Sustained Delivery of Timolol Maleate for Over 90 Days by Subconjunctival Injection

Lavik, Erin B.; Kuehn, Markus H.; Shoffstall, Andrew J.; Atkins, Kristyn T.; Dumitrescu, Alina V.; Kwon, Young H.

doi:10.1089/jop.2016.0042

Cited by 14 publications

(3 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Injections and implants release drugs within the eye and may extend the release of drug up to several weeks or months [2,[19][20][21][22]. Biodegradable implants viz.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Bimatoprost loaded nanovesicular long-acting sub-conjunctival in-situ gelling implant: In vitro and in vivo evaluation

Yadav

Guzmán-Aránguez

Lara

et al. 2019

Materials Science and Engineering: C

View full text Add to dashboard Cite

Primary treatment for glaucoma relies on chronic instillation (daily) of intraocular pressure (IOP) lowering eye drops. Present study tends to develop and assess a novel sustained release bimatoprost loaded nanovesicular (BMT-NV)-thermosensitive in-situ gelling implant (BMT-NV-GEL-IM), for subconjunctival delivery. BMT-NVs developed using novel composition and method of preparation, (IPA/700/DEL/2014) and industrially viable methodology were characterised and evaluated comprehensively for ocular suitability. Their incorporation into an in-situ gelling formula was safe (in vitro and in vivo) and stable upon sterilization. Autoclavability was an important consideration, as a preservative-free, single-use BMT-NV-GEL-IM will avoid side-effects associated with repetitive application of drops containing preservatives like benzalkonium chloride (BAK). An extended in vitro release of BMT (80.23%) was observed for 10 days while the IOP lowering effect extended over 2 months with single subconjunctival injection of BMT-NV-GEL-IM in rats. No clinical signs of irritation, inflammation, or infection were observed in any injected eye, throughout the study, as also confirmed by histology. Furthermore, single administration of BMT-NV-GEL as topical drop lowered the IOP over 5 days. Presence of significant diffuse fluorescence in confocal microscopy of internal eye tissues post-in vivo application, as subconjunctival implant, even after 2 month and eye drops upto1 week provide direct evidence of successful sustained delivery. We thus provide an

show abstract

“…Injections and implants release drugs within the eye and may extend the release of drug up to several weeks or months [2,[19][20][21][22]. Biodegradable implants viz.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Bimatoprost loaded nanovesicular long-acting sub-conjunctival in-situ gelling implant: In vitro and in vivo evaluation

Yadav

Guzmán-Aránguez

Lara

et al. 2019

Materials Science and Engineering: C

View full text Add to dashboard Cite

show abstract

“…These gels combine the benefits of solutions (accurate dosing) and gels (prolonged residence) for improved ocular bioavailability. pH-sensitive hydrogels with thermoresponsive properties, loaded with biodegradable polymer microspheres, present a novel ocular drug delivery system capable of prolonged glaucoma treatment 11 .…”

Section: Introductionmentioning

confidence: 99%

Formulation and Evaluation of Topically Retained Hydrogels Loaded with Timolol Maleate Microspheres for Extended Release in Treating Glaucoma

