Drug-loaded and Blue-ray Filtered Hydrogel as a Potential Intraocular Lens for Cataract Treatment

Author(s): Yang Xiang, Mengwei Zou, Ying Zhang, Rongrong Jin*, Yu Nie*

Journal Name: Pharmaceutical Nanotechnology

Volume 8 , Issue 4 , 2020


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Graphical Abstract:


Abstract:

Background: Indomethacin (IND) is a class of non-steroidal, anti-inflammatory drugs, which is used to treat various kinds of ocular inflammation, and has been reported to prevent posterior capsule opacification (PCO) by inhibiting the mitosis and collagen synthesis of human lens epithelial cells (LECs). In addition, the specific absorption spectrum of indomethacin shows the effect of absorbing short-wavelength blue-violet light.

Objective: We prepared an indomethacin-loaded hydrogel as a potential intraocular lens (IOLs) material to prevent endophthalmitis, PCO and filter harmful blue light.

Methods: Indomethacin prodrugs (HEMA-IND) (HI) were prepared by esterification of indomethacin and 2-hydroxyethyl methacrylate (HEMA), and poly (HEMA-co-MAA-co-MMA-co- HI) (HAMI) hydrogels were prepared by free-radical polymerization of 2-hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA), methacrylic acid (MAA) and HI. The physical and chemical properties of obtained hydrogel were detected, including optical, morphology, thermomechanical and surface properties, equilibrium water content, drug release behaviors and cytotoxicity.

Results: HAMI hydrogels can filter harmful short-wavelength blue light and show other necessary properties like visible light transparency, glass transition temperatures, mechanical strength, and biocompatibility for making intraocular lenses. Meanwhile, MAA increases the hydrophilicity of the hydrogels, resulting in a lower water contact angle and controllable drug release from the hydrogels.

Conclusion: In summary, HAMI hydrogels show a great potential as IOL biomaterials that can maintain the sustained release of indomethacin and filter harmful blue light after cataract surgery.

Lay Summary: People with cataract surgery can be at high risk of postoperative complications, such as PCO and postoperative endophthalmitis. Moreover, early IOLs allowed all ultraviolet (UV) and visible light to pass through retina without restriction, thus to damage the retina and the retinal pigment epithelium, which may lead to retinopathy and age-related macular degeneration (AMD). Herein, we sought to design and prepare a kind of IOLs loaded with indomethacin to mitigate those postoperative complications and filter harmful blue light to improve the treatment prognosis.

Keywords: Blue-ray filtration, drug release, hydrogel, indomethacin, intraocular lens, polyacrylate.

