The PEG-PCL-PEG Hydrogel as an Implanted Ophthalmic Delivery System after Glaucoma Filtration Surgery; a Pilot Study
Medical hypothesis discovery and innovation in ophthalmology,
Vol. 3 No. 1 (2014),
1 March 2014
,
Page 3-8
Abstract
Currently, filtration surgery has been considered as the most effective therapy for glaucoma; however, the scar formation in the surgical area may often lead to failure to the procedure. An implanted drug delivery system may provide localized and sustained release of a drug over an extended period. Poly (ethylene glycol)-poly (ε-caprolactone)-poly (ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel has been successfully synthesized and determined as thermosensitive and biocompatible. In order to overcome the limitations of common local ophthalmic medications, we investigated the function of a self-assembled PECE hydrogel as an intracameral injection-implanted drug carrier to inhibit the formation of postoperative scarring. Following intraoperative administration bevacizumab-loaded hydrogel intracameral was injected into rabbit eyes; the status of the bleb and filtration fistula formed following the filtering surgery were also examined through pathologic evaluation. Due to the sustained release of bevacizumab from the hydrogel, neovascularization and scar formation were inhibited; moreover, there were no corneal abnormalities and other ocular tissue damage found in the rabbits. This suggests that the PECE hydrogel may be considered as the novel biomaterial with potential as a sustained release system in glaucoma filtering surgery. Further studies require in shedding the light on the subject.References
Gong CY, Wu QJ, Dong PW, Shi S, Fu SZ, Guo G, Hu HZ, Zhao X, Wei YQ, Qian ZY. Acute toxicity evaluation of biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PEG-PCL-PEG hydrogel. J Biomed Mater Res B Appl Biomater. 2009 Oct;91(1):26-36. PMID: 19365823
Volotinen M, Mäenpää J, Kautiainen H, Tolonen A, Uusitalo J, Ropo A, Vapaatalo H, Aine E. Ophthalmic timolol in a hydrogel vehicle leads to minor inter-individual variation in timolol concentration in aqueous humor. Eur J Pharm Sci. 2009 Feb 15;36(2-3):292-6. PMID: 19013521
Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006 Mar;90(3):262-7. PMID: 16488940
Li Z, Van Bergen T, Van de Veire S, Van de Vel I, Moreau H, Dewerchin M, Maudgal PC, Zeyen T, Spileers W, Moons L, Stalmans I. Inhibition of vascular endothelial growth factor reduces scar formation after glaucoma filtration surgery. Invest Ophthalmol Vis Sci. 2009 Nov;50(11):5217-25. PMID: 19474408
Lattanzio FA Jr, Sheppard JD Jr, Allen RC, Baynham S, Samuel P, Samudre S. Do injections of 5-fluorouracil after trabeculectomy have toxic effects on the anterior segment? J Ocul Pharmacol Ther. 2005 Jun;21(3):223-35. PMID: 15969640.
Cui LJ, Sun NX, Li XH, Huang J, Yang JG. Subconjunctival sustained release 5-fluorouracil for glaucoma filtration surgery. Acta Pharmacol Sin. 2008 Sep;29(9):1021-8. PMID: 18718170
Horsley MB, Kahook MY. Anti-VEGF therapy for glaucoma. Curr Opin Ophthalmol. 2010 Mar;21(2):112-7. PMID: 20040875
Grewal DS, Jain R, Kumar H, Grewal SP. Evaluation of subconjunctival bevacizumab as an adjunct to trabeculectomy a pilot study. Ophthalmology. 2008 Dec;115(12):2141-2145.e2. PMID: 18692246
Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology. 2006 Mar;113(3):363-372.e5. PMID: 16458968
Davidorf FH, Mouser JG, Derick RJ. Rapid improvement of rubeosis iridis from a single bevacizumab (Avastin) injection. Retina. 2006 Mar;26(3):354-6. PMID: 16508439
Memarzadeh F, Varma R, Lin LT, Parikh JG, Dustin L, Alcaraz A, Eliott D. Postoperative use of bevacizumab as an antifibrotic agent in glaucoma filtration surgery in the rabbit. Invest Ophthalmol Vis Sci. 2009 Jul;50(7):3233-7. PMID: 19182254
Liu Z, Li J, Nie S, Liu H, Ding P, Pan W. Study of an alginate/HPMC-based in situ gelling ophthalmic delivery system for gatifloxacin. Int J Pharm. 2006 Jun 6;315(1-2):12-7. PMID: 16616442
