Applicability of a Modified Rat Model of Acute Arthritis for Long-Term Testing of Drug Delivery Systems

Imke Rudnik-Jansen; Nina Woike; Suzanne de Jong; Sabine Versteeg; Marja Kik; Pieter Emans; George Mihov; Jens Thies; Niels Eijkelkamp; Marianna Tryfonidou; Laura Creemers

doi:10.3390/pharmaceutics11020070

Applicability of a Modified Rat Model of Acute Arthritis for Long-Term Testing of Drug Delivery Systems

Imke Rudnik-Jansen, Nina Woike, Suzanne de Jong, Sabine Versteeg, Marja Kik, Pieter Emans, George Mihov, Jens Thies, Niels Eijkelkamp, Marianna Tryfonidou, Laura Creemers^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Episodes of inflammation and pain are predominant features of arthritic joint diseases. Drug delivery systems (DDS) could reduce inflammation and pain long-term without chances of infection upon multiple injections. To allow for long-term evaluation of DDS, we modified a previously published acute arthritis model by extending follow-up periods between flare-ups. Unilateral synovial inflammation of the knee was induced by intra-articular injection of streptococcal cell wall peptidoglycan polysaccharide (PGPS), and flare-ups were induced by intravenous PGPS injections every 4 weeks for a total duration of 84 days. In PGPS-reactivated animals, joint swelling, pain behavior, post mortem synovitis, and osteophyte formation were notable features. Hepatitis, splenitis and inflammation of non-primed joints were observed as systemic side effects. To test the applicability of the modified arthritis model for long-term testing of DDS, the duration of anti-inflammatory and analgesic effects of a corticosteroid released from two different polymer-based platforms was evaluated. The current modified arthritis model has good applicability for testing of DDS for a prolonged period of time. Furthermore, the novel autoregulatory polyesteramide (PEA) microsphere platform releasing triamcinolone acetonide (TAA) was benchmarked against poly lactic-co-glycolic acid (PLGA) and reduced joint swelling and pain behavior more potently compared to TAA-loaded PLGA microspheres.

Original language	English
Article number	70
Number of pages	17
Journal	Pharmaceutics
Volume	11
Issue number	2
DOIs	https://doi.org/10.3390/pharmaceutics11020070
Publication status	Published - Feb 2019

Keywords

drug delivery systems
inflammation
arthritis
pain
polyester amide
poly lactic-co-glycolic acid
TRIAMCINOLONE ACETONIDE
RHEUMATOID-ARTHRITIS
POLY(ESTER AMIDE)S
OSTEOARTHRITIS
BIODEGRADATION
INFLAMMATION
CELECOXIB
RELEASE
MICROSPHERES
FORMULATION

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@article{4323ad684e95467b917584d36a273f4e,

title = "Applicability of a Modified Rat Model of Acute Arthritis for Long-Term Testing of Drug Delivery Systems",

abstract = "Episodes of inflammation and pain are predominant features of arthritic joint diseases. Drug delivery systems (DDS) could reduce inflammation and pain long-term without chances of infection upon multiple injections. To allow for long-term evaluation of DDS, we modified a previously published acute arthritis model by extending follow-up periods between flare-ups. Unilateral synovial inflammation of the knee was induced by intra-articular injection of streptococcal cell wall peptidoglycan polysaccharide (PGPS), and flare-ups were induced by intravenous PGPS injections every 4 weeks for a total duration of 84 days. In PGPS-reactivated animals, joint swelling, pain behavior, post mortem synovitis, and osteophyte formation were notable features. Hepatitis, splenitis and inflammation of non-primed joints were observed as systemic side effects. To test the applicability of the modified arthritis model for long-term testing of DDS, the duration of anti-inflammatory and analgesic effects of a corticosteroid released from two different polymer-based platforms was evaluated. The current modified arthritis model has good applicability for testing of DDS for a prolonged period of time. Furthermore, the novel autoregulatory polyesteramide (PEA) microsphere platform releasing triamcinolone acetonide (TAA) was benchmarked against poly lactic-co-glycolic acid (PLGA) and reduced joint swelling and pain behavior more potently compared to TAA-loaded PLGA microspheres.",

keywords = "drug delivery systems, inflammation, arthritis, pain, polyester amide, poly lactic-co-glycolic acid, TRIAMCINOLONE ACETONIDE, RHEUMATOID-ARTHRITIS, POLY(ESTER AMIDE)S, OSTEOARTHRITIS, BIODEGRADATION, INFLAMMATION, CELECOXIB, RELEASE, MICROSPHERES, FORMULATION",

author = "Imke Rudnik-Jansen and Nina Woike and {de Jong}, Suzanne and Sabine Versteeg and Marja Kik and Pieter Emans and George Mihov and Jens Thies and Niels Eijkelkamp and Marianna Tryfonidou and Laura Creemers",

note = "Funding Information: Conflicts of Interest: The project is a public private partnership funded by Health Holland, (contract #40-43100-98-022), with DSM Biomedical B.V. as partner. Nina Woike, George Mihov and Jens Thies are DSM employees and have proprietary and commercial interest in material discussed in this article. They produced the loaded microspheres and provided the in vitro release data. They had no role in the design of the study, collection, analysis or interpretation of the in vivo data, writing the manuscript, nor in the decision to publish the data. Part of the contractual agreement is a delay for disclosure up to a maximum of 45 days after receipt of the manuscript version. All other authors have nothing to disclose. Funding Information: Funding: This work was financially supported by a research grant from Life Sciences Health (LSH) Impulse, (ArIADNE; project #40-43100-98-022). Also the financial contribution of the Dutch Arthritis Foundation is gratefully acknowledged (LLP22 and LLP12). Publisher Copyright: {\textcopyright} 2019 by the author.",

year = "2019",

month = feb,

doi = "10.3390/pharmaceutics11020070",

language = "English",

volume = "11",

journal = "Pharmaceutics",

issn = "1999-4923",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "2",

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T1 - Applicability of a Modified Rat Model of Acute Arthritis for Long-Term Testing of Drug Delivery Systems

