of water and a water-miscible organic solvent by cooling. The physical properties of the hydrogel were evaluated in various mixed solvents and c o m p a r e d with those of commercially available soft contact lens materials, such as polyhydroxyethyl methacrylate ( P H E M A ) and copolymers of methylmethycrylate ( M M A ) and Nvinyl pyrrolidone (N-VP). The PVA hydrogel showed higher tensile strength and elongation before breaking than did the other materials. Also, the PVA hydrogel was comparable in its high water content and its oxygen permeability with the M M A / V P copolymers. The protein adsorption of the PVA hydrogel was much lower than that of the other materials. Soft contact lenses of PVA hydrogel were applied to rabbit eyes for 12 weeks. The effects of the lenses on the cornea were studied by biomicroscopy, ultrasonic pachymetry, and histopathologic examination. No abnormal findings were noted, suggesting that the PVA hydrogel m a y be promising as a new material for use in soft contact lenses.
Thinner SCLs and those with a high water content have been developed to increase oxygen permeability, which should extend wearing time. One of the problems encountered with such lenses, however, is the formation of proteinaceous deposits on the lens due to tears, which are liable to be produced precisely because o f the thinness of such lenses. Also, the higher water content of the c o m m o n hydrogel induces less strength in stretch and elongation. The production of improved materials for SCLs would therefore be quite desirable. We developed a new method for the preparation of polyvinyl alcohol (PVA) hydrogel. This PVA hydrogel has not only a high water content and good transparency but also high tensile strength and elongation. In this study, we evaluated the physical properties and biocompatibility of PVA hydrogel contact lenses that were applied to rabbit eyes.
Materials and methods A polyvinyl alcohol (average degree of polymerization, 1,700 viscosity; degree of saponification, 99.5 mol%) was obtained from Unichika Company (Osaka, Japan). The repeating unit of PVA has a hydroxyl group as shown below:
Introduction Soft contact lenses (SCL) have achieved widespread use in the correction of refractive error owing to wearer comfort and their relatively high oxygen permeability as c o m p a r e d with hard contact lenses m a d e of polymethylmethacrylate. Usually SCLs are made of polyhydroxyethyl methacrylate ( P H E M A ) , but this material is not wholly satisfactory because of its rather low oxygen permeability, which m a y induce hypoxia o f the cornea. * The developments discussed in this paper were presented in part at the Annual Meeting of the Association for Research in Vision and Ophthalmology, Sarasota, May 1988 Offprint requests to: Y. Ogura
( -- CH2CH - ) n
I
OH Glycerin (GC), ethylene glycol (EG), and dimethylsulfoxide (DMSO) were used as organic solvents. The composition of solvents was described by weight. A PVA hydrogel was prepared from a PVA solution in solvents consisting of water and a watermiscible organic solvent. Cooling the PVA solution to below room temperature enabled a gel to form following the crystallization of the PVA molecules. An exchange of organic solvent in the gel with water produced a PVA hydrogel. The tensile strength of the PVA hydrogel and the elongation of the material at its breaking point were measured with an Autograph S-100 (Shimazu Kyoto, Japan) at 25°C and a relative humidity of 65% under a tensile speed of 100 mm/min and were taken as the mean values of five measurements. The samples were stamped out with a dumbbell tert piece in accordance with Japan
