Omneity® Pellets
All-In-One Vitamin & Mineral Pellet
Sustained intra-articular release of celecoxib from in situ forming gels made of acetyl-capped PCLA-PEG-PCLA triblock copolymers in horses.
Abstract: In this study, the intra-articular tolerability and suitability for local and sustained release of an in situ forming gel composed of an acetyl-capped poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) copolymer loaded with celecoxib was investigated in horse joints. The systems were loaded with two dosages of celecoxib, 50 mg/g ('low CLB gel') and 260 mg/g ('high CLB gel'). Subsequently, they were injected into the joints of five healthy horses. For 72 h after intra-articular injection, they induced a transient inflammatory response, which was also observed after application of Hyonate(®), a commercial formulation containing hyaluronic acid for the intra-articular treatment of synovitis in horses. However, only after administration of the 'high CLB gel' the horses showed signs of discomfort (lameness score: 1.6 ± 1.3 on a 5-point scale) 1 day after injection, which completely disappeared 3 days after injection. Importantly, there was no indication of cartilage damage. Celecoxib Cmax in the joints was reached at 8 h and 24 h after administration of the 'low CLB gel' and 'high CLB gel', respectively. In the joints, concentrations of celecoxib were detected 4 weeks post administration. Celecoxib was also detected in plasma at concentrations of 150 ng/ml at day 3 post administration and thereafter its concentration dropped below the detection limit. These results show that the systems were well tolerated after intra-articular administration and showed local and sustained release of celecoxib for 4 weeks with low and short systemic exposure to the drug, demonstrating that these injectable in situ forming hydrogels are promising vehicles for intra-articular drug delivery.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication Date: 2015-03-18 PubMed ID: 25890740DOI: 10.1016/j.biomaterials.2015.02.109Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research study investigates the use of injectable gels composed of specific polymers, loaded with a medicine called celecoxib, for sustained release of the drug within horse joints. The study findings show that these systems are well-tolerated, and can provide local and sustained release of celecoxib for up to four weeks, with only short and low levels of systemic exposure to the drug.
Methodology and Objectives
- The study aimed at examining intra-articular tolerability and suitability for local and sustained release of a specially formulated gel. The gel comprised of an acetyl-capped poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) copolymer loaded with celecoxib, a non-steroidal anti-inflammatory drug commonly used in arthritis treatment.
- The systems were loaded with two doses of celecoxib – 50 mg/g (referred to as ‘low CLB gel’) and 260 mg/g (‘high CLB gel’).
- The gels were then injected into the joints of five healthy horses, and the outcomes were monitored.
Findings
- Initial response of the horses included a transient (temporary) inflammatory reaction that lasted for three days post-injection, irrespective of the dosage. This reaction can be compared to the response after application of Hyonate®, a commercial formula made of hyaluronic acid used for treating synovitis (inflammation of the joint lining) in horses.
- Horses showed signs of discomfort only following the injection of the ‘high CLB gel’ which manifested as lameness (scoring 1.6 ± 1.3 on a 5-point scale) but disappeared within three days post-injection. Notably, there were no signs of damage to cartilage.
- Celecoxib reached its maximum concentration in the joints at 8 h and 24 h after administration of the ‘low CLB gel’ and ‘high CLB gel’, respectively. Concentrations of the drug were still detected in the joints four weeks after administration.
- In the plasma, the drug was detected at a concentration of 150 ng/ml at day 3 post-administration, beyond which its levels fell below the detection limit.
Conclusion
- The results of this study suggest that the injectable gels show promise as vehicles for intra-articular drug delivery. This is attributed to their good tolerance, ability for localized and sustained release of celecoxib for up to four weeks, and minimal systemic exposure to the drug.
Cite This Article
APA
Petit A, Redout EM, van de Lest CH, de Grauw JC, Müller B, Meyboom R, van Midwoud P, Vermonden T, Hennink WE, René van Weeren P.
(2015).
Sustained intra-articular release of celecoxib from in situ forming gels made of acetyl-capped PCLA-PEG-PCLA triblock copolymers in horses.
Biomaterials, 53, 426-436.
https://doi.org/10.1016/j.biomaterials.2015.02.109 Publication
Researcher Affiliations
- InGell Labs BV, Groningen, The Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
- Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
- Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
- Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
- InGell Labs BV, Groningen, The Netherlands.
- InGell Labs BV, Groningen, The Netherlands.
- InGell Labs BV, Groningen, The Netherlands.
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
- Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. Electronic address: r.vanweeren@uu.nl.
MeSH Terms
- Acetylation
- Animals
- Celecoxib / administration & dosage
- Celecoxib / pharmacokinetics
- Cyclooxygenase 2 Inhibitors / administration & dosage
- Cyclooxygenase 2 Inhibitors / pharmacokinetics
- Drug Carriers
- Gels
- Horses
- Joints / metabolism
- Polyesters / chemistry
- Polyethylene Glycols / chemistry
- Proton Magnetic Resonance Spectroscopy
- Synovial Fluid / metabolism
- X-Ray Diffraction
Citations
This article has been cited 19 times.- Pan P, Simou K, Ouyang Y, Shere L, Preece JA, Jones SW, Davis ET, Lan Y, Chen Z, Zhang ZJ, Li Q. Drug-loaded nanoparticles for intra-articular injection. PLoS One 2026;21(1):e0327958.
