Intra-Articular Slow-Release Triamcinolone Acetonide from Polyesteramide Microspheres as a Treatment for Osteoarthritis.

Jens Thies,Imke Rudnik-Jansen,George Mihov,Laura Creemers,Anna Tellegen,Nicolien van Klaveren,Nina Woike,Martijn Beukers,Erik Teske,Björn Meij,Marianna Tryfonidou,Kan Loi How

doi:10.3390/pharmaceutics13030372

Jens Thies, Imke Rudnik-Jansen + Show 10 more

Open Access

https://doi.org/10.3390/pharmaceutics13030372

Copy DOI

Abstract

Osteoarthritis (OA) is a common cause of pain and disability. Local corticosteroid injections are effective in treating OA pain and inflammation but are short-acting. Prolonged intra-articular (IA) corticosteroid exposure may even lead to cartilage deterioration. The aim of this prospective study was to assess safety and provide proof-of-concept of IA-applied biodegradable polyesteramide-based microspheres (PEAMs) gradually releasing triamcinolone acetonide (TA). Mimicking continuous exposure associated with local drug delivery in canine articular chondrocytes cultured in the continuous presence of TA tissue regeneration was not affected, whereas intermittent exposure reduced proteoglycan production. In this respect, TA-PEAMs administered IA in a proof-of-concept study in 12 client-owned dogs with established OA also showed safety by radiographic examination, without changes in OA severity and in glycosaminoglycan synovial fluid levels. Treatment also resulted in clinical improvement in 10 out of 11 dogs during the two-month follow-up period, which persisted in 6 out of 10 dogs after 6 months, based on objective gait analysis and owner questionnaires. Synovial prostaglandin E2, a pro-inflammatory marker, was decreased two months after treatment. This study showed safety and proof-of-concept of IA-administered TA-PEAMs in dogs with OA, as a first step towards translation into the veterinary and human clinic.

Highlights

The microspheres used in the current study have been used and characterized in another study published recently [25]
The peak vertiacetonide-loaded microspheres. (a) The symmetry index (SI) of the peak vertical force (a) wasofimproved at one and two cal force (a) was improved at one and two months post injection (p = 0.04, p = 0.027) compared to months post injection (p = 0.04, p = 0.027) compared to baseline. (b) The peak propulsive force was improved at the baseline. (b) The peak propulsive force was improved at the one-month follow-up (p = 0.041). (c) one-month follow-up (p = 0.041). (c) There was a borderline significant decrease in vertical impulse SI at one and two
Thevisual visuallameness lameness score compared to to baseline during the entire baseline study period

Summary

Introduction

Osteoarthritis (OA) is a debilitating and chronic disease, leading to loss of quality of life and decreased productivity, which in turn leads to increased socioeconomic costs. With the increase in life expectancy, its prevalence is expected to rise [1]. Pain, swelling and stiffness of the affected joint are the main clinical signs of OA [2]. OA is characterized by degeneration of articular cartilage, accompanied by pathological changes in subchondral bone and the synovial lining, such as osteophyte formation and synovial inflammation. Among others mediated by the pro-inflammatory cytokine prostaglandin

Objectives

Methods

Results

Conclusion