Topical aldose reductase inhibitor formulations for effective lens drug delivery in a rat model for sugar cataracts

Peter F Kador, James Randazzo, Thomas Babb, Kavitha Koushik, Yoshihiro Takamura, Wenjun Zhu, Karen Blessing, Uday B. Kompella

Research output: Contribution to journalArticle

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Abstract

Purpose: In the topical delivery of drugs to the lens, drug retention on the eye surface is considered to be important because increased retention on the ocular surface should lead to increased ocular absorption of a drug through the cornea into the aqueous humor and subsequently the lens. The aim of this study was to investigate whether increasing the viscosity of a topical aldose reductase inhibitor suspension increases the lenticular bioavailability of the inhibitor and whether such a formulation can arrest sugar cataract formation. Methods: Five topical suspensions of 3% 2-methylsorbinil (2-MS) were prepared using (1) hydroxypropyl methylcellulose (HPMC, 0.5% w/v), (2) xanthan gum (0.5% w/v), (3) gellan gum (0.5% w/v), (4) carbopol (0.25% w/v), and (5) carbopol (0.25% w/v) - hydroxypropyl methylcellulose (HPMC) (0.25% w/v). Viscosity measurements were conducted with a viscometer. Lenticular levels of 2-MS were determined in the lenses from young Sprague Dawley rats receiving 1 drop of selected topical suspension twice-daily for 7 days. The efficacy of the suspensions to arrest sugar cataract formation was evaluated by administering the suspensions for 21 days to similar rats fed a diet containing 50% galactose. Lens changes were examined by portable slit lamp following mydriasis. Results: Lenticular levels of 2-MS was highest in rats administered suspensions containing 0.25% carbopol + 0.25% HPMC as vehicles followed by 0.5% gellan gum, 0.5% HPMC, 0.25% carbopol, and 0.5% xanthan gum. All untreated rats fed a 50% galactose diet developed hypermature cataracts within 15 days; however, none of the topical treated rats demonstrated cortical vacuole formation after 21 days of galactose feeding. Conclusions: In the suspensions examined, no direct relationship between the lenticular drug levels of 2-MS and either viscosity or pH of the vehicles were observed. The observed arrest of sugar cataract formation indicated that therapeutically adequate lenticular levels of 2-MS were provided by all topical suspensions.

Original languageEnglish (US)
Pages (from-to)116-123
Number of pages8
JournalJournal of Ocular Pharmacology and Therapeutics
Volume23
Issue number2
DOIs
StatePublished - Apr 1 2007

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Aldehyde Reductase
Cataract
Lenses
Suspensions
Pharmaceutical Preparations
Galactose
Viscosity
Diet
Mydriasis
Aqueous Humor
Vacuoles
Cornea
Biological Availability
Sprague Dawley Rats
Hypromellose Derivatives
carboxypolymethylene

ASJC Scopus subject areas

  • Ophthalmology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Topical aldose reductase inhibitor formulations for effective lens drug delivery in a rat model for sugar cataracts. / Kador, Peter F; Randazzo, James; Babb, Thomas; Koushik, Kavitha; Takamura, Yoshihiro; Zhu, Wenjun; Blessing, Karen; Kompella, Uday B.

In: Journal of Ocular Pharmacology and Therapeutics, Vol. 23, No. 2, 01.04.2007, p. 116-123.