[1]
Riaz Y, Mehta JS, Wormald R, et al. Surgical interventions for age-related cataract. Am J Ophthalmol 2007; 143(4): 733-4.
[http://dx.doi.org/10.1016/j.ajo.2007.02.015]
[2]
Parsons C, Jones DS, Gorman SP. The intraocular lens: challenges in the prevention and therapy of infectious endophthalmitis and posterior capsular opacification. Expert Rev Med Devices 2005; 2(2): 161-73.
[http://dx.doi.org/10.1586/17434440.2.2.161] [PMID: 16293053]
[3]
McCoy CP, Craig RA, McGlinchey SM, Carson L, Jones DS, Gorman SP. Surface localisation of photosensitisers on intraocular lens biomaterials for prevention of infectious endophthalmitis and retinal protection. Biomaterials 2012; 33(32): 7952-8.
[http://dx.doi.org/10.1016/j.biomaterials.2012.07.052] [PMID: 22889489]
[4]
Committee COSCSCPGE. Canadian Ophthalmological Society evidence-based clinical practice guidelines for cataract surgery in the adult eye. Can J Ophthalmol 2008; 43(Suppl. 1): S7-S57.
[http://dx.doi.org/10.3129/i08-133] [PMID: 19177161]
[5]
Awasthi N, Guo S, Wagner BJ. Posterior capsular opacification: a problem reduced but not yet eradicated. Arch Ophthalmol 2009; 127(4): 555-62.
[http://dx.doi.org/10.1001/archophthalmol.2009.3] [PMID: 19365040]
[6]
Liu YC, Wong TT, Mehta JS. Intraocular lens as a drug delivery reservoir. Curr Opin Ophthalmol 2013; 24(1): 53-9.
[http://dx.doi.org/10.1097/ICU.0b013e32835a93fc] [PMID: 23080012]
[7]
González-Chomón C, Concheiro A, Alvarez-Lorenzo C. Drug-eluting intraocular lenses. Materials (Basel) 2011; 4(11): 1927-40.
[http://dx.doi.org/10.3390/ma4111927] [PMID: 28824115]
[8]
Topete A, Serro AP, Saramago B. Dual drug delivery from intraocular lens material for prophylaxis of endophthalmitis in cataract surgery. Int J Pharm 2019; 558: 43-52.
[http://dx.doi.org/10.1016/j.ijpharm.2018.12.028] [PMID: 30630077]
[9]
Topete A, Oliveira AS, Fernandes A, Nunes TG, Serro AP, Saramago B. Improving sustained drug delivery from ophthalmic lens materials through the control of temperature and time of loading. Eur J Pharm Sci 2018; 117: 107-17.
[http://dx.doi.org/10.1016/j.ejps.2018.02.017] [PMID: 29454097]
[10]
González-Chomón C, Braga ME, de Sousa HC, Concheiro A, Alvarez-Lorenzo C. Antifouling foldable acrylic IOLs loaded with norfloxacin by aqueous soaking and by supercritical carbon dioxide technology. Eur J Pharm Biopharm 2012; 82(2): 383-91.
[http://dx.doi.org/10.1016/j.ejpb.2012.07.007] [PMID: 22846620]
[11]
Yañez F, Martikainen L, Braga ME, et al. Supercritical fluid-assisted preparation of imprinted contact lenses for drug delivery. Acta Biomater 2011; 7(3): 1019-30.
[http://dx.doi.org/10.1016/j.actbio.2010.10.003] [PMID: 20934541]
[12]
Syed Hussain S, Donempudi S, Tammishetti S, Garikapati KR, Bhadra MP. Cell adhesion resistant, UV curable, polymer zinc oxide nanocomposite materials for intraocular lens application. Polym Adv Technol 2018; 29(4): 1234-41.
[http://dx.doi.org/10.1002/pat.4234]
[13]
Parsons C, McCoy CP, Gorman SP, et al. Anti-infective photodynamic biomaterials for the prevention of intraocular lens-associated infectious endophthalmitis. Biomaterials 2009; 30(4): 597-602.
[http://dx.doi.org/10.1016/j.biomaterials.2008.10.015] [PMID: 18996591]
[14]
Tan J, Deng Z, Liu G, Hu J, Liu S. Anti-inflammatory polymersomes of redox-responsive polyprodrug amphiphiles with inflammation-triggered indomethacin release characteristics. Biomaterials 2018; 178: 608-19.
[http://dx.doi.org/10.1016/j.biomaterials.2018.03.035] [PMID: 29605185]
[15]
Nishi O, Nishi K, Yamada Y, Mizumoto Y. Effect of indomethacin-coated posterior chamber intraocular lenses on postoperative inflammation and posterior capsule opacification. J Cataract Refract Surg 1995; 21(5): 574-8.
[http://dx.doi.org/10.1016/S0886-3350(13)80220-9] [PMID: 7473123]
[16]
Nishi O, Nishi K, Fujiwara T, Shirasawa E. Effects of diclofenac sodium and indomethacin on proliferation and collagen synthesis of lens epithelial cells in vitro. J Cataract Refract Surg 1995; 21(4): 461-5.
[http://dx.doi.org/10.1016/S0886-3350(13)80541-X] [PMID: 8523295]
[17]
Zou M, Jin R, Hu Y, et al. A thermo-sensitive, injectable and biodegradable in situ hydrogel as a potential formulation for uveitis treatment. J Mater Chem B Mater Biol Med 2019; 7(28): 4402-12.
[http://dx.doi.org/10.1039/C9TB00939F]
[18]
Qandil AM. Prodrugs of nonsteroidal anti-inflammatory drugs (NSAIDs), more than meets the eye: a critical review. Int J Mol Sci 2012; 13(12): 17244-74.
