A microinjection device for delivering in situ-gelling hydrogels for posterior segment drug delivery

摘要

?Purpose?Several posterior segment diseases (e.g. wet AMD) are now routinely treated via intraocular injections. However, the required frequency of injections greatly increases the risk of complications over time. Hydrogels that gel in situ upon injection via a rapid chemical reaction between two functionalized polymers offer a potential solution, as they can facilitate sustained drug release kinetics while remaining transparent and degradable. However, to assess the in vivo capabilities of such hydrogels in the eye, very small volumes of each reactive material (1-10μL) must be injected. While this is facilely done with single component systems, no suitable system exists for the administration of in situ-gelling hydrogels at such low volumes. ?Methods?A microinjector has been developed that is able to mix two reactive polymers and controllably, rapidly, and precisely inject volumes of 1-10 μL through a narrow gauge needle suitable for ophthalmic applications. The device design (Figure 1a) consists of a double barrel syringe connected to two separate inlets of a microfluidic chip (Figure 1c), a serpentine mixing channel with grooves to promote mixing, and a volume control reservoir with a one-way valve attached to a second syringe that pushes the mixed polymer solutions out the needle (into the eye) (Figure 1b). ?Results?The materials are fully mixed after a short distance in the mixing channel, with optimum channel lengths determined for various reactive polymer combinations. With the volume control chamber and the one-way flow valve, the device is able to eject droplets with controlled volumes (~±10%) in the range of interest (1-10 μL) via an entirely handheld operation, requiring no additional equipment. Hydrogel droplets can be formed by injection through 33G needles and capillaries into various materials, including bovine vitreous humor at 37°C. The devices have been designed for ease of use within in vivo mouse eye injections, the results of which will be discussed. ?Conclusions?The ability to inject small amounts of in situ-gelling hydrogel precursors via a microinjection device allows for in vivo use of injectable hydrogels as ocular drug delivery materials, enabling clinical exploitation of the favorable properties of such materials for ophthalmic drug delivery. ?View OriginalDownload Slide?Figure 1: (a) microinjector device design; (b) ejection of a 2μL droplet; (c) handheld operation with two syringes?Figure 1: (a) microinjector device design; (b) ejection of a 2μL droplet; (c) handheld operation with two syringesView OriginalDownload Slide? Keywords: 412 age-related macular degeneration ? 764 vitreous substitutes ? 608 nanomedicine ?.