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|Title:||Shear-Associative Polymers for Ophthalmic Applications|
|Abstract:||Most existing eyedrop formulations consist primarily of dilute solutions of water-soluble polymers. While these solutions provide temporary relief of dry eye or a means to transport a drug to the cornea, dilute solutions are quickly cleared from the eye via blinking, resulting in low drug uptake and the need for multiple treatments per day. In contrast, more viscous polymer solutions can cause discomfort or irritation of the ocular surface. Highly shear-thinning polymer solutions that can flow upon the application of shear but form gels at rest and (even more ideally) act to stabilize the tear film would instead be ideal for eyedrop formulations. Poly(oligoethylene glycol methacrylate)-based hyperbranched polymers (prepared by the Strathclyde methodology using dodecanethiol as a chain transfer agent to graft hydrophobes on chain ends in a single step) represent a unique polymer building block intermediate between a nanoparticle and a linear polymer. These hyperbranched polymers exhibit shear thinning properties over at least 4 orders of magnitude in addition to a distinct internal domain with potential for drug delivery. Mixing linear, hydrophobically-modified polymers with cyclodextrin-functionalized hydrophobic-grafted hyperbranched polymers results in the formation of inclusion complexes between the hydrophobic cavity of cyclodextrin and the hydrophobic groups, introducing additional benefits in terms of generating extremely stiff gels at zero shear while maintaining the lubricity in the eye at high shear rates. In addition, dual hydrophobe-boronic acid grafted copolymers based on a poly(vinylpyrrolidone-co-vinylformamide) graft platform polymer offer significant potential as artificial tear additives. The mucoadhesive properties of phenylboronic acids (PBA) improves the bioavailability of the drugs delivered to the front of the eye with eye drops while the hydrophobic grafts on the polymer provides shear-induced lubrication for these materials.|
|Appears in Collections:||Open Access Dissertations and Theses|
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|Sahar Mokhtar-Master's Thesis.pdf||2.16 MB||Adobe PDF||View/Open|
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