534 Industrial Standard (JIS) criteria. Light transmittance at 550 nm was measured with a spectrophotometer 200-20 (Hitachi-shi, Japan) for a hydrogel film of 0.2-mm thickness immersed in water at 25° C. Oxygen permeability of the hydrogel film was measured at 35° C with a conventional gas-permeation apparatus used for polymer films (Kaken) [7]. Protein adsorption was conducted at 37°C using immunoglobulin G (IgG), bovine serum albumin (BSA), and lysozyme. Labeling of the protein with iodine-125 was performed by the chloramine-T method [1]. To a PVA we added the mixed solvents of water and DMSO so as to obtain PVA concentrations of 10%. PVA solutions were obtained after the mixture was heated for 2 h at 110° C. Following cooling of the PVA solutions to a temperature range of 50-60 ° C, they were poured into a mold. One surface of the mold was approximately spherical and convex, whereas the other had a spherical interface and was concave. The PVA solution in the mold was allowed to stand for 1 h in a freezer kept at - 2 0 ° C. The resulting PVA gel was taken out of the mold and the organic solvents in the gel were exchanged with water by immersion of the gel in enough water to give a PVA soft contact lens. The diameter, base curve, and central thickness of the lens were designed to be 14, 8, and 0.17 mm, respectively. For evaluation of the physical properties of the PVA lens, commercial lenses made of copolymers of methylmethacrylate (MMA), N-vinyl pyrrolidone (N-VP), and polyhydroxyethyl methacrylate (PHEMA) were compared in terms of water content, tensile strength, elongation before breaking, light transmittance, oxygen permeability, and protein adsorption. At this time, the thickness of the lenses was uniformly set at 0.2 mm. The PVA hydrogel contact lenses were applied to 19 albino rabbit eyes for 12 weeks. Slit-lamp biomicroscopic examination was performed at I and 3 days and at 1, 3, 6, 9, and 12 weeks after application. At each examination, light microscopy was carried out following enucleation of the eyes, which were then fixed in 20% formaldehyde and stained with hematoxylin and eosin. At 6 and 9 weeks after application of the lenses, enucleated eyes were fixed in 2.5 % glutaraldehyde and then processed for scanning electron microscopy using routine techniques. The central corneal thickness was evaluated using an ultrasonic pachymeter (DGH 2000) in vivo. The measurement was obtained before insertion of the contact lens and 2, 4, and 6 weeks thereafter. Five readings were taken of each eye, and the mean values were recorded and compared with those from control rabbits.
20 4E
,
1000
15
750
_m o
x=
500
2
-~
o
250
5~
0 0 20 40 60 80 1 O0 Concentration of GC in water (w/w%)
Fig. 1. Measurements of the tensile strength (o) and elongation (o) of PVA hydrogels at different concentrations of glycerin (GC) in water
1000
10.0
o
7.5
750
== =
5.0
500
=~
2.5
250
0
I
I
I
rn
6 =
I
0 20 40 60 80 1 O0 Concentration of EG in water (w/w%)
Fig. 2. Measurements of the tensile strength (o) and elongation (o) of PVA hydrogels at different concentrations of ethylene glycol (EG) in water
20
000
g15
750 m
o
Results T h e r e l a t i o n s h i p b e t w e e n the tensile s t r e n g t h a n d the e l o n g a t i o n was c o m p a r e d for c o n c e n t r a t i o n s o f glycerin, ethylene glycol, a n d D M S O in P V A h y d r o g e l s crystallized at - 2 0 ° C for 24 h (Figs. 1-3). In all o r g a n i c solvents, b o t h the tensile s t r e n g t h a n d the e l o n g a t i o n dep e n d e d on the m i x t u r e o f the solvents. T h e P V A h y d r o gel p r e p a r e d f r o m m i x e d solvents o f w a t e r a n d D M S O at a r a t i o o f 2 0 : 8 0 s h o w e d the highest tensile s t r e n g t h a n d the highest e l o n g a t i o n b e f o r e b r e a k i n g . U s i n g this m i x e d solvent, the r e l a t i o n s h i p b e t w e e n the tensile s t r e n g t h a n d e l o n g a t i o n o f the P V A h y d r o g e l s a t v a r i o u s P V A c o n c e n t r a t i o n s was n o t e d (Fig. 4). T h e tensile strength markedly increased with higher concentrations o f P V A . T h e e l o n g a t i o n b e f o r e b r e a k i n g i n c r e a s e d at a PVA concentration of 20% but decreased at a concent r a t i o n o f 2 5 % P V A . T h e r e l a t i o n s h i p b e t w e e n the light t r a n s m i t t a n c e o f P V A h y d r o g e l s a n d the c o n c e n t r a t i o n o f D M S O is s h o w n in Fig. 5. T h e t r a n s m i t t a n c e increased with increasing concentrations of DMSO, reaching the m a x i m a l level at a D M S O c o n c e n t r a t i o n o f 8 0 % .
