Protein Drug Delivery and Formulation Development

Baid, Rinku; Tyagi, Puneet; Durazo, Shelley A.; Kompella, Uday B.

doi:10.1007/978-1-4419-9920-7_17

Cited by 4 publications

(2 citation statements)

References 110 publications

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“…(a)Topical drops must diffuse across the precorneal milieu, cornea, iris, ciliary body, and vitreous before reaching the back of the eye, severely diluting the fraction of drug reaching the retina and macula area; (b) Systemic (oral or intravenous) drug delivery, also has a poor dose-response profile for vitreoretinal targets; (c) Intravitreal injection or implant and (d) transscleral diffusion tend to increase drug proportions reaching the retina and macula area. Reprinted with permission from reference [135].…”

Section: Cataractmentioning

confidence: 99%

“…Stem cell Therapy: Emerging cell therapies for the restoration of sight have focused on two areas of the eye that are critical for visual function, the cornea and the retina [111,[135][136][137]. Current strategy for management of ocular conditions consists of eliminating the injurious agent or attempting to minimize its effects.…”

Section: Applications Of Nanoparticulate Transscleral Drug Delivery Smentioning

confidence: 99%

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Nanoparticulate Transscleral Ocular Drug Delivery

Shah¹,

Shah²,

Groshev³

et al. 2014

J Biomol Res Ther

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Ocular drug delivery is one of the most challenging areas of drug delivery due to the unique mostly avascular nature of the major eye structures and presence of two blood barriers. Effectiveness of a more conventional systemic delivery falls short due to low drug levels in the eye tissue. Periocular approaches require penetration of fibrous sclera and present their own limitations. Utilization of nanotechnology presents new avenue of drug system development with potential to penetrate protective barriers and sustain ample tissue saturation. More specifically, transscleral delivery permits a range of applications in targeted delivery, gene, stem cell, protein and peptides, oligonucleotide, and ribozyme therapies. The exciting range of current applications is expounded in this review.

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Section: Cataractmentioning

confidence: 99%

Section: Applications Of Nanoparticulate Transscleral Drug Delivery Smentioning

confidence: 99%

Nanoparticulate Transscleral Ocular Drug Delivery

Shah¹,

Shah²,

Groshev³

et al. 2014

J Biomol Res Ther

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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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