Performance Enhancement of Anti-Inflammatory Chitosan Oligosaccharide-Based Latanoprost Carriers by Using Sulfated Hyaluronic Acid-Functionalized Dendrimers as Targeted Drug Delivery Agents

Ocular delivery of latanoprost via eye drop formulation is one of the most commonly used treatment modalities for glaucoma. However, low bioavailability remains to be a major issue for topical drug administration. Furthermore, it has been recognized that inflammation plays a crucial role in the pathogenesis of glaucoma. Clinically, serious retinal ganglion cell death caused by inflammation can be seen in the glaucomatous patients even though the intraocular pressure is well controlled. To overcome these drawbacks, it is highly desirable to develop therapeutic drug carriers that simultaneously exhibit high anti-inflammatory activities and delivery performances, thereby offering benefits to glaucoma treatment. In this study, we hypothesize that the incorporation of sulfated hyaluronic acid-functionalized dendrimer into the chitosan oligosaccharides-based thermogels can significantly enhance drug loading and targeting as well as alleviate disease-related inflammatory response. To our knowledge, such a design has not yet been implemented, and therefore this is a new direction for further research in the development of ophthalmic biomaterials and dosage forms. This three-year project aims to investigate whether the use of sulfated hyaluronic acid-functionalized dendrimers as anti-inflammatory and targeted drug delivery agents can boost the therapeutic efficacy of injectable chitosan oligosaccharide-based thermogels as latanoprost carriers to prevent disease progression. In the first year, we will focus on the characterization and biocompatibility of synthesized chitosan oligosaccharide-based thermogels and sulfated hyaluronic acid-functionalized dendrimers. Further work over the next year will be optimization studies to evaluate the effects of level of functionalization of chitosan oligosaccharide-based thermogels and sulfated hyaluronic acid-modified dendrimers on the anti-inflammatory action and cellular targeting of drug carriers. In the final year of the study, we will pay particular attention to the examination of sulfated hyaluronic acid-functionalized dendrimers/chitosan oligosaccharide-based thermogels for intracameral targeted latanoprost delivery platform that can rescue retinal damage caused by glaucomatous inflammation. It is expected that the proposed therapeutic drug delivery system in this project will be beneficial in helping people who are experiencing vision loss.

Project ID:PB10901-0782
External Project ID:MOST107-2221-E182-058-MY3