Chitosan-Polycaprolactone Core-Shell Microparticles for Sustained Delivery of Bevacizumab.

The current therapy for treating neovascular age-related macular degeneration requires monthly intravitreal injection of angiogenesis inhibitors such as bevacizumab or ranibizumab via a 31-gauge needle to inhibit choroidal neovascularization. However, repeated intravitreal injections are associated with poor patient compliance and potential side effects. Microparticle-based injectable devices have shown great promise to address this issue by sustained delivery of protein therapeutics, but critical barriers remain, including limited loading capacity and steady long-term release without compromising the anti-angiogenic activity of drugs. Addressing these challenges, we developed a unique method for synthesizing biodegradable polymer-based core-shell microparticles with sizes around 10 µm, high physical integrity, and uniform size. Subsequent electrostatic and physical interactions to control protein diffusion were designed for the core-shell microparticles to effectively increase the capacity of drug loading to 25%, reduce burst release by almost 30%, and extend the period of drug release from 3 to 6 months. Remarkably, the microparticles enabled a longer-term drug administration and maintained high drug potency up to 6 months in vitro, representing significant advancement compared to conventional microparticle-based delivery platforms or currently commercialized devices. Additionally, the microparticles presented minimal toxicity to human retinal cells in vitro with over 90% cell viability, and they also exhibited good injection feasibility through 31-gauge needles in an ex vivo porcine eye model. These results warrant further studies to evaluate the clinical potential for treating posterior ophthalmic diseases as well as other conditions or injuries requiring long-term local drug administration.

A Hydrogel Vitreous Substitute that Releases Antioxidant.

Current experimental vitreous substitutes only replace the physical functions of the natural vitreous humor. Removal of the native vitreous disrupts oxygen homeostasis in the eye, causing oxidative damage to the lens that likely results in cataract formation. Neither current clinical treatments nor other experimental vitreous substitutes consider the problem of oxidative stress after vitrectomy. To address this problem, biomimetic hydrogels are prepared by free radical polymerization of poly(ethylene glycol) methacrylate and poly(ethylene glycol) diacrylate. These hydrogels have similar mechanical and optical properties to the vitreous. The hydrogels are injectable through small-gauge needles and demonstrate in vitro biocompatibility with human retinal and lens epithelial cells. The hydrogels and added vitamin C, an antioxidant, show a synergistic effect in protecting ocular cells against reactive oxygen species, which fulfills a chemical function of the natural vitreous. These hydrogels have the potential to prevent post-vitrectomy cataract formation and reduce the cost of additional surgeries.

Accommodative tissues influence the shape of the cornea and potentially drive corneal morphogenesis.

This study investigates whether the presence of accommodative tissues biomechanically influences the shape of the cornea and potentially drives corneal morphogenesis during embryonic ocular development. Porcine eyes were subjected to an internal pressure simulating intraocular pressure. Ocular geometry was evaluated using a corneal topographer and digital cameras before and after dissection of the accommodative tissues. A computational model of the porcine eye was constructed and loaded by an internal pressure representing intraocular pressure. Eye shape was evaluated in models with and without the ciliary body. The porcine model was generalized to the human model, simplified model, or embryonic model with different ocular tissue shapes, sizes, and stiffnesses. Experimental data showed that, even in the six-month-old pig eye, the average corneal radius of curvature increased after the removal of accommodative tissues compared to sham controls (p = 0.002). Computational results agreed with the experimental data and further suggested that the change in corneal radius is greater when the tissue stiffness is low and the intraocular pressure is high, regardless of the geometry and size of the eye components. Using a combined in vitro and in silico approach, this study explores the biomechanical influence of the accommodative tissues and related loads on the cornea and offers additional factors that might influence the shape of the cornea.