Purchase this article with an account.
Bryan Hoang, Christopher Crean, Ming Yang, Abraham Anonuevo, Ward Peterson, Jeffrey Cleland; An Injectable Depot Formulation of an Outflow Prodrug for Sustained Reduction of Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5710.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
A prodrug (GB-6249-103) of an outflow compound has been designed and synthesized by conjugating a biodegradable linker to the parent compound. The parent compound of GB-6249-103 is not amenable to sustained delivery technologies due to its physicochemical properties. Injectable polymer microparticle formulations containing GB-6249-103 have been successfully developed to enable prolonged delivery in vivo.
Physiochemical properties of GB-6249-103 were characterized in vitro, including solubility and degradation kinetics. Polymer microparticles encapsulating the prodrug were produced and fully characterized in vitro, including particle size, drug loading and drug release. Studies were conducted in pigmented rabbits to evaluate the ocular tissue distribution, clearance and tolerability of the compound released from the depot formulation after intraocular injection. The sustained effect of the released compound at lowering intraocular pressure (IOP) was also evaluated in the same animals.
In comparison to the unmodified parent compound, GB-6249-103 is substantially more hydrophobic, which makes it feasible for encapsulation in polymer microparticles. The biodegradable linker of GB-6249-103 degrades by hydrolysis and allows full conversion of GB-6249-103 to the parent compound. A pilot polymer depot formulation of GB-6249-103 has been developed and was shown to safely deliver its payload in a sustained manner both in vitro and in vivo. Significant reduction of IOP was observed within the first week following injection of the formulation in rabbits and was sustained with maximum IOP lowering of ~20% for over two months. Additional formulations with longer durations have been developed and are being evaluated in pigmented rabbits and ocular hypertensive rats.
This approach may lead to a new long-term and effective treatment for ocular hypertension through only one to two injections per year.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
This PDF is available to Subscribers Only