Respiratory Administration of Infliximab Dry Powder for Local Suppression of Inflammation
Autor: | Hamed Montazeri, Homa Faghihi, Abdolhossein Rouholamini Najafabadi, Zahra Daman, Alireza Vatanara, Elham Ghasemian |
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Rok vydání: | 2019 |
Předmět: |
Light
Ovalbumin Anti-Inflammatory Agents Pharmaceutical Science 02 engineering and technology Aquatic Science 030226 pharmacology & pharmacy Excipients Mice 03 medical and health sciences 0302 clinical medicine Drug Stability In vivo Administration Inhalation Spectroscopy Fourier Transform Infrared Drug Discovery Animals Scattering Radiation Particle Size Respiratory system Lung Ecology Evolution Behavior and Systematics Aerosolization EC50 Mice Inbred BALB C Chromatography Ecology biology Inhalation Tumor Necrosis Factor-alpha Chemistry Dry Powder Inhalers General Medicine 021001 nanoscience & nanotechnology Infliximab Spray drying Chromatography Gel Microscopy Electron Scanning biology.protein Particle size 0210 nano-technology Agronomy and Crop Science |
Zdroj: | AAPS PharmSciTech. 20 |
ISSN: | 1530-9932 |
Popis: | 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. EC50 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. |
Databáze: | OpenAIRE |
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