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

Ng XW, Liu KL, Veluchamy AB, Lwin NC, Wong TT, Venkatraman SS - Drug Deliv Transl Res (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Materials Science and Engineering, Nanyang Technological University, Block N4.1-02-06, Nanyang Avenue, Singapore, 639798, Singapore.

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.

No MeSH data available.


Related in: MedlinePlus

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
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Fig3: 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

Mentions: Again, contrary to expectation, the release was actually higher for the blended than the neat film (Fig. 3a). Moreover, the burst release increased with increasing blending ratio (for example, the 10 % PCL-PEG blend formulation had a burst release of 9.3 % while the 20 % PCL-PEG blend had 15.8 % release on day 1). Following the initial release, the 20 % PCL-PEG blend showed average daily release amounts of 0.7 ± 0.6 μg for 76 days (Fig. 3b).Fig. 3


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

Ng XW, Liu KL, Veluchamy AB, Lwin NC, Wong TT, Venkatraman SS - Drug Deliv Transl Res (2015)

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
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4551556&req=5

Fig3: 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
Mentions: Again, contrary to expectation, the release was actually higher for the blended than the neat film (Fig. 3a). Moreover, the burst release increased with increasing blending ratio (for example, the 10 % PCL-PEG blend formulation had a burst release of 9.3 % while the 20 % PCL-PEG blend had 15.8 % release on day 1). Following the initial release, the 20 % PCL-PEG blend showed average daily release amounts of 0.7 ± 0.6 μg for 76 days (Fig. 3b).Fig. 3

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Materials Science and Engineering, Nanyang Technological University, Block N4.1-02-06, Nanyang Avenue, Singapore, 639798, Singapore.

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.

No MeSH data available.


Related in: MedlinePlus