AU - Rudnik-Jansen, Imke

AU - Woike, Nina

AU - de Jong, Suzanne

AU - Versteeg, Sabine

AU - Kik, Marja

AU - Emans, Pieter

AU - Mihov, George

AU - Thies, Jens

AU - Eijkelkamp, Niels

AU - Tryfonidou, Marianna

AU - Creemers, Laura

N1 - Funding Information: Conflicts of Interest: The project is a public private partnership funded by Health Holland, (contract #40-43100-98-022), with DSM Biomedical B.V. as partner. Nina Woike, George Mihov and Jens Thies are DSM employees and have proprietary and commercial interest in material discussed in this article. They produced the loaded microspheres and provided the in vitro release data. They had no role in the design of the study, collection, analysis or interpretation of the in vivo data, writing the manuscript, nor in the decision to publish the data. Part of the contractual agreement is a delay for disclosure up to a maximum of 45 days after receipt of the manuscript version. All other authors have nothing to disclose. Funding Information: Funding: This work was financially supported by a research grant from Life Sciences Health (LSH) Impulse, (ArIADNE; project #40-43100-98-022). Also the financial contribution of the Dutch Arthritis Foundation is gratefully acknowledged (LLP22 and LLP12). Publisher Copyright: © 2019 by the author.

PY - 2019/2

Y1 - 2019/2

N2 - Episodes of inflammation and pain are predominant features of arthritic joint diseases. Drug delivery systems (DDS) could reduce inflammation and pain long-term without chances of infection upon multiple injections. To allow for long-term evaluation of DDS, we modified a previously published acute arthritis model by extending follow-up periods between flare-ups. Unilateral synovial inflammation of the knee was induced by intra-articular injection of streptococcal cell wall peptidoglycan polysaccharide (PGPS), and flare-ups were induced by intravenous PGPS injections every 4 weeks for a total duration of 84 days. In PGPS-reactivated animals, joint swelling, pain behavior, post mortem synovitis, and osteophyte formation were notable features. Hepatitis, splenitis and inflammation of non-primed joints were observed as systemic side effects. To test the applicability of the modified arthritis model for long-term testing of DDS, the duration of anti-inflammatory and analgesic effects of a corticosteroid released from two different polymer-based platforms was evaluated. The current modified arthritis model has good applicability for testing of DDS for a prolonged period of time. Furthermore, the novel autoregulatory polyesteramide (PEA) microsphere platform releasing triamcinolone acetonide (TAA) was benchmarked against poly lactic-co-glycolic acid (PLGA) and reduced joint swelling and pain behavior more potently compared to TAA-loaded PLGA microspheres.

AB - Episodes of inflammation and pain are predominant features of arthritic joint diseases. Drug delivery systems (DDS) could reduce inflammation and pain long-term without chances of infection upon multiple injections. To allow for long-term evaluation of DDS, we modified a previously published acute arthritis model by extending follow-up periods between flare-ups. Unilateral synovial inflammation of the knee was induced by intra-articular injection of streptococcal cell wall peptidoglycan polysaccharide (PGPS), and flare-ups were induced by intravenous PGPS injections every 4 weeks for a total duration of 84 days. In PGPS-reactivated animals, joint swelling, pain behavior, post mortem synovitis, and osteophyte formation were notable features. Hepatitis, splenitis and inflammation of non-primed joints were observed as systemic side effects. To test the applicability of the modified arthritis model for long-term testing of DDS, the duration of anti-inflammatory and analgesic effects of a corticosteroid released from two different polymer-based platforms was evaluated. The current modified arthritis model has good applicability for testing of DDS for a prolonged period of time. Furthermore, the novel autoregulatory polyesteramide (PEA) microsphere platform releasing triamcinolone acetonide (TAA) was benchmarked against poly lactic-co-glycolic acid (PLGA) and reduced joint swelling and pain behavior more potently compared to TAA-loaded PLGA microspheres.

KW - drug delivery systems

KW - inflammation

KW - arthritis

KW - pain

KW - polyester amide

KW - poly lactic-co-glycolic acid

KW - TRIAMCINOLONE ACETONIDE

KW - RHEUMATOID-ARTHRITIS

KW - POLY(ESTER AMIDE)S

KW - OSTEOARTHRITIS

KW - BIODEGRADATION

KW - INFLAMMATION

KW - CELECOXIB

KW - RELEASE

KW - MICROSPHERES

KW - FORMULATION

U2 - 10.3390/pharmaceutics11020070

DO - 10.3390/pharmaceutics11020070

M3 - Article

C2 - 30736430

SN - 1999-4923

VL - 11

JO - Pharmaceutics

JF - Pharmaceutics

IS - 2

M1 - 70

ER -

Applicability of a Modified Rat Model of Acute Arthritis for Long-Term Testing of Drug Delivery Systems

Abstract

Keywords

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