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

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

doi:10.1016/j.actbio.2012.03.018

Cited by 27 publications

(18 citation statements)

References 25 publications

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“…However, posterior segment disorders are normally chronic disorders with a requirement for multiple injections to achieve therapeutic effects. This necessitated multiple injections, which were inconvenient for patients, increased healthcare costs, and were associated with high risk of complications such as endophthalmitis, retinal detachment, vitreous hemorrhage, and cataract (Bochot and Fattal 2012;Fitzpatrick et al, 2012;Kaur and Kakkar 2014). Therefore, the development of a sustained release system that could lead to controlled and localized delivery of therapeutic concentrations of drug without frequent administration, using the intraocular route, is very meaningful.…”

Section: Introductionmentioning

confidence: 98%

An injectable thermosensitive polymeric hydrogel for sustained release of Avastin® to treat posterior segment disease

Xie

Jin

Luo

et al. 2015

International Journal of Pharmaceutics

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Section: Introductionmentioning

confidence: 98%

An injectable thermosensitive polymeric hydrogel for sustained release of Avastin® to treat posterior segment disease

Xie

Jin

Luo

et al. 2015

International Journal of Pharmaceutics

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“…Due to the small size of the subretinal compartment, the fabricated scaffold must be extremely thin [47] and should be implantable using a minimally invasive technique [48,49]. The scaffold material must be mechanically strong to withstand the necessary surgical manipulation, and also flexible to avoid damage to the surrounding tissue [50], and it also should provide sufficient signals for proper cell attachment and alignment.…”

Section: Substrate Materials Fabrication Techniques and Specific Promentioning

confidence: 99%

“…p107 single horizontal interneurons, but not other types of retinal neurons, proliferated in the BM sponge in a 3-D manner [64]. Fitzpatrick et al [65] synthesized two thermoresponsive, bioactive cell scaffolds by decorating the backbone of type I bovine collagen with linear chains of poly(Nisopropylacrylamide) (PNIPAAm), with the ultimate aim of providing delivery via injection of RPE cells into the back of the eye for the treatment of retinal degenerative diseases [65]. Treharne et al [66] developed an electrospun fibrous scaffold derived from methyl methacrylate and polyethylene glycol methacrylate as a scaffold for delivery of the RPE.…”

Section: Substrates and Scaffolds For Retinal Cell Deliverymentioning

confidence: 99%

Approaches to Cell Delivery: Substrates and Scaffolds for Cell Therapy

Kundu

Michaelson²,

Baranov³

et al. 2014

Developments in Ophthalmology

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Retinal degeneration, associated with loss of photoreceptors, is the primary cause of permanent vision impairment, impacting millions of people worldwide. Age-related macular degeneration and retinitis pigmentosa are two common retinal diseases resulting in photoreceptor loss and vision impairment or blindness. Presently, available treatments can only delay the progress of retinal degeneration, and there are no treatments that can restore permanent vision loss. Research is underway to develop methods of regenerating the impaired retina by delivering photoreceptor precursor cells and retinal pigment epithelium to the subretinal space. Challenges to cell transplantation include limited survival upon implantation and the formation of abnormal cell architectures in vivo. Retinal tissue engineering shows immense promise and potential in treatment of retinal degeneration by employing scaffold-based delivery systems of retinal progenitor cells to the subretinal space. Scaffold delivery strategy has been shown to enhance the cell survival and direct cell differentiation in a variety of retinal degenerative models. In this chapter, we summarize the research findings on different scaffold- or substrate-based transplantation techniques used to deliver retinal progenitor/photoreceptor precursors and retinal pigment epithelial cells to the subretinal space.

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“…To meet the demand of improved IVIs the Sheardown group has previously developed poly(N‐isopropylacrylamide) (pNIPAAm) based copolymers capable of in situ gelation upon injection into the vitreous for the sustained release of Dex . pNIPAAm is a thermoresponsive polymer that undergoes a rapid transition from liquid to hydrogel phase upon heating above its lower critical solution temperature (LCST) of ∼32

°

C .…”

Section: Introductionmentioning

confidence: 99%

Tunable release of ophthalmic therapeutics from injectable, resorbable, thermoresponsive copolymer scaffolds

2015

Self Cite

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The sustained release of ophthalmic therapeutics to the posterior segment of the eye is a challenge. Injectable polymer materials have the potential to reduce injection frequency by providing long term therapeutic delivery. Copolymers with varying N-isopropylacrylamide, acrylamide (AAm), acrylic acid N-hydroxysuccinimide, and (r)-α-acryloyloxy-β,β-dimethyl-γ-butyrolactone (DBA) were synthesized by RAFT polymerization to develop injectable, resorbable, and thermoresponsive copolymer scaffolds. Upon injection into physiological conditions, these copolymers undergo a temperature induced gelation to form a drug releasing scaffold. Modification of the copolymer's AAm/DBA ratio and molecular weight afforded significant and precise control over the scaffold's physical properties and subsequent drug release profile. Hydrolytic DBA ring-opening enables redissolution of the copolymers for clearance from the body. Precise control over the drug release profile from these copolymer scaffolds by simple alteration of composition and molecular weight provides an efficient method to customize the minimally invasive delivery of therapeutics to the posterior segment of the eye. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 53-62, 2017.

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

Cited by 27 publications

References 25 publications

An injectable thermosensitive polymeric hydrogel for sustained release of Avastin® to treat posterior segment disease

An injectable thermosensitive polymeric hydrogel for sustained release of Avastin® to treat posterior segment disease

Approaches to Cell Delivery: Substrates and Scaffolds for Cell Therapy

Tunable release of ophthalmic therapeutics from injectable, resorbable, thermoresponsive copolymer scaffolds

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