Purchase this article with an account.
Sara M Smith, Jacklyn H Salmon, Santhi Abbaraju, Rasidul Amin, Sidney L Weiss, Poonam Velagaleti, Ulrich Grau, Brian C Gilger; Evaluation of PTSsol for sustained topical ocular drug delivery. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4756.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Thermosensitive pentablock copolymers have previously shown to provide sustained drug release following subcutaneous, intracameral, and intravitreal injection. This study evaluated the release characteristics of brinzolamide (BRZ) from liquid pentablock copolymers (PTSsols) when applied topically through measurement of ocular residence time and reduction of intraocular pressure (IOP) in dogs.
Corneal retention time was evaluated by applying PTSsols containing NIR-labeled IgG (IRDye800CW, LICOR Biosciences, Lincoln, NE) to the corneal surface of mice and monitored by in vivo imaging (IVIS, Xenogen, Alameda, CA). The PTSsol with the longest corneal retention time was used as the vehicle for BRZ. Following measurement of baseline IOP for 5 days, normotensive dogs were dosed 3 consecutive days, with 4 untreated days between treatments: BRZ 1% in PTSsol once daily, PTSsol (blank polymer) once daily, and commercial BRZ 1% (Azopt) three times daily (tid). The right eye remained untreated. IOP was measured at 7am and 4pm for each treatment day and at 7am for two days following treatment. Ocular exams were performed daily to monitor tolerability.
PTSsol provided sustained ocular surface retention of NIR IgG. NIR IgG in saline was retained less than 3 hours, while PTSsol designated 1-0GH remained on the ocular surface for up to 21 hours and used to create a 1% BRZ PTSsol formulation. Topical PTSsol, PTSsol with BRZ 1%, and Azopt were all well tolerated, without signs of inflammation at any time point. For Azopt tid, percent reduction in IOP between the left (treated) and right (untreated) eye was significantly greater compared to baseline at the 4pm time points on each treatment day (p<0.030). Percent reduction in IOP after once daily BRZ 1% in PTSsol 1-0GH at the PM timepoints was significantly greater than at baseline for treatment days 2 and 3 (p=0.020). Although not significant, percent reduction in IOP was also greater at the AM time points each day including untreated days suggesting a sustained effect of BRZ 1% in PTSsol on IOP.
BRZ in PTSsol was well tolerated. Once daily BRZ 1% in PTSsol 1-0GH resulted in a significant IOP reduction in treated compared to untreated eyes on most treatment days. Sustained IOP lowering 24 hours post-dosing suggests that a PTSsol of BRZ at a suitable concentration may allow once/day dosing in glaucoma. Higher BRZ concentrations in PTSsols are currently being evaluated.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only