Abstract
Intravitreal injections are clinically established procedures in the treatment of posterior eye diseases, such as wet age-related macular degeneration (wet AMD) which requires monthly intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) protein drugs that can lead to complications due to frequent dosing. In this study, we designed a composite drug delivery system (DDS) consisting of drug-loaded poly (lactide–co–glycolide) (PLGA) nanoparticles and a chemically crosslinked hyaluronan hydrogel to reduce the dosing frequency. The morphology, size, composition, and drug loading efficiency of the prepared nanoparticles were characterized. The properties of the modified hyaluronan polymers used were also examined. The degree of swelling/degradation and controlled release ability of the hyaluronan hydrogel and the composite DDS were identified using bovine serum albumin (BSA) as a model drug. The results show that this system can retain 75% of its wet weight without losing its integrity and release the model drug at the rate of 0.4 μg/day for more than two months under physiological conditions. In addition, the nanoparticulate formulation of the system can further improve bioavailability of the drugs by penetrating deep into the retinal layers. In conclusion, the proposed composite DDS is easily prepared with biocompatible materials and is promising for providing the sustained release of the protein drugs as a better treatment for ocular neovascular diseases like wet AMD.
Highlights
Choroidal neovascularization is the main cause of wet age-related macular degeneration
Re-Vana Therapeutics have developed an in situ forming photo-crosslinkable gel-based system (OcuLief) and a preformed photo-crosslinked implant (EyeLief), which were proved to release anti-vascular endothelial growth factor (VEGF) drugs for up to 3 months [13]
This study develops a biodegradable composite drug delivery systems (DDS) consisting of PLGA nanoparticles and injectable HA hydrogel for long-term delivery of protein drugs to the posterior segment of the eye
Summary
Choroidal neovascularization is the main cause of wet age-related macular degeneration (wet AMD). The thiol-ene click reaction requires only mild conditions and needs no catalysts to proceed, forming covalent bonds between polymer chains without producing byproducts [29] Despite these advantages of in situ forming hydrogel, a fast release rate is observed when encapsulating protein drugs directly into the hydrogel. The disadvantages of individual drug delivery systems include high initial burst release, toxicity induced by particle migration, and rapid diffusion of hydrophilic protein drugs from a swelled hydrogel. This study develops a biodegradable composite DDS consisting of PLGA nanoparticles and injectable HA hydrogel for long-term delivery of protein drugs to the posterior segment of the eye. The feasibility of the sustained and prolonged release of the proposed DDS is demonstrated using bovine serum albumin (BSA) as a model drug in vitro
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