Development of Therapeutic Nanoconnectors for Keratoconic Corneal Tissue Repair

This project will be devoted to the development of biomaterial nanotherapeutics as a new eye drop formulation for keratoconus treatment, which is closely related to the research field of “Biomedical engineering”. Keratoconus is a bilateral ectatic disease characterized by corneal thinning and protrusion, which results in blurred vision. Given that keratoconus is known to be the result of focal weakening of cornea associated with oxidative stress-induced degradation of stromal collagen and loss of stromal tissue, the clinician adopts a technique of riboflavin/ultraviolet-A-mediated collagen cross-linking for the treatment of keratoconus. However, this approach has some drawbacks that motivate us to develop efficient therapies to arrest keratoconus disease progression to end-stage requiring corneal transplantation. Although its etiology is still poorly understood, keratoconus is recently found to be associated with an inflammatory process. There is an urgent need to consider the architectural reinforcement of keratoconic cornea while simultaneously improving pathological factors (i.e., oxidative stress/proinflammatory signaling) within the ocular environment. From the perspective of practical use, ocular administration of therapeutics via eye drops is always a preferred way for patients. Nevertheless, topical medication instillation is known to be severely limited by poor bioavailability due to static and dynamic ocular barriers. To circumvent these drawbacks, herein, the project aims to design and develop multifunctional therapeutic nanoconnectors for topical eye drop administration in the treatment of keratoconus. Our hypothesis is that the combination of the features of tight junction opening, antioxidation/antiinflammation, structural reinforcement, and matrix production/phenotypic maintenance of the collagen mimetic peptide (POG)/chitosan-gallic acid (CSGA)-functionalized hyaluronic acid succinimidyl succinate (HA-NHS) will improve pharmacological bioavailability and therapeutic efficacy of topical ocular nanomedicine. Compared with traditional treatment modality involving riboflavin/ultraviolet-A-induced corneal collagen cross-linking for keratoconus, the topical administration of multifunctional therapeutic nanoconnectors can exhibit better performance in tissue repair and functional recovery by fully alleviating pathological manifestations and structural abnormalities occurring in the keratoconic cornea. To test these hypotheses, we will focus on the characterization and cytocompatibility of therapeutic nanoconnectors in the first year of this project. Further work over the next year will be ocular tolerability and functional assessment of nanoconnectors. Studies in the final year will allow us to learn more about therapeutic efficacies of multifunctional nanoconnectors in an experimental keratoconus model. The novel ocular nanomedicine will help people who are experiencing vision loss.

Project ID:PG11101-0005
External Project ID:NHRI-EX111-11128EI