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Academic Journal
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Lavik E; 1 Department of Chemical, Biochemical, and Environmental Engineering, University of Maryland-Baltimore County , Baltimore, Maryland.
Kuehn MH; 2 Department of Ophthalmology and Visual Sciences, The University of Iowa , Iowa City, Iowa.; 3 Iowa City Veterans Affairs Center for the Prevention and Treatment of Visual Loss , Iowa City, Iowa.
Shoffstall AJ; 4 Department of Biomedical Engineering, Case Western Reserve University , Cleveland, Ohio.
Atkins K; 4 Department of Biomedical Engineering, Case Western Reserve University , Cleveland, Ohio.
Dumitrescu AV; 2 Department of Ophthalmology and Visual Sciences, The University of Iowa , Iowa City, Iowa.
Kwon YH; 2 Department of Ophthalmology and Visual Sciences, The University of Iowa , Iowa City, Iowa. -
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics [J Ocul Pharmacol Ther] 2016 Dec; Vol. 32 (10), pp. 642-649. Date of Electronic Publication: 2016 Nov 11.
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English
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Purpose: Medical treatment of glaucoma relies on intraocular pressure (IOP)-lowering medications, typically administered daily by the patient. While these medications are effective when applied correctly, patient adherence is a major obstacle in glaucoma treatment. We have developed a sustained-release formulation of timolol maleate that can be injected subconjunctivally to avoid patient noncompliance.
Methods: A biodegradable microsphere formulation for timolol maleate was injected subconjunctivally in normal rabbits. We measured timolol levels in tears, aqueous humor, vitreous humor, and serum of study rabbits. Furthermore, IOP profiles were recorded longitudinally. Tissue compatibility and side effects were evaluated using histochemistry.
Results: The microsphere formulation led to measureable amounts of timolol in the aqueous humor and the tear film for up to 90 days. Timolol was not detectable in the serum at any time. A significant reduction of IOP was observed in treated eyes. Clinically, the subconjunctival administration of the microspheres was well tolerated with no signs of inflammation or infection. The absence of local inflammation was confirmed by histology.
Conclusions: A single subconjunctival administration of timolol microspheres achieved delivery and IOP reduction in rabbits for up to 90 days without local or systemic inflammation or toxicity. This approach has the potential to improve the management of glaucoma in patient populations, who are challenged to adhere to a regimen of daily eye drops.
Competing Interests: Author Disclosure Statement No competing financial interests exist.
Additional Information
Publisher: Association For Ocular Pharmacology And Therapeutics Country of Publication: United States NLM ID: 9511091 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-7732 (Electronic) Linking ISSN: 10807683 NLM ISO Abbreviation: J Ocul Pharmacol Ther Subsets: MEDLINE
Publication: New York, NY : Association For Ocular Pharmacology And Therapeutics
Original Publication: New York, NY : The Association, c1995-
Original Publication: New York, NY : The Association, c1995-
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Drug Deliv. 2011 Sep-Oct;18(7):502-10. (PMID: 21790329)
J Ocul Pharmacol Ther. 1996 Winter;12(4):471-80. (PMID: 8951683)
Br J Ophthalmol. 1998 Jun;82(6):630-3. (PMID: 9797662)
Invest Ophthalmol Vis Sci. 1984 Mar;25(3):374-7. (PMID: 6698755)
Eur J Pharmacol. 2013 Feb 15;701(1-3):213-7. (PMID: 23270715)
Am J Ophthalmol. 2002 Jun;133(6):764-72. (PMID: 12036667)
Int J Pharm. 2004 Mar 19;272(1-2):91-8. (PMID: 15019072)
J Microencapsul. 2009 Feb;26(1):18-26. (PMID: 18465288)
