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Inhaled ‘fat bubbles’ to deliver lung cancer drug
10 Apr 2023
An inhaled formulation of a next-generation lung cancer drug could help to improve its effectiveness while also reducing side effects for patients.
Lung cancer is the second most common cancer worldwide – and sadly, it is the main cause of cancer death. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers.
Patients with NSCLC are often treated with chemotherapies, which are toxic drugs that indiscriminately kill all rapidly dividing cells in the body. But in recent years, advances in the understanding of the genetic basis of cancer have led to the development of a new generation of targeted cancer drugs designed to exploit specific vulnerabilities in tumour cells.
Erlotinib is a targeted cancer drug used to treat patients with NSCLC with mutations in the epidermal growth factor receptor (EGFR) gene. It is currently delivered as an oral pill – which means it can still accumulate in healthy tissues and cause side effects, such as skin rashes and joint pain.
Developing ways to deliver erlotinib directly into the patient’s lungs could help increase its effectiveness by increasing the concentration of the drug in tumours while also limiting its effects on healthy tissues.
Inhaled formulations
In a new study, published in the International Journal of Pharmaceutics, a team of researchers explored the possibility of packaging erlotinib into tiny ‘fat bubbles’ called liposomes to allow its delivery into the lungs through inhalation.1
The team generated liposomes with different compositions – achieving an encapsulation efficiency for erlotinib of higher than 98% for all vesicles containing phosphatidic acid. They then nebulised the three most promising formulations using two air-jet and two vibrating mesh nebulisers, calculating the aerosol deposition in lungs using computational fluid and particle mechanics tools.
According to the numerical simulations and measurements of liposomal stability, the air-jet nebulisers generated a larger proportion of the aerosol with the ability to penetrate deeper into the lungs. However, drug delivery was likely to be more efficient when the formulation was administered by a vibrating mesh nebuliser due to a higher proportion of intact vesicles. The leakage of the encapsulated drug from its liposomes was lower than 2% for all selected vesicles.
The team used ultrapure water generated from an ELGA PURELAB® laboratory water purification system for these experiments, minimising the risk of introducing contaminants that may affect their results.
Local administration
In this study, researchers explored the feasibility of developing a liposomal formulation of erlotinib that can be delivered directly to the lungs via inhalation. The team demonstrated the encapsulation efficiency of erlotinib in liposomes could be dramatically increased by the presence of phosphatidic acid. They also found that generating aerosols using a vibrating mesh nebuliser is likely to be the most efficient way to deliver the drug into the airways.
These findings suggest that liposomes are a promising drug carrier for the local administration of erlotinib into the lungs of NSCLC patients – which could offer a way to help boost its effectiveness while also preventing side effects.
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Reference:
- Szabová J, Mišík O, Fučík J, Mrázová K, Mravcová L, Elcner J, Lízal F, Krzyžánek V, Mravec F. Liposomal form of erlotinib for local inhalation administration and efficiency of its transport to the lungs. Int J Pharm. 2023 Mar 5;634:122695. doi: 10.1016/j.ijpharm.2023.122695.
Dr Alison Halliday
After completing an undergraduate degree in Biochemistry & Genetics at Sheffield University, Alison was awarded a PhD in Human Molecular Genetics at the University of Newcastle. She carried out five years as a Senior Postdoctoral Research Fellow at UCL, investigating the genes involved in childhood obesity syndrome. Moving into science communications, she spent ten years at Cancer Research UK engaging the public about the charity’s work. She now specialises in writing about research across the life sciences, medicine and health.