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- Title
Applicability of a Newly Developed Bioassay for Determining Bioactivity of Anti-Inflammatory Compounds in Release Studies − Celecoxib and Triamcinolone Acetonide Released from Novel PLGA-Based Microspheres.
- Authors
Yang, Hsiao-yin; Dijk, Maarten; Licht, Ruud; Beekhuizen, Michiel; Rijen, Mattie; Janstål, Martina; Öner, F.; Dhert, Wouter; Schumann, Detlef; Creemers, Laura
- Abstract
Purpose: : To develop a bio-assay for measuring long-term bioactivity of released anti-inflammatory compounds and to test the bioactivity of celecoxib (CXB) and triamcinolone acetonide (TA) released from a new PLGA-based microsphere platform. Methods: : Human osteoarthritic chondrocytes were plated according to standardized procedures after batch-wise harvest and cultured for 3 days to prevent cell confluency and changes in cell behaviour. Prostaglandin E2 (PGE) production stimulated by TNFα was used as a parameter of inflammation. A novel microsphere platform based on PTE-functionalised PLGA was used to incorporate CXB and TA. Loaded microspheres were added to transwells overlying the cells, with transfer of the wells to new cell cultures every 3 days. Inhibition of PGE production was determined over a period of 21 days. Results: : PLGA(75:25)-PTE microspheres were prepared and loaded with CXB and TA at 86 and 97% loading efficiency, respectively. In the bioactivity assay, PGE levels induced by TNFα were reduced to an average of 30% using microspheres loaded with 0.1 nmol CXB per transwell; with microspheres loaded with 0.1 nmol TA, PGE production was initially reduced to 3% and gradually recovered to 30% reduction. At 1 nmol loading, PGE was inhibited to 0-7% for CXB-loaded microspheres, and 0-28% for TA-loaded microspheres. Conclusions: : We present a novel sustained release bioactivity assay which provides an essential link between in vitro buffer-based release kinetics and in vivo application. Novel PLGA-based microspheres loaded with TA and CXB showed efficient anti-inflammatory effects over time.
- Subjects
DRUG development; BIOLOGICAL assay; CONTROLLED release drugs; ANTI-infective agents; CELECOXIB; TRIAMCINOLONE acetonide; DINOPROSTONE
- Publication
Pharmaceutical Research, 2015, Vol 32, Issue 2, p680
- ISSN
0724-8741
- Publication type
Article
- DOI
10.1007/s11095-014-1495-z