@article{c7b23331166840a292889deb01870bb3,
title = "Injectable hyaluronic acid hydrogels encapsulating drug nanocrystals for long-term treatment of inflammatory arthritis",
abstract = "Antiproliferative chemotherapeutic agents offer a potential effective treatment for inflammatory arthritis. However, their clinical application is limited by high systemic toxicity, low joint bioavailability as well as formulation challenges. Here, we report an intra-articular drug delivery system combining hyaluronic acid hydrogels and drug nanocrystals to achieve localized and sustained delivery of an antiproliferative chemotherapeutic agent camptothecin for long-term treatment of inflammatory arthritis. We synthesized a biocompatible, in situ-forming injectable hyaluronic acid hydrogel using a naturally occurring click chemistry: cyanobenzothiazole/cysteine reaction, which is the last step reaction in synthesizing D-luciferin in fireflies. This hydrogel was used to encapsulate camptothecin nanocrystals (size of 160–560 nm) which released free camptothecin in a sustained manner for 4 weeks. In vivo studies confirmed that the hydrogel remained in the joint over 4 weeks. By using the collagen-induced arthritis rat model, we demonstrate that the hydrogel-camptothecin formulation could alleviate arthritis severity as indicated by the joint size and interleukin-1β level in the harvested joints, as well as from histological and microcomputed tomography evaluation of joints. The hydrogel-nanocrystal formulation strategy described here offers a potential solution for intra-articular therapy for inflammatory arthritis.",
author = "Yongsheng Gao and Douglas Vogus and Zongmin Zhao and Wei He and Vinu Krishnan and Jayoung Kim and Yujie Shi and Apoorva Sarode and Anvay Ukidve and Samir Mitragotri",
note = "Funding Information: The work was funded by the John A Paulson School of Engineering & Applied Sciences at Harvard University. The authors also thank Dr. Michael Lewandowski for the HPLC and GPC training and Dr. Michael Evans for helpful discussions. We thank Dr. Brett Geiger and Dr. Jing Yan for training on in vivo procedures. The authors thank the Wyss Institute for Biologically Inspired Engineering for their generous support of this research. This work was performed in part at the Harvard Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Coordinated Infrastructure (NSF ECCS – 1541959NSF). Samir Mitragotri is an inventor on the patent describing the hydrogel used in the study, which is licensed to Fount Bio. Samir Mitragotri a shareholder, board member, and advisor of Fount Bio. Vinu Krishnan and Douglas Vogus are shareholders of Fount Bio. Funding Information: The work was funded by the John A Paulson School of Engineering & Applied Sciences at Harvard University. The authors also thank Dr. Michael Lewandowski for the HPLC and GPC training and Dr. Michael Evans for helpful discussions. We thank Dr. Brett Geiger and Dr. Jing Yan for training on in vivo procedures. The authors thank the Wyss Institute for Biologically Inspired Engineering for their generous support of this research. This work was performed in part at the Harvard Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Coordinated Infrastructure (NSF ECCS – 1541959NSF). Samir Mitragotri is an inventor on the patent describing the hydrogel used in the study, which is licensed to Fount Bio. Samir Mitragotri a shareholder, board member, and advisor of Fount Bio. Vinu Krishnan and Douglas Vogus are shareholders of Fount Bio. Publisher Copyright: {\textcopyright} 2021 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.",
year = "2022",
month = jan,
doi = "10.1002/btm2.10245",
language = "English",
volume = "7",
journal = "Bioengineering and Translational Medicine",
issn = "2380-6761",
publisher = "John Wiley & Sons Inc.",
number = "1",
}