x=
¢o
10
~500
5
250
0
I
I
/
-~. o
I
0 20 40 60 80 O0 Concentration of DMSO in water (w/w%)
Fig. 3. Measurements of the tensile strength (o) and elongation (o) of PVA hydrogels at different concentrations of dimethylsulfoxide (DMSO) in water
T h e surfaces o f the h y d r o g e l s o b t a i n e d f r o m w a t e r a n d D M S O - m i x e d s o l u t i o n s o f P V A were o b s e r v e d w i t h s c a n n i n g e l e c t r o n m i c r o s c o p y (Fig. 6). T h e h y d r o g e l s h a d a p o r o u s structure, the p o r e d i a m e t e r o f w h i c h became smaller with increasing concentrations of DMSO. N o clearly p o r o u s s t r u c t u r e was o b s e r v e d at c o n c e n t r a tions o f 6 0 % a n d 8 0 % . T h e P V A h y d r o g e l s t h a t were p r e p a r e d f r o m a 2 0 % P V A s o l u t i o n in a m i x e d s o l v e n t c o n s i s t i n g o f 2 0 % w a t e r
535 50
1000
40
800
100
r'n
30
600
¢o 5 ¸
20
E co
50
c
400 v
200
lO 0
,
0
,
lO
,
,
,
20
25 _J
0
3o
PVA concentration (%)
0
I
0
I
I
I
20
40 60 80 O0 Concentration of DMSO in water (w/w%)
Fig. 4. Relationship between the tensile strength (©) and elongation (e) of PVA hydrogels and their concentration of PVA (water: DMSO ratio, 20 : 80)
Fig. 5. Measurements of the light transmittance of PVA hydrogels at different concentrations of dimethylsulfoxide (DMSO)
and 80% DMSO showed the best physical properties observed in this experiment. Subsequently, PVA hydrogel contact lenses were made of this material, and its physical properties and protein adsorption were compared with those of commercial lenses. The tensile strength of the PVA hydrogel was 5 and 2.5 times that of the PHEMA hydrogel and copolymers of MMA and N-VP, respectively. The elongation of the PVA hydrogel
at its breaking point was about 3 times that of the other materials. The light transmittance did not differ among the three materials. The PVA hydrogel showed almost the same oxygen permeability as the copolymers of MMA and N-VP, the value of which was about 4.5 times that of the PHEMA hydrogel (Table 1). Table 2 presents the results of protein adsorption for the three hydrogels. The PVA hydrogel picked up considerably
Fig. 6A-F. Scanning electron micrographs of PVA hydrogels obtained from water and DMSO-mixed solutions of PVA. The ratios of water:DMSO are A 100:0; B 80:20; C 60:40; D 40:60; E 20:80; and F 0:100. Bars= 5 ~tm
536 Table 1. Physical properties of hydrogels
PVA
PHEMA
MMA/VP
78 47 500 99-100 44
38 10 160 99-100 10
78 19 160 99-100 46
Water content (%) Tensile strength (kg/cm z) Elongation (%) Light transmittance (%)a 02 permeability u
Discussion
a 550 nm, 0.2 mm thick in water b 10 11 cm 3 (STP) cm2/cm 3 s mm Hg (35 ° C)
Table 2. Protein adsorption rates of hydrogels
PVA PHEMA MMA/VP
ings in the epithelium, stroma, or endothelium. Also noted by scanning electron microscopy were an epithelium of normal shape and villous structure and an unaltered endothelium (Fig. 7). No difference in corneal thickness was noted between eyes wearing the PVA hydrogel contact lens and control eyes (Table 3).
