Respiratory Administration of Infliximab Dry Powder for Local Suppression of Inflammation

AAPS PharmSciTech(2019)

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摘要
The airways are verified as a relevant route to improve antibody therapeutic index with superior lung concentration but limited passage into systemic blood stream. The current research aimed to process spray-dried (SD) powder of Infliximab to assess the feasibility of respiratory delivery of antibody for local suppression of lung-secreted tumor necrosis factor α (TNFα). Molecular and structural stability of powders were determined through size exclusion chromatography (SEC-HPLC) and Fourier transform infrared (FTIR) spectroscopy. Particle properties were characterized by laser light scattering, twin stage impinger (TSI), and scanning electron microscopy (SEM). In vitro biological activity was quantified applying L-929 cell line. Ovalbumin (OVA)-challenged balb/c mice were employed to evaluate the anti-TNFα activity of antibody formulation as in vivo experimental model. SD sample consisting of 36 mg trehalose, 12 mg cysteine, and 0.05% of Tween 20 was selected with minimum aggregation/fragmentation rate constants of 0.07 and 0.05 (1/month) based on 1 and 2 months of storage at 40°C and relative humidity of 75%. Fine particle fraction (FPF) value of this formulation was 67.75% with desired particle size and surface morphology for respiratory delivery. EC 50 was 8.176 and 6.733 ng/ml for SD Infliximab and Remicade®, respectively. SD antibody reduced TNFα (26.56 pg/ml) secretion in mouse lung tissue, more than 2 orders of magnitudes comparing positive control group (TNFα, 68.34 pg/ml). The success of antibody inhalation mainly depended on the spray drying condition, formulation components, and stability of antibody within aerosolization. Inhaled Infliximab could be a potential drug for local inhibition of lung inflammation.
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关键词
infliximab,spray drying,inflammation,respiratory delivery,bioactivity
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