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.
Pharm Res
; 32(2): 680-90, 2015 Feb.
Article
en En
| MEDLINE
| ID: mdl-25163981
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 (PGE2) 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 PGE2 production was determined over a period of 21 days.RESULTS:
PLGA(7525)-PTE microspheres were prepared and loaded with CXB and TA at 86 and 97% loading efficiency, respectively. In the bioactivity assay, PGE2 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, PGE2 production was initially reduced to 3% and gradually recovered to 30% reduction. At 1 nmol loading, PGE2 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Ácido Poliglicólico
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Pirazoles
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Sulfonamidas
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Triamcinolona Acetonida
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Portadores de Fármacos
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Ácido Láctico
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Microesferas
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Antiinflamatorios
Límite:
Humans
Idioma:
En
Revista:
Pharm Res
Año:
2015
Tipo del documento:
Article
País de afiliación:
Países Bajos