A novel diclofenac-hydrogel conjugate system for intraarticular sustained release: Development of 2-pyridylamino-substituted 1-phenylethanol (PAPE) and its derivatives as tunable traceless linkers

[Display omitted] A local sustained-release drug delivery system, or depot, for intra-articular injection offers the opportunity to release a therapeutic agent directly to the joint with limited need for reinjection. A successful system would provide more consistent efficacy and minimize systemic si...

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Bibliographic Details
Published in:International journal of pharmaceutics 2020-07, Vol.585, p.119519-119519, Article 119519
Main Authors: Kawanami, Toshio, LaBonte, Laura R., Amin, Jakal, Thibodeaux, Stefan J., Lee, Cameron C., Argintaru, O. Andreea, Adams, Christopher M.
Format: Article
Language:English
Subjects:
2-Pyridylamino substituted 1-phenylethanol (PAPE)
Animals
Anti-Inflammatory Agents, Non-Steroidal - administration & dosage
Benzyl Alcohols - chemistry
Cattle
Chemistry, Pharmaceutical - methods
Delayed-Action Preparations
Diclofenac
Diclofenac - administration & dosage
Drug delivery system
Drug Delivery Systems - methods
Humans
Hydrogel
Hydrogels - chemistry
Hydrogen-Ion Concentration
Injections, Intra-Articular
Osteoarthritis
Polymeric prodrug
Prodrugs
Sustained release
Synovial Fluid
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Summary:[Display omitted] A local sustained-release drug delivery system, or depot, for intra-articular injection offers the opportunity to release a therapeutic agent directly to the joint with limited need for reinjection. A successful system would provide more consistent efficacy and minimize systemic side effects. In this paper, we explore the potential use of diclofenac, a non-steroidal anti-inflammatory drug, for use in a polymer-conjugate depot system. During the course of our exploration it was determined that “conventional ester” conjugates of diclofenac were not appropriate as upon incubation in buffer (pH 7.4) or in bovine synovial fluid, a considerable amount of undesired diclofenac-lactam was released. Thus we developed a novel linker system for diclofenac in order to minimize the production of the lactam. This new linker enables a diclofenac conjugate system with tunable release rates and minimizes the production of undesired lactam side-products.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2020.119519