Water content (%)
IgG (gg/cm z)
BSA (gg/cm 2)
Lysozyme (gg/cm 2)
78 40 78
0.074 0.271 0.889
0.005 0.037 0.169
0.195 0.230 4.991
IgG, immunoglobulin G; BSA, bovine serum albumin
Table 3. Results of corneal pachymetry after application of PVA
hydrogel contact lens to rabbit eyes Before
2 weeks
4 weeks
6 weeks
PVA contact lens-wearing eyes a
376+_16 (6)
374_+13 (4)
373+_17 (7)
376-+21 (4)
Controls (n=4)
373_+/1
373_+10
a Data represent the mean _+ SD (gm) values; figures in parentheses indicate the number of eyes examined
less protein than did the other hydrogels, regardless of the kinds of protein used. Slit-lamp biomicroscopic examination revealed no abnormal findings such as conjunctival hyperemia, corneal edema, corneal neovascularization, or lens pollution during the experimental period. Histologic study of the cornea by light microscopy showed no abnormal find-
The PVA hydrogel has been used as the material for a dialytic membrane; because of its high water content and strength, it has been considered for potential use in artificial vessels, nonadhesive membrane for intestines, artificial vitreous, and scleral buckles [2-5]. A PVA hydrogel was recently reported to be optimal for creation of a perforating keratoprosthesis [6]. PVA hydrogels, which are bridged with glyoxal or borate, have previously been proposed for use as soft contact lens (SCL) materials. However, with these uses came concerns about residual material and degenerative products that might act as stimulants on the cornea. In this study, we successfully prepared transparent PVA hydrogel from a PVA solution in a mixed solvent. The organic solvent depressed the freezing point, which prevented a change in the volume of crystallization due to freezing. The PVA hydrogel had no porous structure and was therefore transparent and less likely to adsorb protein. The PVA hydrogel prepared from an 80:20 mixture of DMSO and water showed the most advantageous physical properties among the various mixtures. It was about 4 times stronger then P H E M A hydrogel, which is commonly used for the production of daily-wear lenses, and about 2.5 times stronger than the copolymers of M M A and N-VP, whose water content is comparable with that of PVA hydrogel. This finding might indicate that the material is difficult to break and easy to treat. Although PVA hydrogel has twice the water content of the copolymers of M M A and N-VP, it showed remarkably less adsorption than the other materials. This feature might be one of the most important aspects of the PVA hydrogel, as lens pollution presents a severe
Fig. 7A-C. Scanning electron micrographs of the cornea taken at 9 weeks: A epithelium; B endothelium; C control. Bars: A, 1 gin; B, C, 5 gm
537 problem, especially in the use o f extended-wear lenses and b a n d a g e c o n t a c t lenses. The P V A itself is a harmless substance. The translucent P V A h y d r o g e l reportedly p r o d u c e d no a b n o r m a l reaction with the tissue w h e n it was implanted in in vivo situations [4, 5]. In the present study, the transparent P V A hydrogel induced no m o r b i d findings during the entire period o f observation. O u r results suggest that P V A hydrogel offers excellent mechanical properties a n d biocompatibility and that it m a y be promising as a new S C L material. A d d i t i o n a l studies should c o n f i r m its worth.
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2. Hara Y, Hara T, Hatanaka O, Hikari H, Ichiba S, Kamiya S, Nakao S, Saishin M (1984) The effect of PVA (polyvinyl alcohol) hydrogel on the retinas of albino rabbits. Folia Ophthaltool Jpn 35:1340-1344 3. Kim SY, Honda Y (1985) A new polyvinyl alcohol hydrogel as a scleral buckling material. Am J Ophthalmol 100:328-330 4. Tamura T, Nakamura T, Okada K, Mizuno H, Shimizu Y, Ito M, Teramatsu T, Nanbu M (1984) New hydrogel from polyvinyl alcohol and its fundamental study for medical application: histological evaluation. Jpn J Artif Organs 13:1197-1200 5. Tamura K, Nakamura T, Ike O, Mizuno H, Okada K, Hitomi S, Shimizu Y, Nanbu M (1986) New hydrogel from PVA and its fundamental study for medical application : change of properties after implantation and application as non-adhesive membrane for intestines. Jpn J Artif Organs 15:260-263 6. Trinkaus-Randall V, Capecchi J, Newton A, Vadasz A, Leibowittz H, Franzblau C (1988) Development of a biopolymeric keratoprosthetic material. Invest Ophthalmol Vis Sci 29 : 393-400 7. Yajima Y, Yoshida H, Ito N, Kanai A, Momose T, Hosaka S, Otsuka H (1980) Experiences of extended wear of soft contact lenses with a water content of 80% made by a static molding method. J Jpn Contact Lens Soc 22:132-139