Technical note
Polymeric hydrogels for soft contact lenses J. Singh, K. Agrawal, A. R. Ray, J. P. Singhal, and H. Singh* Centre for Biomedical Engineering, Indian Institute of Technology Delhi, H a m Khas, New Delki-110016. India V. K. Dada and Manoj R. Mehta Contact Lens Division, Dr. Rajendra Praskad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delki-110029, India
INTRODUCTION
The use of hydrogels for surgical implants and contact lenses was first proposed by Wichterle and Lim.’ HydrogeIs are particularly attractive for corneal lenses’ because they possess excellent optical qualities, and because they are soft and can be molded to conform to the corneal curvatures. In addition, their permeability to water and to lowmolecular-weight soluble substances can be regulated by modifying the molecular structure of the gel. Hydrogels of poly (2-hydroxyethyl methacrylate) (PHEMA)3and poly (glyceryl methacrylate) (PGMA)4 are well tolerated by the eye tissues.s N-Vinyl pyrrolidone (NVP) is the most effective comonomer used to increase the ability of HEMA hydrogels to take up more water. Several manufacturers of contact lenses use random copolymers of HEMA and NVP. Homopolymers of N-vinyl pyrrolidone have poor mechanical properties; therefore, hydrophobic monomers are used to improve mechanical properties. Contact lens materials based on copolymers of N VP, HEMA, and methacrylates have been reported by various No report is available on the preparation of NVP and hydroxypropyl methacrylate (HPMA) copolymers for contact and intraocular lenses. In the present study attempts have been made to prepare copolymers based on Nvinyl pyrrolidone, methyl methacrylate, and hydroxypropyl methacrylate for soft contact and intraocular lenses.
MATERIALS A N D METHODS
N-vinyl pyrrolidone (NVP), methyl methacrylate (MMA), and hydroxypropyl methacrylate were obtained from Fluka A.G. (Germany) and used after distillation under vacuum.” Ethylene glycol dimethacrylate (EDMA) was also obtained from Fluka AG. (Germany) and was used without any purification.
* To whom all correspondence should be addressed. Journal of Biomedical Materials Research, Vol. 26, 1253-1257 (1992) ccc 0021-9304/92/091253-05$4.00 0 1992 John Wiley & Sons, Inc.
SINGH ET AL.
1254
Methods
Copolymerization Copolymerization was carried out using a 6"Co-gamma radiation technique. Monomers with 1% EDMA were taken in ampules of 11.5 mm diameter. Monomers were degassed and ampules were sealed under vacuum. Ampules were exposed to yradiation for a total dose of 0.55 Mrad at a dose rate of 56 rads/s. After polymerization, ampules were broken and cross-linked copolymers in the form of transparent rods were obtained. Residual monomer was extracted by keeping it in boiling water for 36 h. Feeding ratios of various monomers are given in Table I. Hydration was determined by weight difference after equilibrium was reached.
Hydration
=
(Wet wt) - (dry wt) x 100 Wet wt
Specific gravity of the hydrogel was determined by dividing the weight of the specimen in air by its weight in water. Hardness was measured with a Shore D durometer according to ASTM standard D2240-75. The refractive index of hydrogels was measured with the help of an Abbe's refractometer. Transparency was measured on a UVvisible spectrophotometer (Hitachi Model 260) for visible light 0.35-0.8 pm. Wettability of hydrogels was measured by the contact angle method. The contact angle of a water drop on the surface was determined by a Goniometer Model 100-00-230 (Rame-Hart, Inc., Mountain Lakes, NJ, USA).
Biotolerance Biotolerance of synthesized materials was evaluated by implanting the hydrogels in rabbit eyes. Eyes of both pigmented and albino rabbits were used for each sample. Hydrogel pieces (1 mm x 5 mm x 4 mm) were implanted in anesthetized rabbit eyes by making stab incisions on the cornea with a blade. No suture was used to secure the wound. A subconjunctive injection of gentamycin (20 mg) was administered to avoid infection. Framycetin sulfate ophthalmic drops (0.5%)were placed four times a day in the operated eyes along with 0.1% dexamethazone drops for 2 weeks. Slit-lamp examination was carried out at different time intervals for YO days.
