AAPS PharmSciTech

, 20:128 | Cite as

Respiratory Administration of Infliximab Dry Powder for Local Suppression of Inflammation

  • Homa Faghihi
  • Abdolhossein Rouholamini Najafabadi
  • Zahra Daman
  • Elham Ghasemian
  • Hamed Montazeri
  • Alireza VatanaraEmail author
Research Article


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.


infliximab spray drying inflammation respiratory delivery bioactivity 







Tumor necrosis factor alpha


Monoclonal antibody


Interleukin 5


Airway hyperresponsiveness


Metered dose inhalers


Dry powder inhalers


Immunoglobulin G


Intravenous immunoglobulin


Size exclusion high pressure liquid chromatography


Sodium dodecyl sulfate polyacrylamide gel electrophoresis


Fourier transform infrared


Scanning electron microscopy


Methyl tetrazolium


Roswell Park Memorial Institute


American Type Culture Collection


Potassium bromide


Twin stage impinger


Emitted dose


Fine particle dose


Fine particle fraction


Anti-drug antibody


Supplementary material

12249_2019_1308_MOESM1_ESM.docx (147 kb)
ESM 1 (DOCX 146 kb)
12249_2019_1308_MOESM2_ESM.docx (59 kb)
ESM 2 (DOCX 58 kb)
12249_2019_1308_MOESM3_ESM.docx (33 kb)
ESM 3 (DOCX 33 kb)
12249_2019_1308_Fig7_ESM.png (227 kb)
Fig. 1A

supplement SEC-HPLC chromatogram of F1 (PNG 226 kb)

12249_2019_1308_MOESM4_ESM.tif (91 kb)
High Resolution Image (TIF 91 kb)
12249_2019_1308_Fig8_ESM.png (217 kb)
Fig. 1B

supplement SEC-HPLC chromatogram of F9 (PNG 217 kb)

12249_2019_1308_MOESM5_ESM.tif (93 kb)
High Resolution Image (TIF 93 kb)
12249_2019_1308_Fig9_ESM.png (230 kb)
Fig. 1C

supplement SEC-HPLC chromatogram of Remicade (PNG 229 kb)

12249_2019_1308_MOESM6_ESM.tif (98 kb)
High Resolution Image (TIF 97 kb)
12249_2019_1308_Fig10_ESM.png (176 kb)
Fig. 2

supplement (PNG 175 kb)

12249_2019_1308_MOESM7_ESM.tif (71 kb)
High Resolution Image (TIF 70 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Homa Faghihi
    • 1
  • Abdolhossein Rouholamini Najafabadi
    • 1
  • Zahra Daman
    • 1
  • Elham Ghasemian
    • 1
  • Hamed Montazeri
    • 2
  • Alireza Vatanara
    • 1
    • 3
    Email author
  1. 1.Department of Pharmaceutics, Faculty of PharmacyTehran University of Medical SciencesTehranIran
  2. 2.School of Pharmacy-International CampusIran University of Medical SciencesTehranIran
  3. 3.Aerosol Research Laboratory, Department of Pharmaceutics, School of PharmacyTehran University of Medical SciencesTehranIran

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