Development of injectable, resorbable drug-releasing copolymer scaffolds for minimally invasive sustained ophthalmic therapeutics

Scott D. Fitzpatrick; M. A. Jafar Mazumder; Benjamin Muirhead; Heather Sheardown

doi:10.1016/j.actbio.2012.03.018

Development of injectable, resorbable drug-releasing copolymer scaffolds for minimally invasive sustained ophthalmic therapeutics

Scott D. Fitzpatrick
, M. A. Jafar Mazumder
, Benjamin Muirhead
, Heather Sheardown^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

Copolymers based on N-isopropylacrylamide (NIPAAm), acrylic acid N-hydroxysuccinimide (NAS) and varying concentrations of acrylic acid (AA) and acryloyloxy dimethyl-γ-butyrolactone (DBA) were synthesized to create thermoresponsive, resorbable copolymers for minimally invasive drug and/or cell delivery to the posterior segment of the eye to combat retinal degenerative diseases. Increasing DBA content was found to decrease both copolymer water content and lower critical solution temperature. The incorporation of NAS provided an amine-reactive site, which can be exploited for facile conjugation of bioactive agents. Proton nuclear magnetic resonance analysis revealed the onset of hydrolysis-dependent opening of the DBA lactone ring, which successfully eradicated copolymer phase transition properties and should allow the gelled polymer to re-hydrate, enter systemic circulation and be cleared from the body without the production of degradation byproducts. Hydrolytic ring opening occurs slowly, with over 85% copolymer mass remaining after 130 days of incubation in 37 °C phosphate buffered saline. These slow-degrading copolymers are hypothesized to be ideal delivery vehicles to provide minimally invasive, sustained, localized release of pharmaceuticals within the posterior segment of the eye to combat retinal degenerative diseases.

Original language	English
Pages (from-to)	2517-2528
Number of pages	12
Journal	Acta Biomaterialia
Volume	8
Issue number	7
DOIs	https://doi.org/10.1016/j.actbio.2012.03.018
State	Published - Jul 2012

Bibliographical note

Funding Information:
Heather Sheardown is the founder of the 20/20 NSERC Ophthalmic Materials Network, which has ties with and receives funding from the following industrial partners: Alimera Sciences, CIBA Vision Corporation, Custom Contact Lenses, Fovea Pharmaceuticals, iCo Therapeutics, Siltech Corporation, Take Control Cosmedix, Vista Optics Limited and Walsh Medical Devices Incorporated.

Keywords

Drug delivery
N-isopropylacrylamide
Ophthalmic materials
Resorbable
Retina

ASJC Scopus subject areas

Biotechnology
Biomaterials
Biochemistry
Biomedical Engineering
Molecular Biology

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10.1016/j.actbio.2012.03.018

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title = "Development of injectable, resorbable drug-releasing copolymer scaffolds for minimally invasive sustained ophthalmic therapeutics",

abstract = "Copolymers based on N-isopropylacrylamide (NIPAAm), acrylic acid N-hydroxysuccinimide (NAS) and varying concentrations of acrylic acid (AA) and acryloyloxy dimethyl-γ-butyrolactone (DBA) were synthesized to create thermoresponsive, resorbable copolymers for minimally invasive drug and/or cell delivery to the posterior segment of the eye to combat retinal degenerative diseases. Increasing DBA content was found to decrease both copolymer water content and lower critical solution temperature. The incorporation of NAS provided an amine-reactive site, which can be exploited for facile conjugation of bioactive agents. Proton nuclear magnetic resonance analysis revealed the onset of hydrolysis-dependent opening of the DBA lactone ring, which successfully eradicated copolymer phase transition properties and should allow the gelled polymer to re-hydrate, enter systemic circulation and be cleared from the body without the production of degradation byproducts. Hydrolytic ring opening occurs slowly, with over 85\% copolymer mass remaining after 130 days of incubation in 37 °C phosphate buffered saline. These slow-degrading copolymers are hypothesized to be ideal delivery vehicles to provide minimally invasive, sustained, localized release of pharmaceuticals within the posterior segment of the eye to combat retinal degenerative diseases.",

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note = "Funding Information: Heather Sheardown is the founder of the 20/20 NSERC Ophthalmic Materials Network, which has ties with and receives funding from the following industrial partners: Alimera Sciences, CIBA Vision Corporation, Custom Contact Lenses, Fovea Pharmaceuticals, iCo Therapeutics, Siltech Corporation, Take Control Cosmedix, Vista Optics Limited and Walsh Medical Devices Incorporated. ",

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Development of injectable, resorbable drug-releasing copolymer scaffolds for minimally invasive sustained ophthalmic therapeutics

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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