Identification of formulation parameters that affect the analgesic efficacy of ProGel-Dex - A thermoresponsive polymeric dexamethasone prodrug for chronic arthritis pain relief.

Autor:	Wei X; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Zhao G; Ensign Pharmaceutical, Inc., Omaha, NE 68106, USA., Chen N; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Xu X; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Jiang H; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Tran D; Ensign Pharmaceutical, Inc., Omaha, NE 68106, USA., Glissmeyer E; Ensign Pharmaceutical, Inc., Omaha, NE 68106, USA., Goldring MB; Hospital for Special Surgery, New York, NY 10021, USA., Goldring SR; Ensign Pharmaceutical, Inc., Omaha, NE 68106, USA; Hospital for Special Surgery, New York, NY 10021, USA., Wang D; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Ensign Pharmaceutical, Inc., Omaha, NE 68106, USA; Department of Orthopaedic Surgery & Rehabilitation, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: dwang@unmc.edu.
Jazyk:	angličtina
Zdroj:	Nanomedicine : nanotechnology, biology, and medicine [Nanomedicine] 2024 Nov; Vol. 62, pp. 102782. Date of Electronic Publication: 2024 Aug 22.
DOI:	10.1016/j.nano.2024.102782
Abstrakt:	The relief of joint pain is one of the main objectives in the clinical management of arthritis. Although significant strides have been made in improving management of rheumatoid and related forms of inflammatory arthritis, there are still major unmet needs for therapies that selectively provide potent, sustained and safe joint pain relief, especially among patients with osteoarthritis (OA), the most common form of arthritis. We have recently developed ProGel-Dex, an N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based thermoresponsive dexamethasone (Dex) prodrug, which forms a hydrogel upon intra-articular administration and provides sustained improvement in pain-related behavior and inflammation in rodent models of arthritis. The focus of the present study was to investigate the impact of ProGel-Dex formulation parameters on its physicochemical properties and in vivo efficacy. The results of this study provide essential knowledge for the future design of ProGel-Dex that can provide more effective, sustained and safe relief of joint pain and inflammation. Competing Interests: Declaration of competing interest D. Wang, S. R. Goldring, G. Zhao, and X. Wei are co-inventors of a PCT patent application covering ProGel technology. D. Wang and S. R. Goldring hold equity positions in Ensign Pharmaceutical, Inc., a start-up company which has licensed ProGel technology for further preclinical and translational development. The other coauthors declare no competing interest. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Full Text from ScienceDirect