A biodegradable ocular implant for long-term suppression of intraocular pressure

Abstract

Timolol maleate (TM) has been used for many years for the reduction of intraocular pressure (IOP) in glaucoma patients. However, the topical mode of administration (eyedrops) is far from optimal because of the issues of low bioavailability, high drug wastage, and lack of patient compliance. Suboptimal control of the IOP leads to disease progression and eventually to blindness. Ideally, TM is delivered to the patient so that its action is both localized and sustained for 3 months or more. In this work, we developed a subconjunctival TM microfilm for sustained, long-term delivery of TM to the eyes, using the biodegradable elastomer poly(lactide-co-caprolactone) (PLC). The copolymer is biocompatible and has flexibility and mechanical characteristics suitable for a patient-acceptable implant. Controlling the release of TM for 3 months is challenging, and this work describes how, by using a combination of multilayering and blending with poly(ethylene glycol) (PEG) copolymers, we were able to develop a TM-incorporated biodegradable film that can deliver TM at a therapeutic dose for 90 days in vitro. The data was further confirmed in a diseased primate model, with sustained IOP-lowering effects for 5 months with a single implant, with acceptable biocompatibility and partial degradation.

Subconjunctival Delivery of Dorzolamide-Loaded Poly(ether-anhydride) Microparticles Produces Sustained Lowering of Intraocular Pressure in Rabbits

“…38,39 Subconjunctival injection of controlled release formulations of brimonidine and timolol lowered IOP for 28 days and >4 months, respectively. 40,41 The addition of a formulation for controlled release of a CAI after subconjunctival injection adds another glaucoma treatment option. It is likely that multiple, controlled release treatment options will be needed to adequately meet clinical needs of glaucoma treatment.…”

Advances in the Design of Transdermal Microneedles for Diagnostic and Monitoring Applications

“…While the method allowed for the detection of biomarkers at the desired depth only, selectively sampling either ISF or blood, a clear signalconcentration relationship was not established, limiting this technique to qualitative analysis until further development. [64] The Kendall group has also focused on simultaneous biomarker detection, designing multiplexed MN arrays capable of detecting analyte biomarkers alongside positive and negative controls. By dividing the array into three parts and functionalizing each section with a different antibody, it was possible to semiquantitatively detect the protein rPfHRP2 (a structural protein serving as a marker of Plasmodium falciparum Small 2018, 14,1803186 infection) relative to total IgG concentration, which acted as a positive control.…”

Delivery of therapeutics for deep-seated ocular conditions – status quo

“…[36] Ocular implants allow the drug to reside at the site of action without having to deliver a large dose over a long period of time. [37] Despite these many benefits, the intravitreal administration of ocular implants does have major drawbacks, some of which include inconveniencing patients in terms of administration, risk of tissue damage and severe but rare adverse reactions such as endophthalmitis and haemorrhage. [38] In addition, high concentrations of intraocular drug delivery may lead to an increase in intraocular pressure in the eye and it may also induce local systemic adverse effects.…”