Scientific article
English

Nano wet milled celecoxib extended release microparticles for local management of chronic inflammation

Published inInternational Journal of Pharmaceutics, vol. 589, no. 119783
Publication date2020
Abstract

Osteoarthritis (OA), the most common form of arthritis, is characterized by chronic inflammation, degeneration of articular cartilage and whole joints. Local delivery by intra-articular (IA) injection of small molecules is an established treatment to relieve pain and improve joint motion, requiring month-lasting release of therapeutic drug doses. We incorporated anti-inflammatory drug celecoxib in poly (D, L-lactic acid) microparticles using two spray-drying approaches - either as a solid drug solution or embedded as milled nano drug. Differential scanning calorimetry, X-ray powder diffraction, electron microscopy and in vitro drug release allowed comparison of the microparticles. Both types resulted in spherical particles ranging from 20 to 40 μm mean size, with high drug loadings (10 % to 50 % w/w) and entrapment efficiencies > 80 %. However, after 90 days, in vitro celecoxib release from nano drug embedded microparticles presented a significantly slower release in comparison to drug in solution microparticles, attributed to the presence of stabilized amorphous drug. No cytotoxicity was observed in human articular synoviocytes and PGE2 release was fully suppressed at low doses of both microparticulate systems. This study provides techniques to release high drug loads over months in a tunable manner, providing valuable options for the IA management of osteoarthritis.

Keywords
  • Celecoxib
  • Crystalline behavior
  • Spray dried microparticles
  • Intra-articular injection
  • Drug delivery systems
  • Osteoarthritis
Citation (ISO format)
DE LACERDA SALGADO, Carlota et al. Nano wet milled celecoxib extended release microparticles for local management of chronic inflammation. In: International Journal of Pharmaceutics, 2020, vol. 589, n° 119783. doi: 10.1016/j.ijpharm.2020.119783
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Article (Published version)
accessLevelRestricted
Identifiers
Journal ISSN0378-5173
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Technical informations

Creation10/11/2020 11:06:00
First validation10/11/2020 11:06:00
Update time15/03/2023 23:22:57
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