Identification of Formulation Parameters That Affect the Analgesic Efficacy of ProGel-Dex - A Thermoresponsive Polymeric Dexamethasone Prodrug for Chronic Arthritis Pain Relief

Overview

Journal Nanomedicine

Publisher Elsevier

Specialties Biomedical Engineering
Biotechnology

Date 2024 Aug 23

PMID 39179013

Authors

Xin Wei

Gang Zhao

Ningrong Chen

Xiaoke Xu

Haochen Jiang

Daniel Tran

Evan Glissmeyer

Mary B Goldring

Steven R Goldring

Dong Wang

Affiliations

Soon will be listed here.

Abstract

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.

References

Glyn-Jones S, Palmer A, Agricola R, Price A, Vincent T, Weinans H . Osteoarthritis. Lancet. 2015; 386(9991):376-87. DOI: 10.1016/S0140-6736(14)60802-3. View

Bannuru R, Osani M, Vaysbrot E, Arden N, Bennell K, Bierma-Zeinstra S . OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019; 27(11):1578-1589. DOI: 10.1016/j.joca.2019.06.011. View

Bodick N, Lufkin J, Willwerth C, Kumar A, Bolognese J, Schoonmaker C . An intra-articular, extended-release formulation of triamcinolone acetonide prolongs and amplifies analgesic effect in patients with osteoarthritis of the knee: a randomized clinical trial. J Bone Joint Surg Am. 2015; 97(11):877-88. DOI: 10.2106/JBJS.N.00918. View

Latourte A, Rat A, Omorou A, Ngueyon-Sime W, Eymard F, Sellam J . Do Glucocorticoid Injections Increase the Risk of Knee Osteoarthritis Progression Over 5 Years?. Arthritis Rheumatol. 2022; 74(8):1343-1351. DOI: 10.1002/art.42118. View

Buelt A, Narducci D . Osteoarthritis Management: Updated Guidelines from the American College of Rheumatology and Arthritis Foundation. Am Fam Physician. 2021; 103(2):120-121. View

Horvath S, HOLLANDER J . INTRA-ARTICULAR TEMPERATURE AS A MEASURE OF JOINT REACTION. J Clin Invest. 1949; 28(3):469-73. PMC: 439623. DOI: 10.1172/JCI102092. View

Paik J, Duggan S, Keam S . Triamcinolone Acetonide Extended-Release: A Review in Osteoarthritis Pain of the Knee. Drugs. 2019; 79(4):455-462. PMC: 6437125. DOI: 10.1007/s40265-019-01083-3. View

Samuels J, Pillinger M, Jevsevar D, Felson D, Simon L . Critical appraisal of intra-articular glucocorticoid injections for symptomatic osteoarthritis of the knee. Osteoarthritis Cartilage. 2020; 29(1):8-16. DOI: 10.1016/j.joca.2020.09.001. View

Arden N, Perry T, Bannuru R, Bruyere O, Cooper C, Haugen I . Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nat Rev Rheumatol. 2020; 17(1):59-66. DOI: 10.1038/s41584-020-00523-9. View

10.

Liu X, Quan L, Tian J, Alnouti Y, Fu K, Thiele G . Synthesis and evaluation of a well-defined HPMA copolymer-dexamethasone conjugate for effective treatment of rheumatoid arthritis. Pharm Res. 2008; 25(12):2910-9. PMC: 2593120. DOI: 10.1007/s11095-008-9683-3. View

11.

Chen N, Wei X, Zhao G, Jia Z, Fu X, Jiang H . Single dose thermoresponsive dexamethasone prodrug completely mitigates joint pain for 15 weeks in a murine model of osteoarthritis. Nanomedicine. 2024; 57:102735. PMC: 11229676. DOI: 10.1016/j.nano.2024.102735. View

12.

Felson D . Evidence suggests that intraarticular corticosteroids are effective (short term) and safe (long term). Osteoarthritis Cartilage. 2022; 31(2):140-141. PMC: 9892243. DOI: 10.1016/j.joca.2022.10.010. View

13.

Zhao G, Ren R, Wei X, Jia Z, Chen N, Sun Y . Thermoresponsive polymeric dexamethasone prodrug for arthritis pain. J Control Release. 2021; 339:484-497. PMC: 8599655. DOI: 10.1016/j.jconrel.2021.10.007. View

14.

Hunter D, McDougall J, Keefe F . The symptoms of osteoarthritis and the genesis of pain. Rheum Dis Clin North Am. 2008; 34(3):623-43. PMC: 2597216. DOI: 10.1016/j.rdc.2008.05.004. View

15.

Bucci J, Chen X, LaValley M, Nevitt M, Torner J, Lewis C . Progression of Knee Osteoarthritis With Use of Intraarticular Glucocorticoids Versus Hyaluronic Acid. Arthritis Rheumatol. 2021; 74(2):223-226. PMC: 8795477. DOI: 10.1002/art.42031. View

16.

Blankstein M, Lentine B, Nelms N . Common Practices in Intra-Articular Corticosteroid Injection for the Treatment of Knee Osteoarthritis: A Survey of the American Association of Hip and Knee Surgeons Membership. J Arthroplasty. 2021; 36(3):845-850. DOI: 10.1016/j.arth.2020.09.022. View

17.

Conaghan P, Cohen S, Berenbaum F, Lufkin J, Johnson J, Bodick N . Brief Report: A Phase IIb Trial of a Novel Extended-Release Microsphere Formulation of Triamcinolone Acetonide for Intraarticular Injection in Knee Osteoarthritis. Arthritis Rheumatol. 2017; 70(2):204-211. PMC: 5814922. DOI: 10.1002/art.40364. View

18.

Waung J, Bassett J, Williams G . Adult mice lacking the type 2 iodothyronine deiodinase have increased subchondral bone but normal articular cartilage. Thyroid. 2014; 25(3):269-77. PMC: 4361410. DOI: 10.1089/thy.2014.0476. View

19.

Itoh H, Suzuta T, Hoshino T, Takaya N . Novel dehydrogenase catalyzes oxidative hydrolysis of carbon-nitrogen double bonds for hydrazone degradation. J Biol Chem. 2007; 283(9):5790-800. DOI: 10.1074/jbc.M709027200. View

20.

Robinson W, Lepus C, Wang Q, Raghu H, Mao R, Lindstrom T . Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016; 12(10):580-92. PMC: 5500215. DOI: 10.1038/nrrheum.2016.136. View