RESULTS A N D DISCUSSION
Various properties of hydrogels are tabulated in Table I. All data presented were the average of a minimum of three experiments. Hydration of hydrogels increased as the percentage of N-vinyl pyrrolidone increased in the copolymers. The specific gravity was slightly higher for the copolymer containing hydroxypropyl methacrylate. Hardness of hydrogels decreased as the amount of NVP increased in the copolymer of NVP-MMA and NVP-HPMA. The refractive index of various hydrogels increased with the increase in NVP content but was less than that of the homopolymer of NVP. All the compolymer hydrogels possessed good transmission of visible light (8Y-Y3%) as indicated in Table I. No statistically significant difference was found in the inflammatory response to a polymer hydrogel between the albino and pigmented rabbits. It was observed that NVP/MMA (65/35) copolymer implants remained transparent throughout the follow-
65 75 40 50 65 75 60 60 60
I I1 111 IV
10 20 30
35 25 60 50 35 25 30 20 10
HPMA 61.5 66.0 57.4 64.0 69.0 75.4 65.4 62.0 58.0
Water 58.7 64.8 56.2 63.0 68.1 73.8 65.0 60.0 56.5
Saline
(%I
(%I
MNA
Hydration
Monomers
1.196 1.191 1.218 1.205 1.194 1.204 1.205 1.192 1.870
Specific Gravity 84.5 78.0 77.0 74.5 70.0 69.0 79.0 81.0 83.5 =
~~
Hardness shore D
Total dose 0.55 Mrad, dose rate 56 rads/s. Amount of cross-linked EDMA copolymerization.
V VI VII VIII IX
NVP
No.
Sample
~
90 89 90 92 90 91 92 93 91
(%I
Transmission
Optical/
~
54 48 45 44 40 36 44 54 47
Contact Angle
1% of total monomer content in all
1.513 1.526 1.516 1.443 1.504 1.524 1.517 1.513 1.509
Ref. Ind.
TABLE I. Feeding Ratio and Various Physical Properties of Synthesized Hydrogels
Y
rn
5m
m
1256
SINGH ET AL
Figure 1. Anterior segment photographs of rabbit eyes after 60 days of NVP-MMA implantation; cornea crystal clear, implant transparent.
Figure 2. Anterior segment photographs of rabbit eyes after 60 days of NVP-HPMA implantation; mild fibrovascularization, implant opaque.
Figure 3. Anterior segment photographs of rabbit eyes after 60 days of N VP-HPMA-MMA implantation; anterior segment inflammation, implant translucent.
POLYMERIC HYDROGELS FOR SOFT CONTACT LENSES
1257
up period of 90 days and showed excellent biotolerance (Fig. 1). NVP/HPMA (50/50) implants turned opaque and incited a severe fibrovascular reaction with a n organized inflammatory response (Fig. 2 ) . NVP/HMPA/MMA (60/20/20) copolymer implants turned translucent but incited a milder fibrovascular reaction (Fig. 3). The control group’s eyes did not show any clinically appreciable signs of inflammation. It was found that NVP/MMA (65/35) copolymers possessed good optical qualities and the best biotolerance among the copolymers studied.
References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
11.
0. Wichterle and D. Lim, Nature, 185, 117-118 (1960). M. F. Refojo, J. Biomed. Mater. Res., 3, 333-347 (1969). M. F. Refojo and H. Yasuda, J. Appl. Polym. Sci., 9, 2425-2435 (1965). M. F. Refojo, 1. Appl. Polym. Sci., 9, 3161-3170 (1965). C. H. Dohlman, M. F. Refojo, and J. Rose, Arch. Opktkalmol., 77,252-257 (1967). H. Seiderman, U.S. Patent 3767, 731, 1973, Oct. 23. H. Seiderman, U.S. Patent 3966, 847, 1976, June, 29. U. Tanaka, Jpn. Kokai Tokyo, Koho, 7784273, 1977, July 13. S.G. Starodubtsev, 0.K. Boiko, E. A. Pavlova, and V. R. Rjabina, Kolloid. Zhurn, 44, 370-375 (1982). S. Hosaka, A. Yamada, H. Tanzawa, T. Momose, H. Magatani, and A. Nakajima, J. Biomed. Mater. Res., 14, 557-566 (1980). V. Kudela, Hydrogels, in Encyclopedia of Polymer Science and Engineering, Vol. 7, H. F. Mark et a1 (eds.), 1987, John Wiley & Sons, New York, 1987, pp. 783-803.
