Dry powder aerosol containing muco-inert particles for excipient enhanced growth pulmonary drug delivery

Guihong Chai; Amr Hassan; Tuo Meng; Lihua Lou; Jonathan Ma; Russell Simmers; Lei Zhou; Bruce K Rubin; Qi Tony Zhou; P Worth Longest; Michael Hindle; Qingguo Xu

doi:10.1016/j.nano.2020.102262

Dry powder aerosol containing muco-inert particles for excipient enhanced growth pulmonary drug delivery

Nanomedicine. 2020 Oct:29:102262. doi: 10.1016/j.nano.2020.102262. Epub 2020 Jul 3.

Authors

Guihong Chai¹, Amr Hassan¹, Tuo Meng¹, Lihua Lou¹, Jonathan Ma², Russell Simmers³, Lei Zhou⁴, Bruce K Rubin², Qi Tony Zhou⁵, P Worth Longest⁶, Michael Hindle¹, Qingguo Xu⁷

Affiliations

¹ Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA.
² Department of Pediatrics, Children's Hospital of Richmond, Virginia Commonwealth University, Richmond, VA, USA.
³ Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA; Department of Physics, College of Humanities & Sciences, Virginia Commonwealth University, Richmond, VA, USA.
⁴ Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA, USA.
⁵ Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN, USA.
⁶ Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA; Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, VA, USA.
⁷ Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA; Department of Ophthalmology, Massey Cancer Center, Center for Pharmaceutical Engineering, and Institute for Structural Biology, Drug Discovery & Development (ISB3D), Virginia Commonwealth University, Richmond, VA, USA. Electronic address: qxu@vcu.edu.

Abstract

Tenacious sputum poses a critical diffusion barrier for aerosol antibiotics used to treat cystic fibrosis (CF) lung infection. We conducted a proof-of-concept study using dense poly(ethylene glycol) coated polystyrene nanoparticles (PS-PEG NPs) as model muco-inert particles (MIPs) formulated as a powder using an excipient enhanced growth (EEG) strategy, aiming to minimize extrathoracic airway loss, maximize deposition in the airway and further overcome the sputum barrier in the CF lungs. The EEG aerosol formulation containing PS-PEG MIPs was prepared by spray drying and produced discrete spherical particles with geometric diameter of approximately 2 μm; and >80% of the powder dose was delivered from a new small-animal dry powder inhaler (DPI). The MIPs released from the EEG aerosol had human airway mucus and CF sputum diffusion properties comparable to the suspension formulation. These properties make this formulation a promising pulmonary drug delivery system for CF lung infections.

Keywords: CF sputum; Dry powder inhaler; Mucus penetration; Multiple particle tracking; Spray drying.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Administration, Inhalation
Cystic Fibrosis / drug therapy*
Cystic Fibrosis / pathology
Drug Delivery Systems*
Dry Powder Inhalers / methods
Excipients / chemistry
Humans
Lung / drug effects*
Lung / growth & development
Lung Diseases / drug therapy*
Lung Diseases / pathology
Mucus / drug effects
Nanoparticles / chemistry*
Polyethylene Glycols / chemistry
Polyethylene Glycols / pharmacology
Polystyrenes / chemistry
Polystyrenes / pharmacology

Substances

Excipients
Polystyrenes
Polyethylene Glycols

Abstract

Publication types

MeSH terms

Substances

Grants and funding