[http://dx.doi.org/10.3390/ijms131217244] [PMID: 23247285]
[19]
Abioye AO, Chi GT, Kola-Mustapha AT, Ruparelia K, Beresford K. Arroo1 R. Polymer-drug nanoconjugate - an innovative nanomedicine: challenges and recent advancements in rational formulation design for effective delivery of poorly soluble drugs. Pharm Nanotechnol 2016; 4: 38-79.
[http://dx.doi.org/10.2174/2211738504666160213001714]
[20]
Jr HW.HA M. . DH S. Retinal sensitivity to damage from short wavelength light. Nature 1976; 260(5547): 260.
[21]
Henderson BA, Grimes KJ. Blue-blocking IOLs: a complete review of the literature. Surv Ophthalmol 2010; 55(3): 284-9.
[http://dx.doi.org/10.1016/j.survophthal.2009.07.007] [PMID: 20499436]
[22]
Yang H, Afshari NA. The yellow intraocular lens and the natural ageing lens. Curr Opin Ophthalmol 2014; 25(1): 40-3.
[http://dx.doi.org/10.1097/ICU.0000000000000020] [PMID: 24270599]
[23]
Bozukova D, Pagnoulle C, Jérôme R, Jérôme C. Polymers in modern ophthalmic implants-Historical background and recent advances. Mater Sci Eng Rep 2010; 69: 63-83.
[http://dx.doi.org/10.1016/j.mser.2010.05.002]
[24]
Li X, Zhao Y, Wang K, Wang L, Yang X, Zhu S. Cyclodextrin-containing hydrogels as an intraocular lens for sustained drug release. PLoS One 2017; 12(12) e0189778
[http://dx.doi.org/10.1371/journal.pone.0189778] [PMID: 29244868]
[25]
Patil S, Sandberg A, Heckert E, Self W, Seal S. Protein adsorption and cellular uptake of cerium oxide nanoparticles as a function of zeta potential. Biomaterials 2007; 28(31): 4600-7.
[http://dx.doi.org/10.1016/j.biomaterials.2007.07.029] [PMID: 17675227]
[26]
Bozukova D, Pagnoulle C, De Pauw-Gillet MC, et al. Improved performances of intraocular lenses by poly(ethylene glycol) chemical coatings. Biomacromolecules 2007; 8(8): 2379-87.
[http://dx.doi.org/10.1021/bm0701649] [PMID: 17608449]
[27]
Huang XD, Yao K, Zhang Z, Zhang Y, Wang Y. Uveal and capsular biocompatibility of an intraocular lens with a hydrophilic anterior surface and a hydrophobic posterior surface. J Cataract Refract Surg 2010; 36(2): 290-8.
[http://dx.doi.org/10.1016/j.jcrs.2009.09.027] [PMID: 20152613]
[28]
Lin Q, Tang J, Han Y, Xu X, Hao X, Chen H. Hydrophilic modification of intraocular lens via surface initiated reversible addition-fragmentation chain transfer polymerization for reduced posterior capsular opacification. Colloids Surf B Biointerfaces 2017; 151: 271-9.
[http://dx.doi.org/10.1016/j.colsurfb.2016.12.028] [PMID: 28027493]
[29]
Tan X, Zhan J, Zhu Y, et al. Improvement of uveal and capsular biocompatibility of hydrophobic acrylic intraocular lens by surface grafting with 2-metha-cryloyloxyethyl phosphorylcholine-methacrylic acid copolymer. Sci Rep 2017; 7: 40462.
[http://dx.doi.org/10.1038/srep40462] [PMID: 28084469]
[30]
Wu DQ, Qiu F, Wang T, Jiang XJ, Zhang XZ, Zhuo RX. Toward the development of partially biodegradable and injectable thermoresponsive hydrogels for potential biomedical applications. ACS Appl Mater Interfaces 2009; 1(2): 319-27.
[http://dx.doi.org/10.1021/am8000456] [PMID: 20353219]
[31]
Jung GB, Jin KH, Park HK. Physicochemical and surface properties of acrylic intraocular lenses and their clinical significance. J Pharm Investig 2017; 47(5): 453-60.
[http://dx.doi.org/10.1007/s40005-017-0323-y] [PMID: 29046825]
[32]
Wei X, She C, Chen D, et al. Blue-light-blocking intraocular lens implantation improves the sleep quality of cataract patients. J Clin Sleep Med 2013; 9(8): 741-5.
[http://dx.doi.org/10.5664/jcsm.2908] [PMID: 23946702]
[33]
Zambrowski O, Tavernier E, Souied EH, et al. Sleep and mood changes in advanced age after blue-blocking (yellow) intra ocular lens (IOLs) implantation during cataract surgical treatment: a randomized controlled trial. Aging Ment Health 2018; 22(10): 1351-6.
[http://dx.doi.org/10.1080/13607863.2017.1348482] [PMID: 28691893]
[34]
Van Den Bulcke AI, Bogdanov B, De Rooze N, Schacht EH, Cornelissen M, Berghmans H. Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromolecules 2000; 1(1): 31-8.
[http://dx.doi.org/10.1021/bm990017d] [PMID: 11709840]


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Article Details

VOLUME: 8
ISSUE: 4
Year: 2020
Published on: 08 October, 2020
Page: [302 - 312]
Pages: 11
DOI: 10.2174/2211738508666200313144112
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