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Chi Ming Laurence Lau, Ying Chau; Injectable, hydrolytically degradable hydrogel for controllable, sustained protein release in the posterior eye. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5395.
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To demonstrate the controllable, sustained release of IgG from an in-situ forming, hydrolytically degradable hydrogel in vitro.
The hydrogel is formulated by catalyst-free crosslinking of vinyl sulfone (-VS) and thiol (-SH) modified polymers in aqueous phase. The hydrolysis labile ester linkers were strategically embedded in the polymer network so that the hydrogel is degradable at physiological environment. The macroscopic bulk hydrogel degradation was controlled by ester chemistry and structural parameters of the precursor polymers, with the tunable degradation time ranged from a week to a year. The -VS and -SH functionalized polymers were dissolved in the solution of the model drug, FITC labelled IgG (150kDa, dissolved in PBS, ~pH 7.2) respectively, and mixed to form the hemispherical gels on a hydrophobic surface. The F-IgG laden hydrogels were incubated in pH 7.4 PBS at 37oC, and the in vitro cumulative drug release were profiled. The integrity of released IgG was verified using non-reducing SDS-PAGE.
The clinical relevant features of the hydrogel depot could be separately controlled by different hydrogel parameters. The polymer/drug mixtures were of low viscosity and could be easily injected with 33 gauge needles. The fraction of burst release was controlled by the polymer concentration. The period and rate of drug release were controlled by the period and rate of bulk-erosion of the hydrogel. Multi-phase release was achieved by simply mixing the hydrogel formulations. Finally, by controlling the stochastic SH/VS ratio in excess, most of the released IgG were preserved at their native form.
The injectable, hydrolytically degradable hydrogel can serve as a versatile platform for controlled, sustained release of protein therapeutics in the posterior eye as a intraocular drug depot.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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