Delivery strategies for treatment of age-related ocular diseases: From a biological understanding to biomaterial solutions

Delplace, Vianney; Payne, Samantha L.; Shoichet, Molly S.

doi:10.1016/j.jconrel.2015.09.065

Cited by 69 publications

(41 citation statements)

References 224 publications

(276 reference statements)

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“…While IVT injections are the best way to administer a reproducible dose of an antibody to the back of the eye, clinical practice is hampered by the need for IVT injections of these medicines every 1–2 months. To better treat chronic blinding conditions, there is a need to develop ocular formulations that could maintain a therapeutic dose of a medicine in the vitreous cavity for longer periods of time …”

Section: Introductionmentioning

confidence: 99%

Comparative Study of In Situ Loaded Antibody and PEG‐Fab NIPAAM Gels

Awwad

Al-Shohani

Khaw

et al. 2017

Macromolecular Bioscience

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Hydrogels can potentially prolong the release of a therapeutic protein, especially to treat blinding conditions. One challenge is to ensure that the protein and hydrogel are intimately mixed by better protein entanglement within the hydrogel. N-isopropylacrylamide (NIPAAM) gels are optimized with poly(ethylene glycol) diacrylate (PEDGA) crosslinker in the presence of either bevacizumab or PEG conjugated ranibizumab (PEG -Fab ). The release profiles of the hydrogels are evaluated using an outflow model of the eye, which is previously validated for human clearance of proteins. Release kinetics of in situ loaded bevacizumab-NIPAAM gels displays a prolonged bimodal release profile in phosphate buffered saline compared to bevacizumab loaded into a preformed NIPAAM gel. Bevacizumab release in simulated vitreous from in situ loaded gels is similar to bevacizumab control indicating that diffusion through the vitreous rather than from the gel is rate limiting. Ranibizumab is site-specifically PEGylated by disulfide rebridging conjugation. Prolonged and continuous release is observed with the in situ loaded PEG -Fab -NIPAAM gels compared to PEG -Fab injection (control). Compared to an unmodified protein, there is better mixing due to PEG entanglement and compatibility of PEG -Fab within the NIPAAM-PEDGA hydrogel. These encouraging results suggest that the extended release of PEGylated proteins in the vitreous can be achieved using injectable hydrogels.

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Section: Introductionmentioning

confidence: 99%

Comparative Study of In Situ Loaded Antibody and PEG‐Fab NIPAAM Gels

Awwad

Al-Shohani

Khaw

et al. 2017

Macromolecular Bioscience

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“…Posterior segment ocular diseases are a leading cause of visual impairment and blindness in the aging societies . Due to the specific barriers of the eye, these diseases are commonly treated by intravitreal injections every 4–8 weeks . Sustained release systems have been proposed to prolong the intravitreal injection intervals and to deliver drugs at controlled levels over prolonged periods of time.…”

Section: Introductionmentioning

confidence: 99%

“…Sustained release systems have been proposed to prolong the intravitreal injection intervals and to deliver drugs at controlled levels over prolonged periods of time. These systems usually consist of either polymer particles or solid polymer implants . A water soluble delivery vehicle could overcome certain limitations associated with particles or implants, such as visual disturbances, aggregation, increased ocular pressure and other adverse ocular effects .…”

Section: Introductionmentioning

confidence: 99%

“…[1,2] Due to the specific barriers of the eye, these diseases are commonly treated by intravitreal injections every 4-8 weeks. [3][4][5] Sustained release systems have been proposed to prolong the intravitreal injection intervals and to deliver drugs at controlled levels over prolonged periods of time. These systems usually consist of either polymer particles or solid polymer implants.…”

Section: Introductionmentioning

confidence: 99%

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Hyaluronic Acid Graft Copolymers with Cleavable Arms as Potential Intravitreal Drug Delivery Vehicles

Borke

Najberg

Ilina

et al. 2017

Macromolecular Bioscience

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Treatment of retinal diseases currently demands frequent intravitreal injections due to rapid clearance of the therapeutics. The use of high molecular weight polymers can extend the residence time in the vitreous and prolong the injection intervals. This study reports a water soluble graft copolymer as a potential vehicle for sustained intravitreal drug delivery. The copolymer features a high molecular weight hyaluronic acid (HA) backbone and poly(glyceryl glycerol) (PGG) side chains attached via hydrolysable ester linkers. PGG, a polyether with 1,2‐diol groups in every repeating unit available for conjugation, serves as a detachable carrier. The influence of synthesis conditions and incubation in physiological media on the molecular weight of HA is studied. The cleavage of the PGG grafts from the HA backbone is quantified and polymer‐from‐polymer release kinetics are determined. The biocompatibility of the materials is tested in different cell cultures.

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“…However, the use of eye drops has not necessarily been considered a treatment option due to the assumption that drugs delivered by this manner do not reach the retina and choroid. Growing research into biomaterials and nanotechnology for novel methods of delivery to treat ocular neovascularization and vascular permeability is currently underway, albeit in early stages of development (18).…”

mentioning

confidence: 99%