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Yu Yu, Xingyan Lin, Qilin Wang, Mingguang He, Ying Chau; In vivo evaluation of hyaluronic acid based in situ hydrogel for prolonged release of Avastin in monkey. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1973.
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To evaluate the biocompatibility and in vivo release of Avastin from a hyaluronic acid based in situ hydrogel after intravitreal injection in monkey eyes.
The in situ hydrogel is formed by the chemical crosslinking of two polymer solutions, the vinylsulfonate hyaluronic acid (HA-VS) and thiolated dextran (Dex-SH) using catalyst-free click chemistry in aqueous phase (Yu et al. 2015). The two polymers were dissolved in Avastin separately, and mixed and injected to the vitreous of monkey with 32 G needle. For comparison, native Avastin was injected to the vitreous of another group of monkeys. The total amount of Avastin injected was 1.25 mg (50ul) in both groups. The biocompatibility was evaluated by binocular indirect ophthalmoscope (BIO). The pharmacokinetics was evaluated by measuring the concentration of Avastin in aqueous humor by ELISA assay.
A transparent gel is seen in the vitreous after injection. The low viscosity of the mixture made injection easy even through 32G needle. BIO images showed that the gel does not induce hemorrhage, retinal detachment, inflammation or other gross pathological changes in monkey eye after injection (figure 1A). While the bolus intravitreal injection of native Avastin follows the first order elimination kinetics in monkey eye, the in situ gel formation was able to extend the retention of Avastin in money for at least 3 months (figure 1B).
The in situ hydrogel formulation of Avastin was transparent, biocompatible and able to prolong the retention of drug in monkey eye in vivo for multiple months.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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