Novel inhalation formulation to improve quality of life of cystic fibrosis sufferers

Summary

The proposed research project aims to devise a novel dual-action aerosol formulation to be delivered directly to the site of the disease and that could be efficacious on both the major symptoms presents in cystic fibrosis patients: the build up of thick mucus and the bacterial inflammation.

Supervisor(s)

Associate Professor Daniela Traini

Research Location

Pharmacy Research Theme - Respiratory Disease

Program Type

N/A

Synopsis

Cystic fibrosis (CF) is an inherited disease that affects the lungs. In healthy lungs the mucus present is normally watery, but in CF patients an abnormal gene causes mucus to become thick and sticky, it builds up in the lungs and blocks the airways. This makes it easy for bacteria to grow and leads to repeated serious lung infections. Over time, both these adverse effects can become life threatening. Respiratory failure is in fact the most common cause of death in people with CF. Although mannitol as already been identified as a potential therapeutic agent for the treatment of CF, to the authors knowledge there is no anti-inflammatory on the market that can be delivered conveniently and directly the to the lungs via inhalation. Until now nebulizers have been used as the only alternative to high oral doses (with consequently high risk of side effects), to deliver of anti-inflammatory to the lungs. This therapy is very costly, time consuming for the patient and furthermore mostly inefficacious. The proposed research project aims to devise a novel dual-action formulation to be delivered directly to the site of the disease and that could be efficacious on both the major symptoms presents in CF patients: the build up of thick mucus and the bacterial inflammation.  Delivering both therapeutics in one single dose will have many advantages: having two therapeutic drugs together will relief the CF patients of the immediate symptoms; will increase patient compliance and being a portable device will give CF patient more freedom and independence.

Additional Information

Research Plan: In order to understand the mannitol-antibiotic dry powder system, the project is divided the study into four primary sections:

1. physical characterisation of formulation
2. in vitro characterisation of the synergic dual formulation
3. in vitro human lung epithelium toxicity investigation of the formulation
4. in vivo correlation using an animal model.

Methods and Techniques: Mannitol-antibiotic formulation will be prepared by spray drying method. A series of different concentration ratio of the co-processed dry powder inhaler (DPI) formulations will be prepared for physical-chemical characterisation. Physical-chemical characterisation of the formulation will be analysed. These include the primary particle size, water content, electrostatic charge, the solid or crystalline form, isothermal nanocalorimetry, thermal atomic force microscopy, organic vapour sorption and focused ion beam sectioning. Short and long term chemical stability of the DPI formulations will be investigated using high performance liquid chromatography. Measurements of both aerosol particle size distribution and total dose output will be carried out using a conventional pharmacopoeia impaction methodology for respiratory analysis and a low resistance device, as model testing device. An in vitro model system making use of a human epithelial cell line will be employed to investigate the mechanisms of toxicity of the mannitol-antibiotic formulation on the lung epithelium. The efficacy of this novel synergic formulation will be tested in vivo using a mouse model. Finally, the effect of the mannitol-antibiotic formulation on mucous viscosity will be investigated using an ex vivo rheology test.

Keywords

Cystic fibrosis, Inhalation, Aerosols, Dry Powder Inhalers, Therapeutics & adverse drug effects, Cardiovascular & respiratory diseases, Chronic diseases & ageing, Genetic disorders, Infectious diseases, Genes in biology & medicine, Infection & immunity, Pharmacology & therapeutics, Respiration

Opportunity ID

The opportunity ID for this research opportunity is: 5