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. 2015 Oct;5(5):469-79.
doi: 10.1007/s13346-015-0240-4.

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

Xu Wen Ng  1 , Kerh Lin Liu, Amutha Barathi Veluchamy, Nyein Chan Lwin, Tina T Wong, Subbu S Venkatraman
Affiliations

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

Xu Wen Ng et al. Drug Deliv Transl Res. 2015 Oct.

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.

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Figures

Fig. 1
Fig. 1
Release profile of 1 % TM, 1 % TB, 5 % TM, and 5 % TB PLC formulations. a Cumulative release of TM- and TB-loaded films. b Amount of TM/TB released each day. c Compilation of parameters upon fitting to the power law
Fig. 2
Fig. 2
Percentage mass loss and molecular weight change of PLC neat film, 1 % TM, 1 % TB, 5 % TM, and 5 % TB PLC formulations. a Mass loss. b Molecular weight change over 8 weeks
Fig. 3
Fig. 3
Release profiles of neat PLC, 80:20 PLC/PCL-PEG, and 90:10 PLC/PCL-PEG of 1 % TM-loaded formulations. a Cumulative release of TM. b Amount of TM released each day
Fig. 4
Fig. 4
Release profile of neat PLC, 80:20 PLC/PCL-PEG, and 90:10 PLC/PCL-PEG of 5 % TM-loaded formulations. a Cumulative release of TM. b Amount of TM released each day
Fig. 5
Fig. 5
Release profile of homogenous 80:20 PLC/PLC-PEG and sandwich of PLC- 80:20 PLC/PCL(10k)-PEG(5k) -PCL 5 % TM-loaded formulations. a Cumulative release of TM. b Amount of TM released each day; schematic cartoon of c homogenous 80:20 PLC/PLC-PEG and d sandwich of PLC- 80:20 PLC/PCL(10k)-PEG(5k) -PCL 5 % TM-loaded formulations
Fig. 6
Fig. 6
Release profile of sandwich 80:20 PLC/PLC-PEG (5 k) 20 % TM-loaded formulations. a Cumulative release of TM. b Amount of TM released each day. c Schematic of construct and release profile of sandwich 80:20 PLC/PLC-PEG (1 k) 20 % TM-loaded formulations. d Cumulative release of TM. e Amount of TM released each day. f Schematic of construct
Fig. 7
Fig. 7
Comparison between groups with TM eyedrop treatment and TM implant treatment. a Intraocular pressure (IOP) and b percentage reduction of IOP
Fig. 8
Fig. 8
a Slit lamp photographs of subconjunctivally implanted TM microfilms and the eyedrop treatment group at 1 month, 3 months, and 5 months after treatment. b Implant was noted at 0 day, 1 month, 3 months, 5 months, and 8 months after insertion
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