Ka,

et al. 2023

J. Adv. Zool.

View full text Add to dashboard Cite

Conventional aqueous eye drop formulations have a shorter retention period and wash out of the precorneal region more easily. In this study, biodegradable microsphere-loaded hydrogels were developed to extend the time of residence and improve the drug bioavailability. The prepared microspheres were fabricated using PLGA as the biodegradable polymer and PVA as the surfactant. Hydrogels were prepared using Carbopol 940 and Gellan gum as gelling agents. Methods: The microspheres were created through a technique known as double emulsion solvent evaporation method. Evaluation included for its percentage yield, entrapment efficiency, particle size and surface morphology of the prepared microspheres. Timolol Maleate microsphere loaded hydrogel underwent assessments for pH, spreadability, rheological behaviour, sterility, antimicrobial efficacy, in vitro release studies, drug release kinetics and ocular irritation. Results: FTIR analysis confirmed compatibility between the drug and polymer. SEM observations indicated spherical microspheres with sizes ranging from 1 to 12 µm, suitable for ocular application. All formulations exhibited pH values between 4.2 and 5.0, with gelation occurring at 35°C to 38°C. Formulation F3 demonstrated optimal viscosity (1486 – 1850 cps) and good spreadability. Sterility tests were successful, and F3 displayed a drug release of 82.6% after 24 hours. Antimicrobial studies exhibited inhibition zones, and ocular tests on rabbits revealed no irritation. Stability analysis indicated no significant changes in pH or clarity. Conclusion: Based on physiological, rheological, and in vitro evaluations F3 was identified as the most suitable formulation for extended Timolol Maleate release via hydrogel, holding promise for effective glaucoma treatment.

show abstract

“…2,[5][6][7] To circumvent problems with topical eye drop therapies, there has been substantial effort in developing a sustained release formulation for glaucoma therapy. For example, delivery of timolol maleate or brimonidine tartrate has been explored in the forms of microspheres, [8][9][10] nanovesicles, 11 ocular inserts, 12 contact lenses, 13 and others. Furthermore, a recent study demonstrated that sustained release of dorzolamide by biodegradable microparticles not only reduced IOP in normotensive rabbits 14 but also decreased glaucomatous retinal ganglion cell loss in a rat disease model of glaucoma.…”

Section: Introductionmentioning

confidence: 99%

Co-Delivery of Timolol and Brimonidine with a Polymer Thin-Film Intraocular Device

Samy

Cao

Kim

et al. 2019

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

Purpose: We developed a polycaprolactone (PCL) co-delivery implant that achieves zero-order release of 2 ocular hypotensive agents, timolol maleate and brimonidine tartrate. We also demonstrate intraocular pressure (IOP)-lowering effects of the implant for 3 months in vivo. Methods: Two PCL thin-film compartments were attached to form a V-shaped co-delivery device using film thicknesses of *40 and 20 mm for timolol and brimonidine compartments, respectively. In vitro release kinetics were measured in pH-and temperature-controlled fluid chambers. Empty or drug-loaded devices were implanted intracamerally in normotensive rabbits for up to 13 weeks with weekly measurements of IOP. For ocular concentrations, rabbits were euthanized at 4, 8, or 13 weeks, aqueous fluid was collected, and ocular tissues were dissected. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry. Results: In vitro studies show zero-order release kinetics for both timolol (1.75 mg/day) and brimonidine (0.48 mg/day) for up to 60 days. In rabbit eyes, the device achieved an average aqueous fluid concentration of 98.1 -68.3 ng/mL for timolol and 5.5 -3.6 ng/mL for brimonidine. Over 13 weeks, the drug-loaded co-delivery device resulted in a statistically significant cumulative reduction in IOP compared to untreated eyes (P < 0.05) and empty-device eyes (P < 0.05). Conclusions:The co-delivery device demonstrated a zero-order release profile in vitro for 2 hypotensive agents over 60 days. In vivo, the device led to significant cumulative IOP reduction of 3.4 -1.6 mmHg over 13 weeks. Acceptable ocular tolerance was seen, and systemic drug levels were unmeasurable.

show abstract

Sustained Delivery of Timolol Maleate for Over 90 Days by Subconjunctival Injection

Cited by 14 publications

References 51 publications

Bimatoprost loaded nanovesicular long-acting sub-conjunctival in-situ gelling implant: In vitro and in vivo evaluation

Bimatoprost loaded nanovesicular long-acting sub-conjunctival in-situ gelling implant: In vitro and in vivo evaluation

Formulation and Evaluation of Topically Retained Hydrogels Loaded with Timolol Maleate Microspheres for Extended Release in Treating Glaucoma

Co-Delivery of Timolol and Brimonidine with a Polymer Thin-Film Intraocular Device

Contact Info

Product

Resources

About