Received February 14, 1990 Accepted February 28, 1992
Polymeric hydrogels for soft contact lenses J. Singh, K. Agrawal, A. R. Ray, J. P. Singhal, and H. Singh* Centre for Biomedical Engineering, Indian Institute of Technology Delhi, H a m Khas, New Delki-110016. India V. K. Dada and Manoj R. Mehta Contact Lens Division, Dr. Rajendra Praskad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delki-110029, India
INTRODUCTION
The use of hydrogels for surgical implants and contact lenses was first proposed by Wichterle and Lim.’ HydrogeIs are particularly attractive for corneal lenses’ because they possess excellent optical qualities, and because they are soft and can be molded to conform to the corneal curvatures. In addition, their permeability to water and to lowmolecular-weight soluble substances can be regulated by modifying the molecular structure of the gel. Hydrogels of poly (2-hydroxyethyl methacrylate) (PHEMA)3and poly (glyceryl methacrylate) (PGMA)4 are well tolerated by the eye tissues.s N-Vinyl pyrrolidone (NVP) is the most effective comonomer used to increase the ability of HEMA hydrogels to take up more water. Several manufacturers of contact lenses use random copolymers of HEMA and NVP. Homopolymers of N-vinyl pyrrolidone have poor mechanical properties; therefore, hydrophobic monomers are used to improve mechanical properties. Contact lens materials based on copolymers of N VP, HEMA, and methacrylates have been reported by various No report is available on the preparation of NVP and hydroxypropyl methacrylate (HPMA) copolymers for contact and intraocular lenses. In the present study attempts have been made to prepare copolymers based on Nvinyl pyrrolidone, methyl methacrylate, and hydroxypropyl methacrylate for soft contact and intraocular lenses.
MATERIALS A N D METHODS
N-vinyl pyrrolidone (NVP), methyl methacrylate (MMA), and hydroxypropyl methacrylate were obtained from Fluka A.G. (Germany) and used after distillation under vacuum.” Ethylene glycol dimethacrylate (EDMA) was also obtained from Fluka AG. (Germany) and was used without any purification.
* To whom all correspondence should be addressed. Journal of Biomedical Materials Research, Vol. 26, 1253-1257 (1992) ccc 0021-9304/92/091253-05$4.00 0 1992 John Wiley & Sons, Inc.
SINGH ET AL.
1254
Methods
Copolymerization Copolymerization was carried out using a 6"Co-gamma radiation technique. Monomers with 1% EDMA were taken in ampules of 11.5 mm diameter. Monomers were degassed and ampules were sealed under vacuum. Ampules were exposed to yradiation for a total dose of 0.55 Mrad at a dose rate of 56 rads/s. After polymerization, ampules were broken and cross-linked copolymers in the form of transparent rods were obtained. Residual monomer was extracted by keeping it in boiling water for 36 h. Feeding ratios of various monomers are given in Table I. Hydration was determined by weight difference after equilibrium was reached.
Hydration
=
(Wet wt) - (dry wt) x 100 Wet wt
Specific gravity of the hydrogel was determined by dividing the weight of the specimen in air by its weight in water. Hardness was measured with a Shore D durometer according to ASTM standard D2240-75. The refractive index of hydrogels was measured with the help of an Abbe's refractometer. Transparency was measured on a UVvisible spectrophotometer (Hitachi Model 260) for visible light 0.35-0.8 pm. Wettability of hydrogels was measured by the contact angle method. The contact angle of a water drop on the surface was determined by a Goniometer Model 100-00-230 (Rame-Hart, Inc., Mountain Lakes, NJ, USA).
Biotolerance Biotolerance of synthesized materials was evaluated by implanting the hydrogels in rabbit eyes. Eyes of both pigmented and albino rabbits were used for each sample. Hydrogel pieces (1 mm x 5 mm x 4 mm) were implanted in anesthetized rabbit eyes by making stab incisions on the cornea with a blade. No suture was used to secure the wound. A subconjunctive injection of gentamycin (20 mg) was administered to avoid infection. Framycetin sulfate ophthalmic drops (0.5%)were placed four times a day in the operated eyes along with 0.1% dexamethazone drops for 2 weeks. Slit-lamp examination was carried out at different time intervals for YO days.