Research output: Contribution to journalArticle

Kador, Peter F ; Randazzo, James ; Babb, Thomas ; Koushik, Kavitha ; Takamura, Yoshihiro ; Zhu, Wenjun ; Blessing, Karen ; Kompella, Uday B. / Topical aldose reductase inhibitor formulations for effective lens drug delivery in a rat model for sugar cataracts. In: Journal of Ocular Pharmacology and Therapeutics. 2007 ; Vol. 23, No. 2. pp. 116-123.
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abstract = "Purpose: In the topical delivery of drugs to the lens, drug retention on the eye surface is considered to be important because increased retention on the ocular surface should lead to increased ocular absorption of a drug through the cornea into the aqueous humor and subsequently the lens. The aim of this study was to investigate whether increasing the viscosity of a topical aldose reductase inhibitor suspension increases the lenticular bioavailability of the inhibitor and whether such a formulation can arrest sugar cataract formation. Methods: Five topical suspensions of 3{\%} 2-methylsorbinil (2-MS) were prepared using (1) hydroxypropyl methylcellulose (HPMC, 0.5{\%} w/v), (2) xanthan gum (0.5{\%} w/v), (3) gellan gum (0.5{\%} w/v), (4) carbopol (0.25{\%} w/v), and (5) carbopol (0.25{\%} w/v) - hydroxypropyl methylcellulose (HPMC) (0.25{\%} w/v). Viscosity measurements were conducted with a viscometer. Lenticular levels of 2-MS were determined in the lenses from young Sprague Dawley rats receiving 1 drop of selected topical suspension twice-daily for 7 days. The efficacy of the suspensions to arrest sugar cataract formation was evaluated by administering the suspensions for 21 days to similar rats fed a diet containing 50{\%} galactose. Lens changes were examined by portable slit lamp following mydriasis. Results: Lenticular levels of 2-MS was highest in rats administered suspensions containing 0.25{\%} carbopol + 0.25{\%} HPMC as vehicles followed by 0.5{\%} gellan gum, 0.5{\%} HPMC, 0.25{\%} carbopol, and 0.5{\%} xanthan gum. All untreated rats fed a 50{\%} galactose diet developed hypermature cataracts within 15 days; however, none of the topical treated rats demonstrated cortical vacuole formation after 21 days of galactose feeding. Conclusions: In the suspensions examined, no direct relationship between the lenticular drug levels of 2-MS and either viscosity or pH of the vehicles were observed. The observed arrest of sugar cataract formation indicated that therapeutically adequate lenticular levels of 2-MS were provided by all topical suspensions.",
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AU - Randazzo, James

AU - Babb, Thomas

AU - Koushik, Kavitha

AU - Takamura, Yoshihiro

AU - Zhu, Wenjun

AU - Blessing, Karen

AU - Kompella, Uday B.

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N2 - Purpose: In the topical delivery of drugs to the lens, drug retention on the eye surface is considered to be important because increased retention on the ocular surface should lead to increased ocular absorption of a drug through the cornea into the aqueous humor and subsequently the lens. The aim of this study was to investigate whether increasing the viscosity of a topical aldose reductase inhibitor suspension increases the lenticular bioavailability of the inhibitor and whether such a formulation can arrest sugar cataract formation. Methods: Five topical suspensions of 3% 2-methylsorbinil (2-MS) were prepared using (1) hydroxypropyl methylcellulose (HPMC, 0.5% w/v), (2) xanthan gum (0.5% w/v), (3) gellan gum (0.5% w/v), (4) carbopol (0.25% w/v), and (5) carbopol (0.25% w/v) - hydroxypropyl methylcellulose (HPMC) (0.25% w/v). Viscosity measurements were conducted with a viscometer. Lenticular levels of 2-MS were determined in the lenses from young Sprague Dawley rats receiving 1 drop of selected topical suspension twice-daily for 7 days. The efficacy of the suspensions to arrest sugar cataract formation was evaluated by administering the suspensions for 21 days to similar rats fed a diet containing 50% galactose. Lens changes were examined by portable slit lamp following mydriasis. Results: Lenticular levels of 2-MS was highest in rats administered suspensions containing 0.25% carbopol + 0.25% HPMC as vehicles followed by 0.5% gellan gum, 0.5% HPMC, 0.25% carbopol, and 0.5% xanthan gum. All untreated rats fed a 50% galactose diet developed hypermature cataracts within 15 days; however, none of the topical treated rats demonstrated cortical vacuole formation after 21 days of galactose feeding. Conclusions: In the suspensions examined, no direct relationship between the lenticular drug levels of 2-MS and either viscosity or pH of the vehicles were observed. The observed arrest of sugar cataract formation indicated that therapeutically adequate lenticular levels of 2-MS were provided by all topical suspensions.

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