- Ali NA, Morsi NM, Badr-Eldin SM, Shamma RN. Diacerein-loaded surface modified iron oxide microparticles (SMIOMPs): an emerging magnetic system for management of osteoarthritis via intra-articular injection. Front Bioeng Biotechnol 2024;12:1439085.
- Weber P, Asadikorayem M, Surman F, Zenobi-Wong M. Zwitterionic polymer-dexamethasone conjugates penetrate and protect cartilage from inflammation. Mater Today Bio 2024 Jun;26:101049.
- Bonato A, Fisch P, Ponta S, Fercher D, Manninen M, Weber D, Eklund KK, Barreto G, Zenobi-Wong M. Engineering Inflammation-Resistant Cartilage: Bridging Gene Therapy and Tissue Engineering. Adv Healthc Mater 2023 Jul;12(17):e2202271.
- Song Y, Day CM, Afinjuomo F, Tan JE, Page SW, Garg S. Advanced Strategies of Drug Delivery via Oral, Topical, and Parenteral Administration Routes: Where Do Equine Medications Stand?. Pharmaceutics 2023 Jan 4;15(1).
- Raina N, Pahwa R, Bhattacharya J, Paul AK, Nissapatorn V, de Lourdes Pereira M, Oliveira SMR, Dolma KG, Rahmatullah M, Wilairatana P, Gupta M. Drug Delivery Strategies and Biomedical Significance of Hydrogels: Translational Considerations. Pharmaceutics 2022 Mar 5;14(3).
- Carvalho JRG, Conde G, Antonioli ML, Santana CH, Littiere TO, Dias PP, Chinelatto MA, Canola PA, Zara FJ, Ferraz GC. Long-Term Evaluation of Poly(lactic acid) (PLA) Implants in a Horse: An Experimental Pilot Study. Molecules 2021 Nov 29;26(23).
- Klimak M, Nims RJ, Pferdehirt L, Collins KH, Harasymowicz NS, Oswald SJ, Setton LA, Guilak F. Immunoengineering the next generation of arthritis therapies. Acta Biomater 2021 Oct 1;133:74-86.
- Salgado C, Jordan O, Allémann E. Osteoarthritis In Vitro Models: Applications and Implications in Development of Intra-Articular Drug Delivery Systems. Pharmaceutics 2021 Jan 5;13(1).
- Nishida Y, Kano K, Nobuoka Y, Seo T. Sustained-release diclofenac conjugated to hyaluronate (diclofenac etalhyaluronate) for knee osteoarthritis: a randomized phase 2 study. Rheumatology (Oxford) 2021 Mar 2;60(3):1435-1444.
- Mancipe Castro LM, García AJ, Guldberg RE. Biomaterial strategies for improved intra-articular drug delivery. J Biomed Mater Res A 2021 Apr;109(4):426-436.
- Kasiński A, Zielińska-Pisklak M, Oledzka E, Sobczak M. Smart Hydrogels - Synthetic Stimuli-Responsive Antitumor Drug Release Systems. Int J Nanomedicine 2020;15:4541-4572.
- Küçüktürkmen B, Öz UC, Bozkir A. In Situ Hydrogel Formulation for Intra-Articular Application of Diclofenac Sodium-Loaded Polymeric Nanoparticles. Turk J Pharm Sci 2017 Apr;14(1):56-64.
- Hoang Thi TT, Sinh LH, Huynh DP, Nguyen DH, Huynh C. Self-Assemblable Polymer Smart-Blocks for Temperature-Induced Injectable Hydrogel in Biomedical Applications. Front Chem 2020;8:19.
- Koh RH, Jin Y, Kim J, Hwang NS. Inflammation-Modulating Hydrogels for Osteoarthritis Cartilage Tissue Engineering. Cells 2020 Feb 12;9(2).
- Tellegen AR, Rudnik-Jansen I, Pouran B, de Visser HM, Weinans HH, Thomas RE, Kik MJL, Grinwis GCM, Thies JC, Woike N, Mihov G, Emans PJ, Meij BP, Creemers LB, Tryfonidou MA. Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis. Drug Deliv 2018 Nov;25(1):1438-1447.
- Bajpayee AG, De la Vega RE, Scheu M, Varady NH, Yannatos IA, Brown LA, Krishnan Y, Fitzsimons TJ, Bhattacharya P, Frank EH, Grodzinsky AJ, Porter RM. Sustained intra-cartilage delivery of low dose dexamethasone using a cationic carrier for treatment of post traumatic osteoarthritis. Eur Cell Mater 2017 Dec 5;34:341-364.
- Bajpayee AG, Grodzinsky AJ. Cartilage-targeting drug delivery: can electrostatic interactions help?. Nat Rev Rheumatol 2017 Mar;13(3):183-193.
- Huang Q, Cheng GP, Chiu K, Wang GQ. Surface Modification of Intraocular Lenses. Chin Med J (Engl) 2016 Jan 20;129(2):206-14.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