J Ocul Pharmacol Ther. 1996 Fall;12(3):245-52. (PMID: 8875330)
ACS Nano. 2014 Jan 28;8(1):419-29. (PMID: 24392729)
Am J Public Health. 1993 May;83(5):711-6. (PMID: 8484454)
Int J Pharm. 2014 Oct 20;474(1-2):103-11. (PMID: 25148727)
Drug Deliv Transl Res. 2015 Oct;5(5):469-79. (PMID: 26100093)
J Control Release. 2015 Dec 28;220(Pt B):584-91. (PMID: 26363300)
J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Nov 15;879(30):3434-43. (PMID: 21963479)
Arch Ophthalmol. 2009 Aug;127(8):1043-7. (PMID: 19667343)
Drugs Aging. 2005;22(1):1-21. (PMID: 15663346)
J Ocul Pharmacol Ther. 2012 Aug;28(4):350-8. (PMID: 22320419)
Br J Ophthalmol. 2006 Mar;90(3):262-7. (PMID: 16488940)
J Ocul Pharmacol Ther. 2005 Dec;21(6):445-53. (PMID: 16386086)
Int J Pharm. 2002 Jul 8;241(1):47-55. (PMID: 12086720)
Exp Eye Res. 2014 Apr;121:86-93. (PMID: 24561115)
Clin Ther. 2000 Feb;22(2):167-208. (PMID: 10743979)
Graefes Arch Clin Exp Ophthalmol. 2006 Nov;244(11):1491-6. (PMID: 16628416)
J Microencapsul. 1999 Nov-Dec;16(6):687-96. (PMID: 10575621)
Biomaterials. 2014 Jan;35(1):432-9. (PMID: 24094935)
J Ocul Pharmacol Ther. 2009 Dec;25(6):551-3. (PMID: 20028263)
N Engl J Med. 2009 Mar 12;360(11):1113-24. (PMID: 19279343)
Invest Ophthalmol Vis Sci. 1977 Nov;16(11):987-96. (PMID: 21145)
Invest Ophthalmol Vis Sci. 2008 Jan;49(1):320-32. (PMID: 18172109)
J Pharm Sci. 2002 Oct;91(10):2182-92. (PMID: 12226845)
Eye Contact Lens. 2014 Sep;40(5):269-76. (PMID: 25162288)
J Ocul Pharmacol Ther. 2013 Mar;29(2):229-35. (PMID: 23205896)
Biol Pharm Bull. 2008 May;31(5):970-5. (PMID: 18451528)
J Glaucoma. 2010 Aug;19(6):356-64. (PMID: 20179619)
J Drug Target. 2004 Jan;12(1):19-24. (PMID: 15203908)
Curr Eye Res. 2012 Mar;37(3):204-11. (PMID: 22335807)
Invest Ophthalmol Vis Sci. 2013 Aug 19;54(8):5629-37. (PMID: 23868986)
Invest Ophthalmol Vis Sci. 2011 Jun 01;52(6):3548-56. (PMID: 21296826)
J Ocul Pharmacol Ther. 2005 Dec;21(6):436-44. (PMID: 16386085)
Curr Opin Ophthalmol. 2014 Mar;25(2):112-7. (PMID: 24463419)
J Control Release. 2013 Jan 10;165(1):82-9. (PMID: 23123188)
Am J Ophthalmol. 2005 Oct;140(4):598-606. (PMID: 16226511)
J Control Release. 2016 Mar 28;226:47-56. (PMID: 26860285)
Invest Ophthalmol Vis Sci. 2009 Oct;50(10):4807-13. (PMID: 19324856)
Exp Eye Res. 2013 Jul;112:29-36. (PMID: 23603320)
Can J Ophthalmol. 1984 Feb;19(1):2-5. (PMID: 6608974)
N Engl J Med. 1998 Oct 29;339(18):1298-307. (PMID: 9791148)
Exp Eye Res. 2008 Aug;87(2):89-95. (PMID: 18572163)
Eye (Lond). 1998;12 ( Pt 2):234-6. (PMID: 9683946)
Ophthalmol Clin North Am. 2005 Sep;18(3):383-95, vi. (PMID: 16054996)
Int J Pharm Investig. 2014 Jul;4(3):112-8. (PMID: 25126524)
Drug Deliv. 2011 Sep-Oct;18(7):502-10. (PMID: 21790329)
J Ocul Pharmacol Ther. 1996 Winter;12(4):471-80. (PMID: 8951683)
Br J Ophthalmol. 1998 Jun;82(6):630-3. (PMID: 9797662)
Invest Ophthalmol Vis Sci. 1984 Mar;25(3):374-7. (PMID: 6698755)
Eur J Pharmacol. 2013 Feb 15;701(1-3):213-7. (PMID: 23270715)
Am J Ophthalmol. 2002 Jun;133(6):764-72. (PMID: 12036667)
Int J Pharm. 2004 Mar 19;272(1-2):91-8. (PMID: 15019072)
J Microencapsul. 2009 Feb;26(1):18-26. (PMID: 18465288)
J Ocul Pharmacol Ther. 1996 Fall;12(3):245-52. (PMID: 8875330)
ACS Nano. 2014 Jan 28;8(1):419-29. (PMID: 24392729)
Am J Public Health. 1993 May;83(5):711-6. (PMID: 8484454)
Int J Pharm. 2014 Oct 20;474(1-2):103-11. (PMID: 25148727)
Drug Deliv Transl Res. 2015 Oct;5(5):469-79. (PMID: 26100093)
J Control Release. 2015 Dec 28;220(Pt B):584-91. (PMID: 26363300)
DP2 OD007338 United States OD NIH HHS
Keywords: glaucoma pharmacology; rabbit; sustained delivery; timolol maleate
0 (Delayed-Action Preparations)
817W3C6175 (Timolol)
817W3C6175 (Timolol)
Date Created: 20161112 Date Completed: 20171106 Latest Revision: 20181113
20221216
PMC5165680
10.1089/jop.2016.0042
27835065