Effect of formulation on the stability and aerosol performance of a nebulized antibody

Respaud, Renaud; Marchand, D.; Parent, Christelle; Pelat, Thibaut; Thullier, Philippe; Tournamille, Jean-François; Viaud‐Massuard, Marie‐Claude; Diot, Patrice; Si‐Tahar, Mustapha; Vecellio, Laurent; Heuzé-Vourc’h, Nathalie

doi:10.4161/mabs.29938

Cited by 77 publications

(53 citation statements)

References 27 publications

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“…Surfactants (polysorbates, sorbitan esters, oleic acid, and soy lecithin) are frequently used to prevent aggregate formation, and they work by displacing protein molecules from the ALI [ 46 , 62 ]. Polysorbates are the most commonly used surfactants, and are already being used to preclude aggregation in formulations of intravenously administered antibodies [ 34 ]. Polysorbate 80 has been reported to lead to stabilisation in various inhaled protein formulations including those for granulocyte-colony stimulating factor (G-CSF), lactate dehydrogenase (LDH), tissue plasminogen activator (t-Pa) and aviscumine (recombinant mistletoe lectin) [ 68 ].…”

Section: Approaches To Address the Challenges In Formulating Inhaled mentioning

confidence: 99%

“…The ability of polysorbates and other surfactants to stabilise a protein and hinder aggregate formation is contingent on the protein-to-surfactant ratio. Respaud et al [ 34 ] examined the effects of various antibody and surfactant (polysorbate 20) concentrations to optimise the protein-to-surfactant ratio for a nebulised antibody formulation. The authors determined that high concentrations of either surfactant or protein could minimise the formation of medium and large-sized aggregates, without significantly affecting the volume mean diameter (VMD) of the aerosol cloud, ensuring suitability for inhalation.…”

Section: Approaches To Address the Challenges In Formulating Inhaled mentioning

confidence: 99%

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Developing inhaled protein therapeutics for lung diseases

Matthews

2020

Mol Biomed

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Biologic therapeutics such as protein/polypeptide drugs are conventionally administered systemically via intravenous injection for the treatment of diseases including lung diseases, although this approach leads to low target site accumulation and the potential risk for systemic side effects. In comparison, topical delivery of protein drugs to the lung via inhalation is deemed to be a more effective approach for lung diseases, as proteins would directly reach the target in the lung while exhibiting poor diffusion into the systemic circulation, leading to higher lung drug retention and efficacy while minimising toxicity to other organs. This review examines the important considerations and challenges in designing an inhaled protein therapeutics for local lung delivery: the choice of inhalation device, structural changes affecting drug deposition in diseased lungs, clearance mechanisms affecting an inhaled protein drug’s lung accumulation, protein stability, and immunogenicity. Possible approaches to overcoming these issues will also be discussed.

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Section: Approaches To Address the Challenges In Formulating Inhaled mentioning

confidence: 99%

Section: Approaches To Address the Challenges In Formulating Inhaled mentioning

confidence: 99%

Developing inhaled protein therapeutics for lung diseases

Matthews

2020

Mol Biomed

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“…Formulation may also make it possible to enhance a protein's pharmacological properties. For instance, modified-release formulations (such as microparticles, nanoparticles, or liposomes) might customize pharmacokinetic profiles while avoiding rapid protein degradation [11]. Nevertheless, few FDA-approved excipients for inhalation (i.e.…”

Section: Strategies For Designing Inhaled Protein Therapeuticsmentioning

confidence: 99%

Designing inhaled protein therapeutics for topical lung delivery: what are the next steps?

Bodier-Montagutelli

Mayor

Vecellio

et al. 2018

Expert Opinion on Drug Delivery

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Drug delivery in the airways by inhalation can be used for local and/or systemic action, depending on the ability of the aerosolized drug to cross the air-blood barrier. For proteins, this is partly conditioned by the drug's molecular weight, as well as aerosol characteristics. This editorial focuses on protein inhalation for topical delivery purposes. Even though systemic applications (such as insulin inhalation) are not considered herein, it is worth noting that systemic diffusion following topical delivery may happen in some cases, and provide therapeutic benefit (as is the case for granulocyte-macrophage colony-stimulating factor (GM-CSF)).

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“…Another possible disadvantage of mAbs compared to small molecules is their molecular weight. Most small molecules are hundreds of dalton to a few kilodaltons whereas mAbs are in excess of 100 kDa, which makes inhaled delivery less efficient, but would be less of a problem for systemic delivery [ 51 ].…”

Section: Reviewmentioning

confidence: 99%

Inhaled protein/peptide-based therapies for respiratory disease

2016

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Asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) are all chronic pulmonary diseases, albeit with different etiologies, that are characterized by airflow limitation, chronic inflammation, and abnormal mucus production/rheology. Small synthetic molecule-based therapies are commonly prescribed for all three diseases. However, there has been increased interest in “biologicals” to treat these diseases. Biologicals typically constitute protein- or peptide-based therapies and are often more potent than small molecule-based drugs. In this review, we shall describe the pros and cons of several different biological-based therapies for respiratory disease, including dornase alfa, a recombinant DNAase that reduces mucus viscosity and short palate lung and nasal epithelial clone 1 (SPLUNC1)-derived peptides that treat Na+ hyperabsorption and rebalance CF airway surface liquid homeostasis.

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Effect of formulation on the stability and aerosol performance of a nebulized antibody

Cited by 77 publications

References 27 publications

Developing inhaled protein therapeutics for lung diseases

Developing inhaled protein therapeutics for lung diseases

Designing inhaled protein therapeutics for topical lung delivery: what are the next steps?

Inhaled protein/peptide-based therapies for respiratory disease

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