Liu W, Griffith M, Li F. Alginate microsphere-collagen composite hydrogel for ocular drug delivery and implantation. J Mater Sci Mater Med. 2008 Nov;19(11):3365-71. PMID:18545941
Peng CL, Shieh MJ, Tsai MH, Chang CC, Lai PS. Self-assembled star-shaped chlorin-core poly(epsilon-caprolactone)-poly(ethylene glycol) diblock copolymer micelles for dual chemo-photodynamic therapies. Biomaterials. 2008 Sep;29(26):3599-608. PMID: 18572240
Miyata T, Asami N, Uragami T. A reversibly antigen-responsive hydrogel. Nature. 1999 Jun 24;399(6738):766-9. PMID: 10391240
Chao GT, Qian ZY, Huang MJ, Kan B, Gu YC, Gong CY, Yang JL, Wang K, Dai M, Li XY, Gou ML, Tu MJ, Wei YQ. Synthesis, characterization, and hydrolytic degradation behavior of a novel biodegradable pH-sensitive hydrogel based on polycaprolactone, methacrylic acid, and poly (ethylene glycol). J Biomed Mater Res A. 2008 Apr;85(1):36-46. PMID: 17688254
Chenite A, Chaput C, Wang D, Combes C, Buschmann MD, Hoemann CD, Leroux JC, Atkinson BL, Binette F, Selmani A. Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials. 2000 Nov;21(21):2155-61. PMID: 10985488
Zhu Y, Parsons SP, Huizinga JD. Measurement of intracellular chloride ion concentration in ICC in situ and in explant culture. Neurogastroenterol Motil. 2010 Jun;22(6):704-9. PMID: 20403100
Chitkara D, Shikanov A, Kumar N, Domb AJ. Biodegradable injectable in situ depot-forming drug delivery systems. Macromol Biosci. 2006 Dec 8;6(12):977-90. PMID: 17128422
Li Z, Ning W, Wang J, Choi A, Lee PY, Tyagi P, Huang L. Controlled gene delivery system based on thermosensitive biodegradable hydrogel. Pharm Res. 2003 Jun;20(6):884-8. PMID: 12817892
Lee PY, Li Z, Huang L. Thermosensitive hydrogel as a Tgf-beta1 gene delivery vehicle enhances diabetic wound healing. Pharm Res. 2003 Dec;20(12):1995-2000. PMID: 14725365
Kang Derwent JJ, Mieler WF. Thermoresponsive hydrogels as a new ocular drug delivery platform to the posterior segment of the eye. Trans Am Ophthalmol Soc. 2008;106:206-13; discussion 213-4. PMID: 19277236
Kissel T, Li Y, Unger F. ABA-triblock copolymers from biodegradable polyester A-blocks and hydrophilic poly(ethylene oxide) B-blocks as a candidate for in situ forming hydrogel delivery systems for proteins. Adv Drug Deliv Rev. 2002 Jan 17;54(1):99-134. PMID: 11755708
Liu CB, Gong CY, Huang MJ, Wang JW, Pan YF, Zhang YD, Li GZ, Gou ML, Wang K, Tu MJ, Wei YQ, Qian ZY. Thermoreversible gel-sol behavior of biodegradable PCL-PEG-PCL triblock copolymer in aqueous solutions. J Biomed Mater Res B Appl Biomater. 2008 Jan;84(1):165-75. PMID: 17455282
Yang B, Gong C, Qian Z, Zhao X, Li Z, Qi X, Zhou S, Zhong Q, Luo F, Wei Y. Prevention of post-surgical abdominal adhesions by a novel biodegradable thermosensitive PECE hydrogel. BMC Biotechnol. 2010 Sep 9;10:65. PMID: 20825683
Yang B, Gong C, Zhao X, Zhou S, Li Z, Qi X, Zhong Q, Luo F, Qian Z. Preventing postoperative abdominal adhesions in a rat model with PEG-PCL-PEG hydrogel. Int J Nanomedicine. 2012;7:547-57. PMID: 22346350
Gong C, Shi S, Dong P, Kan B, Gou M, Wang X, Li X, Luo F, Zhao X, Wei Y, Qian Z. Synthesis and characterization of PEG-PCL-PEG thermosensitive hydrogel. Int J Pharm. 2009 Jan 5;365(1-2):89-99. PMID: 18793709
Yin H, Gong C, Shi S, Liu X, Wei Y, Qian Z. Toxicity evaluation of biodegradable and thermosensitive PEG-PCL-PEG hydrogel as a potential in situ sustained ophthalmic drug delivery system. J Biomed Mater Res B Appl Biomater. 2010 Jan;92(1):129-37. PMID: 19802831
Einmahl S, Behar-Cohen F, D'Hermies F, Rudaz S, Tabatabay C, Renard G, Gurny R. A new poly (ortho ester)-based drug delivery system as an adjunct treatment in filtering surgery. Invest Ophthalmol Vis Sci. 2001 Mar;42(3):695-700. PMID: 11222529
Skuta GL, Parrish RK 2nd. Wound healing in glaucoma filtering surgery. Surv Ophthalmol. 1987 Nov-Dec;32(3):149-70. PMID: 3328315
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