Nature-derived bionanomaterials for sustained release of 5-fluorouracil to inhibit subconjunctival fibrosis

Abstract

Abstract Effectively inhibiting subconjunctival fibrosis remains a challenge in pterygium and antiglaucoma surgery. As one of the superior first-line clinical drugs, 5-fluorouracil (5-FU) possesses certain disadvantages, such as fast drug metabolism and poor dose controllability. The emergence of appropriate pharmaceutical formulation and administration routes provides attractive solutions. In this work, we report the development of a multilevel drug release strategy using two types of nature-derived biomaterials (biocompatible chitosan and silk protein) processed into nanofibers of different size ranges, which was shown to achieve sustained release of 5-FU, toward\xa0the unique application of inhibiting subconjunctival fibrosis. In\xa0vitro data demonstrated that this system achieved fast 5-FU release during the first 25 days, where the release became relatively stable and lengthy (3 months) afterward. More importantly, the in\xa0vivo outcomes also suggested a continuous long-lasting inhibitory effect on subconjunctival myofibroblasts. These results indicated that our nature-derived bionanomaterials served as a promising drug-carrying platform for inhibiting subconjunctival fibrosis by providing sustained release of pharmaceutical compounds thus reducing the administration frequency, which may find broad utility in the treatment of ocular diseases and possibly other biomedical applications.