RESULTS A N D DISCUSSION
Various properties of hydrogels are tabulated in Table I. All data presented were the average of a minimum of three experiments. Hydration of hydrogels increased as the percentage of N-vinyl pyrrolidone increased in the copolymers. The specific gravity was slightly higher for the copolymer containing hydroxypropyl methacrylate. Hardness of hydrogels decreased as the amount of NVP increased in the copolymer of NVP-MMA and NVP-HPMA. The refractive index of various hydrogels increased with the increase in NVP content but was less than that of the homopolymer of NVP. All the compolymer hydrogels possessed good transmission of visible light (8Y-Y3%) as indicated in Table I. No statistically significant difference was found in the inflammatory response to a polymer hydrogel between the albino and pigmented rabbits. It was observed that NVP/MMA (65/35) copolymer implants remained transparent throughout the follow-
65 75 40 50 65 75 60 60 60
I I1 111 IV
10 20 30
35 25 60 50 35 25 30 20 10
HPMA 61.5 66.0 57.4 64.0 69.0 75.4 65.4 62.0 58.0
Water 58.7 64.8 56.2 63.0 68.1 73.8 65.0 60.0 56.5
Saline
(%I
(%I
MNA
Hydration
Monomers
1.196 1.191 1.218 1.205 1.194 1.204 1.205 1.192 1.870
Specific Gravity 84.5 78.0 77.0 74.5 70.0 69.0 79.0 81.0 83.5 =
~~
Hardness shore D
Total dose 0.55 Mrad, dose rate 56 rads/s. Amount of cross-linked EDMA copolymerization.
V VI VII VIII IX
NVP
No.
Sample
~
90 89 90 92 90 91 92 93 91
(%I
Transmission
Optical/
~
54 48 45 44 40 36 44 54 47
Contact Angle
1% of total monomer content in all
1.513 1.526 1.516 1.443 1.504 1.524 1.517 1.513 1.509
Ref. Ind.
TABLE I. Feeding Ratio and Various Physical Properties of Synthesized Hydrogels
Y
rn
5m
m
1256
SINGH ET AL
Figure 1. Anterior segment photographs of rabbit eyes after 60 days of NVP-MMA implantation; cornea crystal clear, implant transparent.
Figure 2. Anterior segment photographs of rabbit eyes after 60 days of NVP-HPMA implantation; mild fibrovascularization, implant opaque.
Figure 3. Anterior segment photographs of rabbit eyes after 60 days of N VP-HPMA-MMA implantation; anterior segment inflammation, implant translucent.
POLYMERIC HYDROGELS FOR SOFT CONTACT LENSES
1257
up period of 90 days and showed excellent biotolerance (Fig. 1). NVP/HPMA (50/50) implants turned opaque and incited a severe fibrovascular reaction with a n organized inflammatory response (Fig. 2 ) . NVP/HMPA/MMA (60/20/20) copolymer implants turned translucent but incited a milder fibrovascular reaction (Fig. 3). The control group’s eyes did not show any clinically appreciable signs of inflammation. It was found that NVP/MMA (65/35) copolymers possessed good optical qualities and the best biotolerance among the copolymers studied.
References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
11.
0. Wichterle and D. Lim, Nature, 185, 117-118 (1960). M. F. Refojo, J. Biomed. Mater. Res., 3, 333-347 (1969). M. F. Refojo and H. Yasuda, J. Appl. Polym. Sci., 9, 2425-2435 (1965). M. F. Refojo, 1. Appl. Polym. Sci., 9, 3161-3170 (1965). C. H. Dohlman, M. F. Refojo, and J. Rose, Arch. Opktkalmol., 77,252-257 (1967). H. Seiderman, U.S. Patent 3767, 731, 1973, Oct. 23. H. Seiderman, U.S. Patent 3966, 847, 1976, June, 29. U. Tanaka, Jpn. Kokai Tokyo, Koho, 7784273, 1977, July 13. S.G. Starodubtsev, 0.K. Boiko, E. A. Pavlova, and V. R. Rjabina, Kolloid. Zhurn, 44, 370-375 (1982). S. Hosaka, A. Yamada, H. Tanzawa, T. Momose, H. Magatani, and A. Nakajima, J. Biomed. Mater. Res., 14, 557-566 (1980). V. Kudela, Hydrogels, in Encyclopedia of Polymer Science and Engineering, Vol. 7, H. F. Mark et a1 (eds.), 1987, John Wiley & Sons, New York, 1987, pp. 783-803.
Received February 14, 1990 Accepted February 28, 1992
